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1
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Romano A, Zeni N, Caspanello AR, Phillips S, Piano SS, Angeli P. Follow-up post-HCV virological response to DAA in advanced chronic liver disease. Liver Int 2024; 44:3138-3150. [PMID: 39344755 DOI: 10.1111/liv.16113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/05/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024]
Abstract
Direct-acting antivirals (DAA) achieve high virological response rates with minimal side effects for many patients. Despite their significant impact on the progression and epidemiology of hepatitis C virus (HCV) associated liver disease, the global annual incidence of chronic infections is expected to remain relatively constant, averaging 1.42 million new cases each year until 2030. Furthermore, by 2030, there will be a 14-17% increase in end-stage liver disease outcomes such as liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis in adults aged 18 years and over. Although reductions in liver decompensation, HCC occurrence, and mortality have been shown in patients with advanced liver disease who achieved sustained virological response (SVR) with DAA, these benefits may be less significant in those with decompensated liver cirrhosis. This review aims to summarise the impact of the virological response to DAA on liver disease progression and outcomes in patients with advanced chronic liver disease, which appears to be crucial for defining patient-specific follow-up.
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Affiliation(s)
- A Romano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - N Zeni
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - A R Caspanello
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
- Department of Clinical and Experimental Medicine, Unit of Medicine and Hepatology, University of Messina, Messina, Italy
| | - S Phillips
- Institute of Hepatology Foundation for Liver Research London UK, School of Immunology and Microbial Sciences King's College London, London, UK
| | - S S Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
| | - P Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy
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Pearlman BL. Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis. Dig Dis Sci 2024; 69:1551-1561. [PMID: 38580885 DOI: 10.1007/s10620-024-08393-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/16/2024] [Indexed: 04/07/2024]
Abstract
Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.
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Affiliation(s)
- Brian L Pearlman
- Center for Hepatitis C, Wellstar Atlanta Medical Center, 285 Boulevard NE, Suite 525, Atlanta, GA, 30312, USA.
- Medical College of Georgia, Augusta, GA, USA.
- Emory School of Medicine, Atlanta, GA, USA.
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3
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Flamm S, Lawitz E, Borg B, Charlton M, Landis C, Reddy KR, Shiffman M, Alsina A, Chang C, Ravendhran N, Hernandez C, Hézode C, Scherbakovsky S, Mercier RC, Samuel D. Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis. Viruses 2023; 15:2026. [PMID: 37896803 PMCID: PMC10611233 DOI: 10.3390/v15102026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 10/29/2023] Open
Abstract
A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.
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Affiliation(s)
- Steven Flamm
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA
| | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX 78215, USA
| | - Brian Borg
- Southern Therapy and Advanced Research LLC, Jackson, MS 39216, USA
| | | | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA 98101, USA
| | - K. Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Mitchell Shiffman
- Bon Secours Mercy Health, Liver Institute of Virginia, Richmond, VA 23226, USA
| | - Angel Alsina
- Tampa General Medical Group, Tampa, FL 33609, USA
| | - Charissa Chang
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | | | | | | | | | | | - Didier Samuel
- Centre Hépatobiliaire, Hôpital Paul-Brousse, Inserm Research Unit 1193, Université Paris-Saclay, 94800 Villejuif, France
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Luan CH, Su PS, Chu CJ, Lin CC, Su CW, Lee SD, Wang YJ, Lee FY, Huang YH, Hou MC. Residual risk of hepatocellular carcinoma development for chronic hepatitis C patients treated by all oral direct-acting antivirals with sustained virological response. J Chin Med Assoc 2023; 86:795-805. [PMID: 37466658 DOI: 10.1097/jcma.0000000000000965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan. METHODS Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models. RESULTS The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047). CONCLUSION Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.
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Affiliation(s)
- Chih-Hsuan Luan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Pin-Shuo Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Muquith M, Espinoza M, Hsiehchen D. Reversal of Hepatic Dysfunction After Exceptional Responses to Lenvatinib. J Gastrointest Cancer 2023; 54:982-985. [PMID: 35939228 DOI: 10.1007/s12029-022-00852-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/21/2022] [Indexed: 10/15/2022]
Affiliation(s)
- Maishara Muquith
- University of Texas Southwestern Medical School, Dallas, TX, 75390, USA
| | - Magdalena Espinoza
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - David Hsiehchen
- Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
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Ishigami M, Honda T, Ishizu Y, Imai N, Ito T, Yamamoto K, Kawashima H. Significance of pretreatment alpha-fetoprotein in patients with compensated severe fibrosis after hepatitis C viral eradication. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023. [PMID: 36715458 DOI: 10.1002/jhbp.1309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/14/2023] [Accepted: 01/17/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND We aimed to investigate the factors associated with improvement of liver functional reserve after sustained virological response using interferon-free, direct-acting antiviral combination treatment in patients with compensated, severe fibrosis. METHODS Between September 2014 and April 2020, 492 patients received direct-acting antiviral combination treatment in our hospital. Among them, 173 patients who had severe fibrosis based on a fibrosis-4 index ≥3.25, showed sustained virological response after treatment. We investigated the dynamic change in albumin-bilirubin score and the baseline factors associated with its improvement, 48 weeks after treatment. RESULTS The baseline significant factors associated with albumin-bilirubin ≦ -0.5 were lower albumin (HR: 15.625, 95% CI: 4.273-58.824, P < .001), higher hepatitis C virus RNA (HR: 4.995, 95% CI: 1.882-13.260, P = .001), and higher alpha-fetoprotein (HR: 1.033, 95% CI: 1.011-1.055, P = .003). Patients with alpha-fetoprotein ≧10 ng/mL showed significant improvement of albumin-bilirubin score from baseline to 48 weeks after treatment compared to those with alpha-fetoprotein <10 ng/mL (P < .001). CONCLUSIONS Baseline serum alpha-fetoprotein might be a predictive factor for improvement of liver function after sustained virological response in patients with severe fibrosis.
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Affiliation(s)
- Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
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Meunier L, Belkacemi M, Pageaux GP, Radenne S, Vallet-Pichard A, Houssel-Debry P, Duvoux C, Botta-Fridlund D, de Ledinghen V, Conti F, Anty R, Di Martino V, Debette-Gratien M, Leroy V, Gerster T, Lebray P, Alric L, Abergel A, Dumortier J, Besch C, Montialoux H, Samuel D, Duclos-Vallée JC, Coilly A. Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years? Viruses 2022; 15:137. [PMID: 36680177 PMCID: PMC9865729 DOI: 10.3390/v15010137] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. METHODS An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. RESULTS A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child-Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. CONCLUSIONS DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.
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Affiliation(s)
- Lucy Meunier
- Montpellier Saint Eloi University Hospital, 80 Avenue Augustin Fliche, 34090 Montpellier, France
| | | | - George Philippe Pageaux
- Montpellier Saint Eloi University Hospital, 80 Avenue Augustin Fliche, 34090 Montpellier, France
| | - Sylvie Radenne
- Croix-Rousse Hospital, Lyon University Hospital, 103 Grande Rue de la Croix-Rousse, 69004 Lyon, France
| | - Anaïs Vallet-Pichard
- Cochin Hospital, Public Hospitals of Paris, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | | | - Christophe Duvoux
- Henri-Mondor University Hospital, Public Hospitals of Paris, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
| | - Danielle Botta-Fridlund
- Marseille Public Hospital, Timone University Hospital, 264 Rue Saint Pierre, 13005 Marseille, France
| | - Victor de Ledinghen
- Hepatology and Liver Transplantation Unit, Haut-Lévêque Hospital, Bordeaux University Hospital, 33600 Pessac, France
| | - Filomena Conti
- Pitié-Salpêtrière University Hospital, Public Hospitals of Paris, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
| | - Rodolphe Anty
- Archet 2 Hospital, Nice University Hospital, 151 Route de Saint-Antoine, 06200 Nice, France
| | - Vincent Di Martino
- Besançon Regional University Hospital, 3 Boulevard Alexandre Fleming, 25000 Besançon, France
| | | | - Vincent Leroy
- Service d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38700 La Tronche, France
| | - Theophile Gerster
- Service d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38700 La Tronche, France
| | - Pascal Lebray
- Pitié-Salpêtrière University Hospital, Public Hospitals of Paris, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
| | - Laurent Alric
- Rangueil Hospital, Toulouse 3 University Hospital, 31000 Toulouse, France
| | - Armand Abergel
- Gabriel-Montpied Hospital, Clermont-Ferrand University Hospital, 58 Rue Montalembert, 63000 Clermont-Ferrand, France
| | - Jérôme Dumortier
- Edouard Herriot Hospital, Lyon University Hospital, 5 Place d’Arsonval, 69003 Lyon, France
| | - Camille Besch
- Hautepierre Hospital, Strasbourg University Hospital, 1 Avenue Molière, 67200 Strasbourg, France
| | - Helene Montialoux
- Rouen University Hospital, 37 Boulevard Gambetta, 76000 Rouen, France
| | - Didier Samuel
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
| | - Jean-Charles Duclos-Vallée
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
| | - Audrey Coilly
- Paul-Brousse Hospital, Public Hospsitals of Paris, 12 Avenue Paul Vaillant Couturier, FHU Hépatinov, 94800 Villejuif, France
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Nguyen VH, Kam L, Yeo YH, Huang DQ, Henry L, Cheung R, Nguyen MH. Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States. JAMA Netw Open 2022; 5:e2245424. [PMID: 36477481 PMCID: PMC9856330 DOI: 10.1001/jamanetworkopen.2022.45424] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse. OBJECTIVE To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US. MAIN OUTCOMES AND MEASURES The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression. RESULTS A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90). CONCLUSIONS AND RELEVANCE In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.
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Affiliation(s)
- Vy H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Leslie Kam
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Daniel Q. Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, California
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9
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Pereira GH, Peixoto HR, Giusti ML, Souza ML, Victor LB, Fernandes F, Perez RM, Villela-Nogueira CA. Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study. Braz J Infect Dis 2022; 26:102697. [PMID: 36037847 PMCID: PMC9485045 DOI: 10.1016/j.bjid.2022.102697] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/13/2022] [Accepted: 08/05/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.
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Affiliation(s)
- Gustavo H Pereira
- Hospital Federal de Bonsucesso, Serviço de Gastroenterologia e Hepatologia, Rio de Janeiro, RJ, Brazil; Universidade Estácio de Sá, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
| | - Helena R Peixoto
- Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
| | - Mariana L Giusti
- Universidade Estácio de Sá, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
| | - Mariana L Souza
- Universidade Estácio de Sá, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
| | - Livia B Victor
- Hospital Federal de Bonsucesso, Serviço de Gastroenterologia e Hepatologia, Rio de Janeiro, RJ, Brazil; Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Clínica Médica, Rio de Janeiro, RJ, Brazil
| | - Flávia Fernandes
- Hospital Federal de Bonsucesso, Serviço de Gastroenterologia e Hepatologia, Rio de Janeiro, RJ, Brazil; Universidade Estácio de Sá, Faculdade de Medicina, Rio de Janeiro, RJ, Brazil
| | - Renata M Perez
- D'Or Research Institute, Rio de Janeiro, RJ, Brazil; Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Serviço de Hepatologia, Rio de Janeiro, RJ, Brazil
| | - Cristiane A Villela-Nogueira
- Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Serviço de Hepatologia, Rio de Janeiro, RJ, Brazil.
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10
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Kuntzen C, Bagha Z. The Use of Hepatitis C Virus-Positive Organs in Hepatitis C Virus-Negative Recipients. Clin Liver Dis 2022; 26:291-312. [PMID: 35487612 DOI: 10.1016/j.cld.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The use of hepatitis C virus (HCV) -positive organs in HCV-negative recipients with posttransplant antiviral treatment has increasingly been studied since the introduction of new direct-acting antivirals. This article reviews existing experience in liver and kidney transplant. Fifteen studies with 218 HCV D+/R- liver transplants, with 182 from viremic donors, show a sustained viral response for 12 weeks (SVR12) rate of 99.5%. Nine studies involving 204 HCV donor-positive recipient-negative kidney transplant recipients had an SVR12 rate of 99.5%. Complications are infrequent. Preemptive treatment in kidney transplant of for only 4 weeks or even 4 days showed surprising success rates.
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Affiliation(s)
- Christian Kuntzen
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA.
| | - Zohaib Bagha
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA
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11
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Pretransplant Hepatitis C Virus Treatment Decreases Access to High-quality Livers. Transplant Direct 2021; 7:e684. [PMID: 34549082 PMCID: PMC8440014 DOI: 10.1097/txd.0000000000001127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 11/27/2022] Open
Abstract
Background Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes. Methods This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data. Results Among pre-LT untreated recipients, 95% were willing to accept an HCV+ donor, and 44.8% received a positive HCV antibody and nucleic acid amplification test (NAT) liver. Among pre-LT treated recipients, 5% were willing to accept an HCV+ donor, and 100% received a negative HCV antibody and NAT liver. The median calculated model for end-stage liver disease at transplant was similar between pre-LT untreated (13, IQR = 9-22) and treated recipients (11, IQR = 8-14) (P = 0.1). Pre-LT treated recipients received livers from older (47 y old versus 37, P < 0.01) and higher body mass index donors (30.2 versus 26.6; P = 0.04) and spent longer on the waiting list (319 d 180, P < 0.001). Unadjusted post-LT mortality at 1 year was higher in the pre-LT treated recipients (14.6% versus 3.5%, P = 0.02). After adjusting for recipient factors, pre-LT treated recipients trended toward a 3.9 times higher risk of mortality compared with the pre-LT untreated recipients (adjusted hazard ratio = 0.973.8615.4) (P = 0.06). Conclusions Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival.
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12
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Berkan-Kawińska A, Piekarska A, Janczewska E, Lorenc B, Tudrujek-Zdunek M, Tomasiewicz K, Berak H, Horban A, Zarębska-Michaluk D, Pabjan P, Buczyńska I, Pazgan-Simon M, Dybowska D, Halota W, Pawłowska M, Klapaczyński J, Mazur W, Czauż-Andrzejuk A, Socha Ł, Laurans Ł, Garlicki A, Sitko M, Jaroszewicz J, Citko J, Dobracka B, Krygier R, Białkowska-Warzecha J, Tronina O, Belica-Wdowik T, Baka-Ćwierz B, Flisiak R. Real-world effectiveness and safety of direct-acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi-Ter2 Study. Liver Int 2021; 41:1789-1801. [PMID: 33655628 DOI: 10.1111/liv.14858] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 01/30/2021] [Accepted: 02/18/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.
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Affiliation(s)
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Łódź, Poland
| | - Ewa Janczewska
- Medical University of Silesia, School of Public Health in Bytom, Department of Basic Medical Sciences, Bytom, Poland.,ID Clinic, Hepatology Outpatient Department, Mysłowice, Poland
| | - Beata Lorenc
- Department of Infectious Diseases, Pomeranian Center of Infectious Diseases, Medical University of Gdansk, Gdansk, Poland
| | | | | | - Hanna Berak
- Hospital for Infectious Diseases, Warsaw Medical University, Warszawa, Poland
| | - Andrzej Horban
- Hospital for Infectious Diseases, Warsaw Medical University, Warszawa, Poland
| | - Dorota Zarębska-Michaluk
- Department of Infectious Disease, Voivodeship Hospital, Jan Kochanowski University, Kielce, Poland
| | - Paweł Pabjan
- Department of Infectious Disease, Voivodeship Hospital, Jan Kochanowski University, Kielce, Poland
| | - Iwona Buczyńska
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wrocław, Poland
| | - Monika Pazgan-Simon
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wrocław, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of Internal Affairs and Administration, Warszawa, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland.,Multidisciplinary Regional Hospital, Gorzów Wielkopolski, Poland
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Collegium Medicum, Jagiellonian University, Kraków, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Collegium Medicum, Jagiellonian University, Kraków, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | | | | | - Rafał Krygier
- NZOZ Gemini, Infectious Diseases and Hepatology Outpatient Clinic, Zychlin, Poland
| | | | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warszawa, Poland
| | - Teresa Belica-Wdowik
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - Barbara Baka-Ćwierz
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
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13
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Ejtehadi F, Farahvashi P, Shamsaeefar A, Niknam R, Sivandzadeh GR, Aminlari L, Motazedian N, Kazemi K, Nikoupour H, Nikeghbalian S, Eghlimi H, Taghavi A, Fattahi M, Bagheri Lankarani K, Malek-Hosseini SA. Clinical Course and Outcome of Liver Transplantation in Patients with Hepatitis C in Iran. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.108405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Hepatitis C is one of the most common causes of end-stage liver disease and liver transplant worldwide. In recent years, with the rapid advances in the treatment of hepatitis C by direct-acting antiviral drugs (DAAs), the clinical course of the disease as well as liver transplantation have had significant improvement. Also, DAAs have completely replaced interferon-based regimens in the treatment and prevention of HCV recurrence after liver transplant. Objectives: This is the first study that aimed to investigate the clinical course of liver transplantation in patients with hepatitis C in Iran. Methods: This retrospective study was conducted on patients with HCV liver transplantation within five years (2012 - 2017) with the age range of 18 to 65 years at Shiraz Organ Transplant Center. All demographic and clinical data were recorded. Pre-transplant viral load, disease recurrence, graft rejection, and mortality rate were the most important indices in this study. Results: Among 55 transplant patients, 49% had received hepatitis C treatment before liver transplantation and interferon-based regimens were more prevalent. Besides, HCV genotype 3, followed by genotype 1, was the most prevalent one. A liver biopsy was performed in patients with elevated liver enzyme levels. The numbers of patients with HCV recurrence at 2, 6, 12, and 24-month intervals were three, two, zero, and two patients, respectively. At these time intervals, eight, eight, one, and three cases of acute graft rejection were found, respectively. Eight patients died with a one-year survival rate of 85%. Sepsis and infectious complications were the most leading causes of death. Conclusions: This study is the first study of liver transplant patients with hepatitis C in Iran. In the five-year study period, rapid development was made in the treatment of HCV patients. It led to the introduction of DAAs, which replaced interferon-based therapies. The results of this study indicated the high success rate of liver transplantation in patients with hepatitis C in Iran. The results of this study could be used to compare the efficacy of DAAs in future research.
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14
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Lourenço MS, Zitelli PMY, Cunha-Silva M, Oliveira AIN, de Lima RGR, Evandro de Oliveira S, Oliveira CP, Sevá-Pereira T, Carrilho FJ, Pessoa MG, Mazo DF. Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study. Clinics (Sao Paulo) 2021; 76:e3186. [PMID: 34817045 PMCID: PMC8579851 DOI: 10.6061/clinics/2021/e3186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 10/04/2021] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVES Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.
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Affiliation(s)
- Mariana Sandoval Lourenço
- Divisao de Gastroenterologia (Gastrocentro), Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BR
| | - Patricia Momoyo Y. Zitelli
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Marlone Cunha-Silva
- Divisao de Gastroenterologia (Gastrocentro), Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BR
| | - Arthur Ivan N. Oliveira
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Roque Gabriel Rezende de Lima
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Souza Evandro de Oliveira
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Claudia P. Oliveira
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Tiago Sevá-Pereira
- Divisao de Gastroenterologia (Gastrocentro), Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BR
| | - Flair J. Carrilho
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Mario G. Pessoa
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
| | - Daniel F. Mazo
- Divisao de Gastroenterologia (Gastrocentro), Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BR
- Divisao de Gastroenterologia e Hepatologia Clinica, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
- Corresponding author. E-mail:
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15
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Mendizabal M, Piñero F, Ridruejo E, Herz Wolff F, Anders M, Reggiardo V, Ameigeiras B, Palazzo A, Alonso C, Schinoni MI, Videla Zuain MG, Tanno F, Figueroa S, Santos L, Peralta M, Soza A, Vistarini C, Adrover R, Fernández N, Perez D, Hernández N, Estepo C, Bruno A, Descalzi V, Sixto M, Borzi S, Cocozzella D, Zerega A, de Araujo A, Varón A, Rubinstein F, Cheinquer H, Silva M. Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents. Clin Gastroenterol Hepatol 2020; 18:2554-2563.e3. [PMID: 32113892 DOI: 10.1016/j.cgh.2020.02.044] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 01/23/2020] [Accepted: 02/22/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina.
| | - Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
| | - Ezequiel Ridruejo
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina; Centro de Educación Médica e Investigaciones Clínicas, CEMIC, Ciudad de Buenos Aires, Argentina
| | | | | | | | | | | | - Cristina Alonso
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
| | | | | | | | | | | | - Mirta Peralta
- Hospital Francisco J. Muñiz, Ciudad de Buenos Aires, Argentina
| | - Alejandro Soza
- Hospital Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | | | | | | | | | - Claudio Estepo
- Hospital Cosme Argerich, Ciudad de Buenos Aires, Argentina
| | - Andres Bruno
- Hospital Cosme Argerich, Ciudad de Buenos Aires, Argentina
| | | | | | | | | | | | | | - Adriana Varón
- Hospital Francisco J. Muñiz, Ciudad de Buenos Aires, Argentina
| | | | - Hugo Cheinquer
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Marcelo Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
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16
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Debnath P, Chandnani S, Rathi P, Nair S, Junare P, Udgirkar S, Singh A, Contractor Q. A new model to predict response to direct-acting antiviral therapy in decompensated cirrhotics due to hepatitis C virus. Clin Exp Hepatol 2020; 6:253-262. [PMID: 33145432 PMCID: PMC7592091 DOI: 10.5114/ceh.2020.99525] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023] Open
Abstract
AIM of the study: Decompensated hepatitis C virus (HCV) cirrhosis is a difficult to treat cohort, and there is no gold standard predictor of response to direct-acting antiviral (DAA) therapy. We conducted this study to look for factors responsible for improvement in post-therapy status, i.e. attainment of Child-Turcotte-Pugh (CTP) class A from B or C, and devise a new model to predict post-therapy response. MATERIAL and methods: Prospective analysis of data from decompensated HCV cirrhotics was done and association of each parameter with patient outcomes at 36 weeks after treatment was assessed. RESULTS 34 patients (54.8%) attained CTP class A after treatment. Factors that were independently associated with disease outcome included albumin (odds ratio [OR] = 4.84, 95% confidence interval [CI]: 1.43-20.15, p = 0.018), alanine transaminase (ALT) (OR = 1.02, 95% CI: 1-1.04, p = 0.049), bilirubin (OR = 0.41, 95% CI: 0.2-0.75, p = 0.007) and estimated glomerular filtration rate (eGFR) (OR = 1.03, 95% CI: 1.0-1.06, p = 0.045). On multivariate analysis, bilirubin was significantly associated with treatment outcome (OR = 0.28, 95% CI: 0.1-0.64, p = 0.006). A composite model was devised using demographic, biochemical, and clinical features, which has sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 67.86%, 79.41%, 73.08%, 75%, and 73.63% respectively in predicting response to therapy. Only 7.6% of patients with a Model for End-Stage Liver Disease (MELD) score > 15 and none of the patients with CTP class C met the primary end-point of our study. CONCLUSIONS 55% of our cohort met the primary end-point at 36 weeks. Patients with CTP class C and a MELD score > 15 should be referred for liver transplantation followed by DAA therapy. Our model was good at predicting improvement in post-therapy liver function.
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Affiliation(s)
| | | | - Pravin Rathi
- TNMC & BYL Nair Charitable Hospital, Mumbai, India
| | - Sujit Nair
- TNMC & BYL Nair Charitable Hospital, Mumbai, India
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17
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Verna EC, Morelli G, Terrault NA, Lok AS, Lim JK, Di Bisceglie AM, Zeuzem S, Landis CS, Kwo P, Hassan M, Manns MP, Vainorius M, Akushevich L, Nelson DR, Fried MW, Reddy KR. DAA therapy and long-term hepatic function in advanced/decompensated cirrhosis: Real-world experience from HCV-TARGET cohort. J Hepatol 2020; 73:540-548. [PMID: 32243960 DOI: 10.1016/j.jhep.2020.03.031] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 02/27/2020] [Accepted: 03/19/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. METHODS Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. RESULTS A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10-39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9-26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (-0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of <10 was achieved in 25%. CONCLUSION In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. CLINICALTRIALS.GOV: NCT01474811. LAY SUMMARY Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.
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Affiliation(s)
| | - Giuseppe Morelli
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL
| | | | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Joseph K Lim
- Viral Hepatitis Program, Yale University School of Medicine, New Haven, CT
| | - Adrian M Di Bisceglie
- Chief of Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO
| | - Stefan Zeuzem
- Department of Medicine, Goethe University Hospital, Frankfurt, Germany
| | - Charles S Landis
- Department of Gastroenterology, University of Washington, Seattle, WA
| | - Paul Kwo
- Department of Hepatology, Stanford University, Stanford, CA
| | - Mohamed Hassan
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota, Minneapolis, MN
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Monika Vainorius
- Biometrics and Data Quality HCV-TARGET Data Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Lucy Akushevich
- University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - David R Nelson
- Department of Medicine, University of Florida, Gainesville, FL
| | - Michael W Fried
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - K Rajender Reddy
- Professor, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA.
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18
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Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020; 46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalization, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
| | - Radhika Venugopal
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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19
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Bhuvanakrishna T, Wakefield S. A commentary on "Liver transplantation for Hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study". Int J Surg 2020; 76:62-63. [PMID: 32105896 DOI: 10.1016/j.ijsu.2020.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 02/14/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Thakshyanee Bhuvanakrishna
- Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust, Heath Road, Ipswich, IP4 5PD, United Kingdom.
| | - Simon Wakefield
- Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust, Heath Road, Ipswich, IP4 5PD, United Kingdom
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20
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Khan AS, Adams N, Vachharajani N, Dageforde L, Wellen J, Shenoy S, Crippin JS, Doyle MB, Chapman WC. Liver transplantation for hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study. Int J Surg 2020; 75:84-90. [PMID: 32014598 DOI: 10.1016/j.ijsu.2020.01.145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 01/10/2020] [Accepted: 01/23/2020] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT). METHODS Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014-2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) RESULTS: 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for "condition improved" (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's. CONCLUSIONS DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.
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Affiliation(s)
- Adeel S Khan
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Nathaniel Adams
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Neeta Vachharajani
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - LeighAnne Dageforde
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Jason Wellen
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Surendra Shenoy
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Jeffrey S Crippin
- Department of Medicine, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - Majella B Doyle
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
| | - William C Chapman
- Section of Transplant Surgery, Washington University St. Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO, 63110, USA.
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21
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Wu SH, Loong CC, Chu CJ, Su CW, Lin CC, Hsia CY, Liu C, Lee SD, Wang YJ, Lee FY, Linb NC, Chen CY, Huang YH, Hou MC. Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation. J Chin Med Assoc 2020; 83:18-24. [PMID: 31714442 DOI: 10.1097/jcma.0000000000000222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.
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Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chinsu Liu
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Niang-Cheng Linb
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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22
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Zeuzem S. [Chronic hepatitis C : Standard treatment and remaining challenges]. Internist (Berl) 2019; 59:528-535. [PMID: 29696303 DOI: 10.1007/s00108-018-0429-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND Among patients with chronic hepatitis C, 20-30% develop cirrhosis and its complications within 30 years. The antiviral treatment of hepatitis C has become interferon-free, with resulting improvements in sustained virological response rates, safety and tolerability and a shorter duration of treatment. OBJECTIVE The mechanism of action of available drugs and current treatment recommendations. MATERIAL AND METHODS This review is based on relevant publications retrieved by a selective literature search and particularly on studies and reviews concerning the course and treatment of hepatitis C. RESULTS The available drugs for interferon-free antiviral treatment of hepatitis C include inhibitors of the RNA-dependent RNA polymerase, NS3/4A protease, and NS5A protein of the hepatitis C virus (HCV), and ribavirin. Typically, two specific inhibitors are given in combination and the usual duration of treatment is 8-12 weeks. The antiviral drugs differ in their genotypic effectiveness and resistance barriers. The appropriate drug(s) should be chosen in consideration of the patient's hepatic and renal function and potential drug-drug interactions. All approved anti-HCV drugs are safe and well-tolerated and result in sustained virological response rates above 95%. CONCLUSION All patients with hepatitis C, whatever their disease stage, can achieve a sustained eradication of HCV using a combination of drugs with direct antiviral activity. Viral eradication is associated with a better quality of life and with lower morbidity and mortality.
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Affiliation(s)
- S Zeuzem
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland.
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23
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Mar J, Martínez-Baz I, Ibarrondo O, Juanbeltz R, San Miguel R, Casado I, O'Leary A, Castilla J. Survival and clinical events related to end-stage liver disease associated with HCV prior to the era of all oral direct-acting antiviral treatments. Expert Rev Gastroenterol Hepatol 2019; 13:699-708. [PMID: 28946785 DOI: 10.1080/17474124.2017.1383155] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Background: The aim of this study was to describe the natural long-term course of end-stage liver disease associated with chronic hepatitis C (HCV) infection by measuring survival and complication rates in the era prior to the arrival of new direct-acting antiviral (DAA) drugs. Methods: A retrospective population-based cohort study was designed to establish the follow-up of patients hospitalized for a decompensated cirrhotic event or hepatocellular carcinoma using electronic records from hospital discharge databases from 2009 to 2015. Their survival was compared with a sex, age and non-liver mortality excess matched simulation of the general Spanish population. Results: A total of 253 patients were included in the study. Among those with decompensated cirrhosis (n = 151) the hospital admission rate was 1.88 per patient-year with a mortality rate of 0.16 per patient-year. Mean survival was 4.10 years for patients with decompensated cirrhosis, and 1.75 for non-transplanted hepatocellular carcinoma, compared to 18.39 years for the general population. Conclusion: Our results show the complexity and rapid progression of end-stage liver disease associated with HCV infection. The considerable loss of life expectancy associated with the development of decompensated cirrhosis in patients with chronic HCV infection in the absence of viral clearance through treatment is acutely evident.
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Affiliation(s)
- Javier Mar
- a Clinical Management Unit , Alto Deba Hospital , Mondragon , Spain.,b Health Services Research on Chronic Patients Network (REDISSEC) , Kronikgune Group , Bilbao , Spain.,c Biodonostia Health Research Institute , San Sebastian-Donostia , Spain
| | - Iván Martínez-Baz
- d Instituto de Salud Pública de Navarra , Pamplona , Spain.,e Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain.,f CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain
| | - Oliver Ibarrondo
- g AP-OSI Research Unit, Alto Deba Integrated Health Care Organization , Mondragon , Spain
| | - Regina Juanbeltz
- e Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain.,f CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain.,h Department of Pharmacy , Complejo Hospitalario de Navarra , Pamplona , Spain
| | - Ramón San Miguel
- e Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain.,h Department of Pharmacy , Complejo Hospitalario de Navarra , Pamplona , Spain
| | - Itziar Casado
- d Instituto de Salud Pública de Navarra , Pamplona , Spain.,e Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain.,f CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain
| | - Aisling O'Leary
- i National Centre for Pharmacoeconomics , St Jame's Hospital , Dublin , Ireland.,j School of Pharmacy , Royal College of Surgeons in Ireland , Dublin , Ireland
| | - Jesús Castilla
- d Instituto de Salud Pública de Navarra , Pamplona , Spain.,e Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain.,f CIBER Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain
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24
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Current and forthcoming perspectives in linkage to care of hepatitis C virus infection: Assessment of an Italian focus group. Dig Liver Dis 2019; 51:915-921. [PMID: 31031174 DOI: 10.1016/j.dld.2019.03.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/06/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) remains a significant public health problem and is one of the major causes of chronic liver disease worldwide. In recent years many new tools to facilitate widespread HCV screening and new therapeutic options with excellent efficacy and tolerability profiles and cost lowering policies have become available. To fully utilise these new tools, the link between local and specialist centres for the management of HCV infection must be reinforced. In order to GAIN further insight into these aspects, with a particular focus on the Italian scenario, a group of experts met to discuss relevant aspects and open issues on chronic HCV. As a summary of that meeting, the following aspects are here overviewed: (i) global situation of HCV; (ii) screening, diagnosis and indications for the treatment of HCV; (iii) the Italian situation of HCV referrals; (iv) 'hard to reach' patients; (v) treatment of HCV with extrahepatic manifestations; (vi) treatment of patients with advanced cirrhosis. It is the intention of the expert panel to further promote widespread screening and eradication policies that should be accompanied by greater interaction, by attempting to involve all healthcare providers in an organised process to facilitate linkage to care of patients with HCV infections.
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25
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Ekpanyapong S, Reddy KR. Hepatitis C virus therapy in advanced liver disease: Outcomes and challenges. United European Gastroenterol J 2019; 7:642-650. [PMID: 31210942 PMCID: PMC6545711 DOI: 10.1177/2050640619840149] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/26/2019] [Indexed: 01/06/2023] Open
Abstract
While for many years investigators had worked on highly effective direct-acting antiviral agent (DAA) therapy, we are now encountering challenges on the appropriate timing of DAA therapy in patients with decompensated cirrhosis. Improvement in hepatic function and quality of life can be achieved following successful therapy but not in all patients. Predictors of improvement or failure to improve have been noted but these are currently not robust enough to ubiquitously apply them to clinical practice. The lowest probability of improvement in hepatic function and avoidance of Model for End-stage Liver Disease (MELD) "purgatory" appears to be in those with MELD >20 while the more likely scenario of improvements is in those with MELD <15. Ideally, patients with a MELD score >20 should be transplanted first and treated for hepatitis C virus (HCV) infection after liver transplantation (LT). Those with MELD score <15 should be considered readily for treatment while in those with MELD of 15-20, treatment has to be individualized with full discussion of the pros and cons of treating them pre- or post-LT. However, it is to be appreciated that the majority of patients with decompensated cirrhosis across the world may not be eligible for liver transplant or may not have access to LT; thus, these patients should be considered for HCV therapy with the hope and expectation that they still gain variable degrees of benefit from successful DAA therapy.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
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26
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Al-Judaibi B, Thomas B, Wong P, Benmassaoud A, Chen JH, Dokus MK, Hussaini T, Bilodeau M, Burak KW, Marotta P, Yoshida EM. Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience. Ann Hepatol 2019; 17:437-443. [PMID: 29735784 DOI: 10.5604/01.3001.0011.7388] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. MATERIAL AND METHODS A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. RESULTS 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. CONCLUSIONS SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list .
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Affiliation(s)
- Bandar Al-Judaibi
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Benson Thomas
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Philip Wong
- Department of Medicine, Division of Gastroenterology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada
| | - Amine Benmassaoud
- Department of Medicine, Division of Gastroenterology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada
| | - Jo-Hua Chen
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada
| | - M Katherine Dokus
- Department of Medicine, Division of Gastroenterology, University of Rochester, Rochester, New York, United States of America
| | - Trana Hussaini
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada
| | - Marc Bilodeau
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada
| | - Kelly W Burak
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Alberta, Canada
| | - Paul Marotta
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Eric M Yoshida
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada
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27
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Wei L, Huang YH. Long-term outcomes in patients with chronic hepatitis C in the current era of direct-acting antiviral agents. Expert Rev Anti Infect Ther 2019; 17:311-325. [PMID: 30856022 DOI: 10.1080/14787210.2019.1588112] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Within the past decade, antiviral treatment for chronic hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based regimens to IFN-free oral direct-acting antiviral agents (DAAs). However, data on long-term outcomes in HCV patients treated by DAAs are limited and complex. Areas covered: Original studies and meta-analyses reporting data on the impacts of IFN - and DAA-based treatments on late relapse, liver fibrosis/cirrhosis, decompensation progression, hepatocellular carcinoma (HCC) occurrence and recurrence, need for liver transplantation, mortality, and other topics of interest for long-term observation of HCV patients treated with DAAs. Articles published up to June 2018, and proceedings from annual meetings of major international liver diseases associations (from 2015 to June 2018) were reviewed. Relevant references from selected papers were also reviewed. Expert opinion: In HCV patients treated with DAAs or IFN-based regimens, late relapse beyond 12 weeks after completion of treatment is uncommon. Results from long-term follow-up studies suggest responders to antiviral treatment achieve benefits on regression of fibrosis/cirrhosis, decreasing risk of progression to liver decompensation, reductions in the need for liver transplantation and mortality. Well-designed studies with robust comparisons are needed to determine the effect of DAAs on the recurrence of HCC in the future.
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Affiliation(s)
- Lai Wei
- a Center for Hepatology Pancrease Disease, Beijing Tsinghua Changgung Hospital , Tsinghua University , Beijing.,b Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease , Peking University People's Hospital , Beijing
| | - Yi-Hsiang Huang
- c Division of Gastroenterology and Hepatology , Taipei Veterans General Hospital , Taipei
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28
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Macías J, Granados R, Téllez F, Merino D, Pérez M, Morano LE, Palacios R, Paniagua M, Frías M, Merchante N, Pineda JA. Similar recovery of liver function after response to all-oral HCV therapy in patients with cirrhosis with and without HIV coinfection. J Viral Hepat 2019; 26:16-24. [PMID: 30141222 DOI: 10.1111/jvh.12990] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 06/14/2018] [Accepted: 07/31/2018] [Indexed: 12/12/2022]
Abstract
Among patients with cirrhosis, recovery of liver function after SVR to all-oral direct-acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV-monoinfected and HIV/HCV-coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR-DAA and GEHEP-MONO cohorts were selected if they had SVR12 to all-oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child-Pugh-Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV-infected individuals and in 82 (57%) HIV/HCV-coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV-monoinfected patients and in 33 (13%) HIV/HCV-coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03-4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004-3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2-5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3-12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV-monoinfected and HIV/HCV-coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.
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Affiliation(s)
- Juan Macías
- Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain
| | - Rafael Granados
- Infectious Diseases Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Gran Canaria, Spain
| | - Francisco Téllez
- Infectious Diseases and Microbiology Unit, Hospital Universitario de Puerto Real, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), Puerto Real, Spain
| | - Dolores Merino
- Infectious Diseases Unit, Hospital Juan Ramón Jiménez, Huelva, Spain
| | | | - Luis E Morano
- Infectious Diseases Unit, Hospital Universitario Álvaro Cunqueiro, Vigo, Spain
| | - Rosario Palacios
- Infectious Diseases Unit, Hospital Universitario Virgen de la Victoria, Malaga, Spain
| | - María Paniagua
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena, Seville, Spain
| | - Mario Frías
- Instituto Maimonides de Investigación Biomedica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Nicolás Merchante
- Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain
| | - Juan A Pineda
- Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain
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Shoreibah M, Romano J, Sims OT, Guo Y, Jones D, Venkata K, Kommineni V, Orr J, Fitzmorris P, Massoud OI. Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients. J Clin Transl Hepatol 2018; 6:391-395. [PMID: 30637216 PMCID: PMC6328736 DOI: 10.14218/jcth.2018.00026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/17/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022] Open
Abstract
Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John Romano
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar T. Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Yuqi Guo
- School of Social Work, University of Alabama, Tuscaloosa, AL, USA
| | - DeAnn Jones
- Department of Pharmacology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Krishna Venkata
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Vishnu Kommineni
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jordan Orr
- Division of Gastroenterology and Hepatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Paul Fitzmorris
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar I. Massoud
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Romano J, Sims OT, Richman J, Guo Y, Matin T, Shoreibah M, Kommineni V, Venkata K, Massoud OI. Resolution of ascites and hepatic encephalopathy and absence of variceal bleeding in decompensated hepatitis C virus cirrhosis patients. JGH Open 2018; 2:317-321. [PMID: 30619944 PMCID: PMC6308043 DOI: 10.1002/jgh3.12091] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 06/17/2018] [Accepted: 08/20/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The aims of this study were to examine changes in the proportion of decompensated hepatitis C virus (HCV) cirrhosis patients with ascites, hepatic encephalopathy, and variceal bleeding at pretreatment compared to 3 and 12 months post-sustained virological response (SVR) and to compare pretreatment and post-SVR model of end-stage liver disease and Child-Pugh scores and alpha-fetoprotein levels. METHODS Electronic medical records of 64 decompensated HCV cirrhosis patients who received direct-acting antivirals were reviewed. The McNemar-Bowker test and the Wilcoxon-Signed Rank test were used to compare patient outcomes. RESULTS Ascites was resolved in 29% of patients 3 months post-SVR (65% vs 36%, P < 0.01) and in 35% of patients 12 months post-SVR (65% vs 30%, P = 0.07). Hepatic encephalopathy was resolved in 54% of patients 3 months post-SVR (70% vs 16%, P < 0.01) and in 48% of patients 12 months post-SVR (70% vs 22% P = 0.03). Variceal bleeding was absent in 32% of patients 3 months post-SVR (35% vs 3%, P < 0.01) and in 27% of patients 12 months post-SVR (35% vs 8%, P < 0.01). Alpha-fetoprotein levels were significantly reduced post-SVR, but model of end-stage liver disease and Child-Pugh scores were not. CONCLUSIONS Decompensated HCV cirrhosis patients who achieved SVR with direct-acting antiviral treatment had significant reductions in manifestations of hepatic decompensation sustainable up to 1 year post-SVR.
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Affiliation(s)
- John Romano
- Department of Internal Medicine, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Omar T. Sims
- Department of Social Work, College of Arts and SciencesUniversity of Alabama at BirminghamBirminghamAlabamaUSA
- Department of Health Behavior, School of Public HealthUniversity of Alabama at BirminghamBirminghamAlabamaUSA
- Center for AIDS Research, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
- Comprehensive Center for Healthy Aging, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Joshua Richman
- Department of Surgery, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Yuqi Guo
- School of Social WorkUniversity of AlabamaTuscaloosaAlabamaUSA
| | - Tasnia Matin
- University of Alabama at BirminghamBirminghamAlabamaUSA
| | - Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, School of Medicine, Birmingham Veterans Affairs HospitalUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Vishnu Kommineni
- Department of Internal Medicine, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Krishna Venkata
- Department of Internal Medicine, School of MedicineUniversity of Alabama at BirminghamBirminghamAlabamaUSA
| | - Omar I. Massoud
- Division of Gastroenterology & Hepatology, School of Medicine, Birmingham Veterans Affairs HospitalUniversity of Alabama at BirminghamBirminghamAlabamaUSA
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2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C. Clin Mol Hepatol 2018; 24:169-229. [PMID: 30092624 PMCID: PMC6166104 DOI: 10.3350/cmh.2018.1004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 03/06/2018] [Indexed: 12/11/2022] Open
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Grottenthaler JM, Werner CR, Steurer M, Spengler U, Berg T, Engelmann C, Wedemeyer H, von Hahn T, Stremmel W, Pathil A, Seybold U, Schott E, Blessin U, Sarrazin C, Welker MW, Harrer E, Scholten S, Hinterleitner C, Lauer UM, Malek NP, Berg CP. Successful direct acting antiviral (DAA) treatment of HCV/HIV-coinfected patients before and after liver transplantation. PLoS One 2018; 13:e0197544. [PMID: 29874250 PMCID: PMC5991346 DOI: 10.1371/journal.pone.0197544] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 05/03/2018] [Indexed: 12/15/2022] Open
Abstract
Objectives The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively. Methods When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)). Results Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up. Conclusion DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.
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Affiliation(s)
- Julia M. Grottenthaler
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tuebingen, Tuebingen, Germany
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
| | - Christoph R. Werner
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tuebingen, Tuebingen, Germany
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
| | - Martina Steurer
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tuebingen, Tuebingen, Germany
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
| | - Ulrich Spengler
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Thomas Berg
- Division of Gastroenterology and Hepatology, University Hospital Leipzig, Leipzig, Germany
| | - Cornelius Engelmann
- Division of Gastroenterology and Hepatology, University Hospital Leipzig, Leipzig, Germany
| | - Heiner Wedemeyer
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
| | - Thomas von Hahn
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
| | - Wolfgang Stremmel
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Anita Pathil
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Ulrich Seybold
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Division of Infectious Diseases, Medizinische Poliklinik-Innenstadt, University of Munich, Munich, Germany
| | - Eckart Schott
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Usha Blessin
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christoph Sarrazin
- Department of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany
| | - Martin-Walter Welker
- Department of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany
| | - Ellen Harrer
- Department of Internal Medicine 3, Institute of Clinical Immunology, University Hospital Erlangen, Erlangen, Germany
| | | | - Clemens Hinterleitner
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Medical Oncology, Haematology, Immunology, Rheumatology and Pulmology, University Hospital Tuebingen, Tuebingen, Germany
| | - Ulrich M. Lauer
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- Department of Clinical Tumor Biology, University Hospital Tuebingen, Tuebingen, Germany
| | - Nisar P. Malek
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tuebingen, Tuebingen, Germany
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
| | - Christoph P. Berg
- Department of Gastroenterology, Hepatology, and Infectiology, University Hospital Tuebingen, Tuebingen, Germany
- German Center for Infection Research (DZIF) partner site, Tuebingen, Bonn, Hannover, Heidelberg, Munich, Germany
- * E-mail:
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Kawano A, Shigematsu H, Miki K, Ichiki Y, Morita C, Yanagita K, Takahashi K, Dohmen K, Nomura H, Ishibashi H, Shimoda S. Diabetes Mellitus Prevents an Improvement in the Serum Albumin Level During Interferon-free Sofosbuvir-based Therapy for Chronic Hepatitis C Patients: A Multi-institutional Joint Study. Intern Med 2018; 57:1533-1542. [PMID: 29321441 PMCID: PMC6028685 DOI: 10.2169/internalmedicine.9857-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 09/28/2017] [Indexed: 11/06/2022] Open
Abstract
Objective Interferon-free regimens of direct-acting antiviral agents have improved the treatment response for chronic hepatitis C virus (HCV) infection, and improvement in the serum albumin level during interferon-free therapy has been reported. The aim of this study was to identify the factors that influence the improvement in the serum albumin level in patients receiving interferon-free antiviral therapy. Methods This retrospective, multicenter study consisted of 471 Japanese patients with chronic hepatitis and compensated liver cirrhosis infected with HCV who completed 12-week interferon-free sofosbuvir (SOF)-based therapy [SOF plus ledipasvir for genotype 1 (n=276) and SOF with ribavirin for genotype 2 (n=195)]. We evaluated the changes in the serum albumin level from baseline to the end of treatment (ΔAlb). Results When compared with the normal-albumin group (baseline serum albumin >35 g/L, n=406), the low-albumin group (baseline serum albumin ≤35 g/L, n=65) showed a significant increase in the mean ΔAlb (5.5 g/L vs. 1.0 g/L, p<0.001). In the low-albumin group, a multivariate logistic regression analysis extracted diabetes mellitus as a negative predictive factor of median ΔAlb >5.0 g/L (odds ratio: 0.19, 95% confidence interval: 0.048-0.79, p=0.020). In the low-albumin group, the mean ΔAlb was significantly lower in the diabetic patients (n=14) than in the non-diabetic patients (n=51) (3.9 g/L and 5.7 g/L, p=0.049). Conclusion Interferon-free SOF-based therapy significantly improved the serum albumin in the low-albumin group patients with chronic HCV infection. However, the improvement in the serum albumin level was significantly lower in the diabetic patients than in the non-diabetic patients.
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Affiliation(s)
- Akira Kawano
- Department of Internal Medicine, Kitakyushu Municipal Medical Center, Japan
| | | | - Koichiro Miki
- Department of Internal Medicine, Kitakyushu Municipal Medical Center, Japan
| | - Yasunori Ichiki
- Department of Internal Medicine, Japan Community Health care Organization Kyushu Hospital, Japan
| | - Chie Morita
- Department of Internal Medicine, JR Kyushu Hospital, Japan
| | | | | | | | | | - Hiromi Ishibashi
- Department of Hepato-Biliary-Pancreatic Medicine, Fukuoka Sanno Hospital, Japan
| | - Shinji Shimoda
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Japan
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Daniel KE, Said A. Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate. Curr Gastroenterol Rep 2018; 20:20. [PMID: 29623506 DOI: 10.1007/s11894-018-0626-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies. RECENT FINDINGS Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association. Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.
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Affiliation(s)
- Kimberly E Daniel
- Gastroenterology and Hepatology Fellow, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Adnan Said
- Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health and Madison VAMC, Madison, WI, USA.
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HCV Therapy in Decompensated Cirrhosis before or after Liver Transplantation: A Paradoxical Quandary. Am J Gastroenterol 2018; 113:449-452. [PMID: 29206818 DOI: 10.1038/ajg.2017.435] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Kwo P, Fried MW, Reddy KR, Soldevila-Pico C, Khemichian S, Darling J, Zamor PJ, Napoli AA, Anduze-Faris B, Brown RS. Daclatasvir and sofosbuvir treatment of decompensated liver disease or post-liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real-world cohort. Hepatol Commun 2018; 2:354-363. [PMID: 29619415 PMCID: PMC5880197 DOI: 10.1002/hep4.1156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/08/2017] [Accepted: 01/11/2018] [Indexed: 12/12/2022] Open
Abstract
We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. (Hepatology Communications 2018;2:354‐363)
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Affiliation(s)
- Paul Kwo
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Palo Alto CA
| | - Michael W Fried
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology University of Pennsylvania Philadelphia PA
| | | | - Saro Khemichian
- Department of Medicine, Keck School of Medicine University of Southern California Los Angeles CA
| | - Jama Darling
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | | | | | | | - Robert S Brown
- Department of Medicine Weill Cornell Medicine New York NY
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Gadiparthi C, Cholankeril G, Perumpail BJ, Yoo ER, Satapathy SK, Nair S, Ahmed A. Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates. World J Gastroenterol 2018; 24:315-322. [PMID: 29391754 PMCID: PMC5776393 DOI: 10.3748/wjg.v24.i3.315] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 12/05/2017] [Accepted: 12/12/2017] [Indexed: 02/06/2023] Open
Abstract
Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.
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Affiliation(s)
- Chiranjeevi Gadiparthi
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States
| | - Brandon J Perumpail
- Drexel University College of Medicine, Philadelphia, PA 19129, United States
| | - Eric R Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, United States
| | - Sanjaya K Satapathy
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Satheesh Nair
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States
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Cholankeril G, Joseph-Talreja M, Perumpail BJ, Liu A, Yoo ER, Ahmed A, Goel A. Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era of Direct-acting Antiviral Agents. J Clin Transl Hepatol 2017; 5:363-367. [PMID: 29226102 PMCID: PMC5719193 DOI: 10.14218/jcth.2017.00007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 07/30/2017] [Accepted: 08/18/2017] [Indexed: 12/16/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) in the United States. While most patients with chronic HCV infection remain asymptomatic, up to one-third develop progressive liver disease resulting in cirrhosis. LT is often the only curative treatment once significant hepatic decompensation develops. However, antiviral therapy for HCV infection has advanced markedly in the past 5 years with the discovery and approval of direct-acting antiviral agents. These new regimens are well tolerated, of short duration and highly effective, unlike the traditional treatment with pegylated-interferon and ribavirin. As achieving sustained virological response becomes increasingly attainable for a majority of HCV-infected patients, concerns have been raised regarding the optimal timing of treatment for HCV infection in the setting of end-stage liver disease and during the peri-transplant period. On one hand, HCV treatment may improve hepatic function and negate the need for LT in some, which is crucial given the scarcity of donor organs and mortality on the waiting list in certain regions. On the other hand, HCV treatment may result in lowering the priority for LT without improving quality of life, thereby delaying potentially curative LT surgery. This review evaluates the evidence supporting the use of direct-acting antiviral agents in the period before and following LT.
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Affiliation(s)
- George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Mairin Joseph-Talreja
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Brandon J. Perumpail
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Andy Liu
- Department of Medicine, California Pacific Medical Center, San Francisco, CA, USA
| | - Eric R. Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
- *Correspondence to: Aijaz Ahmed, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite #210, Stanford, CA 94304, USA. Tel: +1-650-498-6091, Fax: +1-650-498-5692, E-mail:
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Pascasio JM, Vinaixa C, Ferrer MT, Colmenero J, Rubin A, Castells L, Manzano ML, Lorente S, Testillano M, Xiol X, Molina E, González-Diéguez L, Otón E, Pascual S, Santos B, Herrero JI, Salcedo M, Montero JL, Sánchez-Antolín G, Narváez I, Nogueras F, Giráldez Á, Prieto M, Forns X, Londoño MC. Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation. J Hepatol 2017; 67:1168-1176. [PMID: 28842296 DOI: 10.1016/j.jhep.2017.08.008] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 08/09/2017] [Accepted: 08/09/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.
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Affiliation(s)
- Juan Manuel Pascasio
- UGC Digestive Diseases, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, Spain
| | - Carmen Vinaixa
- Liver Unit, Digestive Medicine Service, Hospital Universitario La Fé, CIBERehd, Valencia, Spain
| | - María Teresa Ferrer
- UGC Digestive Diseases, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, Spain
| | - Jordi Colmenero
- Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Angel Rubin
- Liver Unit, Digestive Medicine Service, Hospital Universitario La Fé, CIBERehd, Valencia, Spain
| | - Lluis Castells
- Internal Medicine Service, Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
| | - María Luisa Manzano
- Digestive Diseases Service, Hospital Universitario 12 Octubre, Madrid, Spain
| | - Sara Lorente
- Liver Transplant Unit, Digestive Diseases Service, Hospital Universitario Lozano Blesa, Zaragoza, Spain
| | - Milagros Testillano
- Liver Unit, Digestive Diseases Service, Hospital Universitario Cruces, Vizcaya, Spain
| | - Xavier Xiol
- Digestive Diseases Service, Hospital Universitari Bellvitge, Barcelona, Spain
| | - Esther Molina
- Abdominal Transplant Unit, CHU Santiago de Compostela, IDIS, Santiago, Spain
| | | | - Elena Otón
- Digestive Diseases Service, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
| | - Sonia Pascual
- Liver Unit, Hospital General Universitario, CIBERehd, Alicante, Spain
| | - Begoña Santos
- Internal Medicine Service, Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
| | | | - Magdalena Salcedo
- Liver Transplant Unit, Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid, Spain
| | - José Luis Montero
- UGC Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, Spain
| | | | - Isidoro Narváez
- Digestive Diseases Service, Hospital Universitario Infanta Cristina, Badajoz, Spain
| | - Flor Nogueras
- Digestive Diseases Service, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Álvaro Giráldez
- UGC Digestive Diseases, Hospital Universitario Virgen del Rocío, IBIS, CIBERehd, Sevilla, Spain
| | - Martín Prieto
- Liver Unit, Digestive Medicine Service, Hospital Universitario La Fé, CIBERehd, Valencia, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain
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Verna EC. HCV treatment in patients with decompensated liver disease. Clin Liver Dis (Hoboken) 2017; 10:83-86. [PMID: 31186892 PMCID: PMC6499224 DOI: 10.1002/cld.663] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Revised: 08/07/2017] [Accepted: 08/09/2017] [Indexed: 02/04/2023] Open
Affiliation(s)
- Elizabeth C. Verna
- Center for Liver Disease and TransplantationColumbia University Medical CenterNew YorkNY
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HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency. Transplantation 2017; 101:924-932. [PMID: 28212220 DOI: 10.1097/tp.0000000000001688] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective direct-acting antiviral therapy, such that most patients can be cured in the pretransplant or posttransplant setting. In addition, there are now direct-acting antiviral regimens specifically approved for use in patients with severe renal insufficiency. However, patients with pre or posttransplant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism in hepatic and renal failure, as well as posttransplant drug-drug interactions. Treatment options are even more restricted in non-1 HCV genotypes. Because renal insufficiency is common among patients with HCV, with decompensated cirrhosis, and in the posttransplant setting, this difficult scenario is relatively common. However, ongoing development of pangenotypic regimens with improved safety profiles, as well as additional data on dosing and safety among patients with severe renal insufficiency, will continue to expand options for cure even in these most difficult to treat patients.
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Fernández Carrillo C, Crespo G, de la Revilla J, Castells L, Buti M, Montero JL, Fábrega E, Fernández I, Serrano-Millán C, Hernández V, Calleja JL, Londoño MC. Successful Continuation of HCV Treatment After Liver Transplantation. Transplantation 2017; 101:1009-1012. [PMID: 27906834 DOI: 10.1097/tp.0000000000001596] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus before surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is 1 potential solution which has not been investigated widely. METHODS Patients from 5 clinical centers included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents while awaiting LT were identified retrospectively and followed up prospectively. Fifteen patients who had treatment interruptions around LT were identified. RESULTS The majority of patients (12/15) received interferon-free regimens, most commonly sofosbuvir + daclatasvir (8/12), for a total of 24 weeks (13/15). Treatment was discontinued temporarily for a median of 5 (range, 2-33) days. Fourteen patients completing 12 weeks of follow-up achieved a sustained virological response. One patient who died before week 12 posttreatment achieved a response at posttreatment week 4. Treatment was generally well tolerated. Serious adverse events were recorded in 2 of 15 patients (anaemia in 1 patient; pneumonia in 1 patient); all arose after LT. CONCLUSIONS Resumption of direct-acting antiviral agent therapy after a temporary interruption around LT was highly effective, achieving sustained virological response in all patients who completed 12 weeks of posttreatment follow-up. Treatment was generally well tolerated pretransplantation and posttransplantation, with a low rate of serious adverse events. Such a strategy may offer an important new approach to the treatment of patients awaiting LT which may be assessed in future studies.
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Affiliation(s)
- Carlos Fernández Carrillo
- 1 Liver Unit, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHIM, CIBERehd, Majadahonda, Madrid, Spain. 2 Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. 3 Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, CIBERehd, Barcelona, Spain. 4 Hepatology and Liver Transplant Unit, Hospital Universitario Reina Sofía, IMIBIC, CIBERehd, Córdoba, Spain. 5 Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. 6 Digestive Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 7 Liver Unit, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid and CIBERehd, Madrid, Spain
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Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review. Transplantation 2017; 101:916-923. [PMID: 28060241 DOI: 10.1097/tp.0000000000001633] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered "difficult to treat and cure patients," additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic "recompensation," reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.
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Factors associated with contralateral liver hypertrophy after unilateral radioembolization for hepatocellular carcinoma. PLoS One 2017; 12:e0181488. [PMID: 28708902 PMCID: PMC5510860 DOI: 10.1371/journal.pone.0181488] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 06/30/2017] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION Radioembolization for the treatment of hepatocellular carcinoma (HCC) induces liver volume changes referred to as "atrophy-hypertrophy complex". The aim of this study was to investigate lobar liver volume changes after unilateral radioembolization and to search for factors associated with hypertrophy of the untreated lobe. MATERIALS AND METHODS Seventy-five patients were retrospectively evaluated. Inclusion criteria were: (1) right-lobar radioembolization for unresectable unilateral HCC, (2) available liver computed tomography scans before, 1, 3, and at least 6 months after radioembolization. Baseline patient characteristics included clinical features, laboratory results, spleen volume, and liver computed tomography. Absolute and relative (referred to the whole liver volume) liver lobe volumes (LLV) as well as relative LLV (rLLV) change per month were evaluated and compared. RESULTS Absolute and relative contralateral LLV continuously increased after radioembolization (p<0.001). Mean relative contralateral LLV increased from 36±11.6% before radioembolization to 50±15.3% 6 months after radioembolization. Median contralateral rLLV increase/month (within first 6 months) was 2.5%. Contralateral rLLV increase/month was significantly lower in patients with ascites (p = 0.017) or platelet count <100/nl (p = 0.009). An inverse correlation of contralateral rLVV increase/month with spleen volume (p = 0.017), patient age (p = 0.024), Child Pugh score (p = 0.001), and tumor burden (p = 0.001) was found. CONCLUSIONS Significant contralateral hypertrophy and ipsilateral atrophy were common after unilateral radioembolization. Small spleen volume, low patient age, low Child Pugh score, absence of ascites, platelet count ≥100/nl, and low tumor burden were associated with increased contralateral hypertrophy, indicating that younger patients with compensated cirrhosis might benefit most from radioembolization in a "bridge-to-resection" setting.
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Jeffrey AW, Huang Y, de Boer WB, Adams LA, MacQuillan G, Speers D, Joseph J, Jeffrey GP. Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome. World J Hepatol 2017; 9:850-856. [PMID: 28740596 PMCID: PMC5504360 DOI: 10.4254/wjh.v9.i19.850] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 04/30/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish if serial Hepascore tests (referred to as delta Hepascore) in those with chronic hepatitis C (CHC) correlate with the increase and/or decrease in risk of liver related complications.
METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28 (8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis and subsequent clinical outcomes in chronic liver disease.
RESULTS Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation (P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint (P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year (P = 0.03).
CONCLUSION In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.
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Ahmed A, Gonzalez SA, Cholankeril G, Perumpail RB, McGinnis J, Saab S, Beckerman R, Younossi ZM. Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States. Hepatology 2017; 66:46-56. [PMID: 28257591 DOI: 10.1002/hep.29137] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Revised: 01/13/2017] [Accepted: 02/24/2017] [Indexed: 12/15/2022]
Abstract
UNLABELLED All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).
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Affiliation(s)
- Aijaz Ahmed
- Stanford University School of Medicine, Stanford, CA
| | | | | | | | | | - Sammy Saab
- University of California Los Angeles, Los Angeles, CA
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Martini S, Tandoi F, Terzi di Bergamo L, Strona S, Lavezzo B, Sacco M, Maione F, Gonella F, Strignano P, Dell Olio D, Salizzoni M, Saracco GM, Romagnoli R. Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C-positive recipients. Liver Transpl 2017; 23:915-924. [PMID: 28422425 DOI: 10.1002/lt.24772] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 03/15/2017] [Accepted: 04/07/2017] [Indexed: 12/13/2022]
Abstract
Although early allograft dysfunction (EAD) negatively impacts survival from the first months following liver transplantation (LT), direct-acting antiviral agents (DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the EAD definition best predicting 90-day graft loss and identified EAD risk factors in HCV-positive recipients. From November 2002 to June 2016, 603 HCV-positive patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV-negative donors. The median recipient Model for End-Stage Liver Disease (MELD) score was 15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre-LT antiviral therapy (61 patients) or pre-LT plus a pre-emptive post-LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3 different EAD definitions: (1) bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on day 7 after LT or aspartate aminotransferase or alanine aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on days 2-7 after LT; and (3) MELD ≥ 19 on day 5 after LT. EAD defined by MELD ≥ 19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90-day graft loss. At 90 days after LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P < 0.001). At multivariate analysis, considering variables available at LT, MELD at LT of >25 (OR = 7.4) or 15-25 (OR = 3.2), graft macrovesicular steatosis ≥ 30% (OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0), earlier LT era (OR = 1.8), and cold ischemia time ≥ 8 hours (OR = 1.8) were significant risk factors for EAD. In conclusion, in HCV-positive patients, MELD ≥ 19 on day 5 after LT best predicts 90-day graft loss. Preventing graft infection by pre-/peri-LT antiviral therapy reduces EAD incidence and could be most beneficial in high-MELD patients and recipients of suboptimal grafts. Liver Transplantation 23 915-924 2017 AASLD.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Dominic Dell Olio
- Regional Transplant Center, Piedmont, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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Yu ML, Chen YL, Huang CF, Lin KH, Yeh ML, Huang CI, Hsieh MH, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL. Paritaprevir/ritonavir/ombitasvir plus dasabuvir with ribavirin for treatment of recurrent chronic hepatitis C genotype 1 infection after liver transplantation: Real-world experience. J Formos Med Assoc 2017; 117:518-526. [PMID: 28662883 DOI: 10.1016/j.jfma.2017.06.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 05/17/2017] [Accepted: 06/12/2017] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/AIMS The registered trial has demonstrated that paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) with ribavirin was effective for recurrent hepatitis C virus genotype 1 (HCV-1) infection after liver transplantation in patients with mild fibrosis; however, the real-world efficacy and safety of this regimen have not been determined. METHODS The efficacy (sustained virological response, SVR12, undetectable HCV RNA 12 weeks post-treatment) and safety were evaluated in 12 patients with recurrent HCV-1 infection after liver transplantation. RESULTS Nine patients were treated for 24 weeks, and three patients (two treatment-naïve patients and one interferon-intolerant patient) were treated for 12 weeks. HCV RNA was undetectable at treatment day 1, week 1, week 4, week 12, and at the end of treatment in 8.3% (n = 1), 25% (n = 3), 83.3% (n = 10), 100% (n = 12), and 100% (n = 12) of patients, respectively. All twelve patients achieved SVR12. Treatment was temporarily stopped in one patient because of leucopenia. The other patient with minimal fibrosis experienced an elevation in alanine aminotransferase concentration, which returned to normal levels after dose reduction. Seven (58.3%) patients required RBV dose reduction and two (16.7%) required transient RBV discontinuation during treatment. There were no serious adverse events, and most adverse events were related to ribavirin. No patient developed graft rejection or deterioration in hepatic or renal function during treatment. Treatment efficacy and safety were comparable between patients with and without advanced liver fibrosis. CONCLUSION PrOD plus ribavirin had a highly satisfactory real-world efficacy and safety profile in the treatment of recurrent HCV-1 infection after liver transplantation in Asian patients.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Taiwan; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Yao-Li Chen
- Transplantation Center, Third Xiangya Hospital of Central South University, Changsha, China; Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Hua Lin
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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