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1
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Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D, Wang H. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med 2025; 57:2455539. [PMID: 39834076 PMCID: PMC11753015 DOI: 10.1080/07853890.2025.2455539] [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: 10/21/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength. METHODS This umbrella review of meta-analyses was conducted throughout PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. Evidence strength was evaluated according to the evidence categories criteria. RESULTS We identified 101 risk factors throughout 175 meta-analyses. 31 risk factors were classified as evidence levels of class I, II, or III. HBV and HCV infections increase HCC risk by 12.5-fold and 11.2-fold, respectively. These risks are moderated by antiviral treatments and virological responses but are exacerbated by higher HBsAg levels, anti-HBc positivity, and co-infection. Smoking, obesity, non-alcoholic fatty liver disease, diabetes, low platelet, elevated liver enzymes and liver fluke infection increase HCC risk, while coffee consumption, a healthy diet, and bariatric surgery lower it. Medications like metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), aspirin, statins, and selective serotonin reuptake inhibitors reduce HCC risk, while acid suppressive agents, particularly proton pump inhibitors, elevate it. Blood type O reduces the risk of HCC, while male gender and older age increase the risk. CONCLUSIONS HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.
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Affiliation(s)
- Jie Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Kaijie Qiu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Songsheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Yichao Gan
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Keting Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Donghuan Wang
- Operations Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Haibiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
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2
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Yasuura N, Suda G, Ohara M, Meno A, Sho T, Kohya R, Sasaki T, Yoda T, Yoshida S, Fu Q, Yang Z, Hosoda S, Maehara O, Ohnishi S, Saitou T, Sugiyama M, Fukuhara T, Baba M, Kitagataya T, Kawagishi N, Nakai M, Natsuizaka M, Ogawa K, Taketomi A, Sakamoto N. Positivity of high-sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non-HBV-related HCC. Aliment Pharmacol Ther 2024; 60:1315-1324. [PMID: 39228289 DOI: 10.1111/apt.18229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 06/26/2024] [Accepted: 08/15/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND AND AIMS The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. METHODS We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC. RESULTS A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC. CONCLUSIONS In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.
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Grants
- JP24fk0210126,JP24fk0310501,JP24fk0210121,JP24fk0210112,JP24fk0210142,JP24fk0210111,JP24fk0310524,JP24fk0210123,JP24fk0210157,JP24fk0310518,JP24fk0210103,JP24fk0210104,JP24fk0210113,andJP24fk0210143 Japan Agency for Medical Research and Development
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Affiliation(s)
- Naohiro Yasuura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Akimitsu Meno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Risako Kohya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Takashi Sasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Tomoka Yoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Sonoe Yoshida
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Qingjie Fu
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Zijian Yang
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Shunichi Hosoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Osamu Maehara
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Shunsuke Ohnishi
- Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
| | - Tomoya Saitou
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masaya Sugiyama
- Department of Viral Pathogenesis and Controls, National Center for Global Health Medicine, Tokyo, Japan
| | - Takasuke Fukuhara
- Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Masaru Baba
- Center for Gastroenterology and Hepatology, Japan Community Healthcare Organization Hokkaido Hospital, Sapporo, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Morozov S, Batskikh S. Reactivation of hepatitis B virus infection - an important aspect of multifaceted problem. World J Gastroenterol 2024; 30:3193-3197. [PMID: 39086636 PMCID: PMC11287409 DOI: 10.3748/wjg.v30.i26.3193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 07/09/2024] Open
Abstract
In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the problem of occult hepatitis B virus (HBV) infection, that is a result of previous hepatitis B (PHB) and a source for reactivation of HBV. The prevalence of PHB is underestimated due to the lack of population testing programs. However, this condition not only complicate anticancer treatment, but may be responsible for the development of other diseases, like cancer or autoimmune disorders. Here we unveil possible mechanisms responsible for realization of these processes and suggest practical approaches for diagnosis and treatment.
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Affiliation(s)
- Sergey Morozov
- Department of Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow 115446, Russia
| | - Sergey Batskikh
- Department of Hepatology, Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia
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4
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Yano Y, Sato I, Imanishi T, Yoshida R, Matsuura T, Ueda Y, Kodama Y. Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen. Diagnostics (Basel) 2024; 14:728. [PMID: 38611641 PMCID: PMC11011781 DOI: 10.3390/diagnostics14070728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.
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Affiliation(s)
- Yoshihiko Yano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Itsuko Sato
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Takamitsu Imanishi
- Department of Clinical Laboratory, Kobe University Hospital, Kobe 650-0017, Japan; (I.S.); (T.I.)
| | - Ryutaro Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Takanori Matsuura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yoshihide Ueda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; (R.Y.); (T.M.); (Y.U.); (Y.K.)
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Freeland C, Sreepathi V, Hass RW, Fenkel JM, Torgersen J, Rothstein K, Cohen C, Gish RG. The importance of triple panel testing for hepatitis B and the burden of isolated anti-hepatitis B core antibodies within a community sample. J Virus Erad 2023; 9:100358. [PMID: 38174110 PMCID: PMC10761777 DOI: 10.1016/j.jve.2023.100358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 12/06/2023] [Indexed: 01/05/2024] Open
Abstract
Within the United States (US), 2.4 million individuals are living with chronic hepatitis B, but less than 20% are diagnosed. Isolated anti-hepatitis B core (iAHBc) antibodies indicate serology in an individual that is positive for anti-HBc antibodies, while negative for surface antigen (HBsAg) and surface antibodies (anti-HBs). A result of iAHBc could indicate a chronic occult bloodstream infection, necessitating further testing. This study assesses the prevalence and risk factors associated with anti-HBc and iAHBc within community high-risk screening in Greater Philadelphia. Participants (n = 177) were screened for HBsAg, anti-HBs, and anti-HBc during community screening events in 2022. Chi-square tables and Firth logistic regression were used to describe the data and to assess the odds of iAHBc. The findings indicate that there was an iAHBc prevalence of 7.3% (n = 13) within our study. The odds of anti-HBc were increased for immigrants from the Western Pacific (4.5%) and Africa (11.9%). Individuals born in Africa had 7.93 greater odds for iAHBc than those born in the Americas, and these odds are multiplied by 1.01 for every 1-year increase in age. Our data show a high burden of iAHBc within high-risk and often hard-to-reach communities. Triple panel screening should be incorporated into all HBV screening programs, in accordance with current Centers for Disease Control and Prevention (CDC) universal screening recommendations, to ensure a comprehensive picture of the disease burden and reduce the risk of missing people with occult hepatitis B and those at risk for viral reactivation or liver complications.
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Affiliation(s)
| | - Vivek Sreepathi
- Thomas Jefferson University, College of Population Health Science, Philadelphia, PA, USA
| | - Richard W. Hass
- Thomas Jefferson University, College of Population Health Science, Philadelphia, PA, USA
| | - Jonathan M. Fenkel
- Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, PA, USA
| | - Jessie Torgersen
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Kenneth Rothstein
- University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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Surrogate Markers for Hepatitis B Virus Covalently Closed Circular DNA. Semin Liver Dis 2022; 42:327-340. [PMID: 35445388 DOI: 10.1055/a-1830-2741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Chronic infection with the hepatitis B virus (HBV) is one of the most common causes of liver disease worldwide. Chronic HBV infection is currently incurable because of the persistence of the viral template for the viral transcripts, covalently closed circular deoxyribonucleic acid (cccDNA). Detecting changes in cccDNA transcriptional activity is key to understanding fundamental virology, determining the efficacy of new therapies, and deciding the optimal clinical management of HBV patients. In this review, we summarize surrogate circulating biomarkers that have been used to infer cccDNA levels and activity in people with chronic hepatitis B. Moreover, we outline the current shortcomings of the current biomarkers and highlight the clinical importance in improving them and expanding their use.
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Hsieh YC, Pan MH, Jeng WJ, Hu HH, Liu J, Mizokami M, Chen CJ, Yang HI. Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV. Clin Gastroenterol Hepatol 2022; 21:1303-1313.e11. [PMID: 35850414 DOI: 10.1016/j.cgh.2022.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 06/15/2022] [Accepted: 06/21/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatitis B core-related antigen (HBcrAg) is a surrogate seromarker of intrahepatic hepatitis B virus covalently closed circular DNA quantity and activity and a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B patients. We assess association between HBcrAg and HCC in individuals seronegative for hepatitis B surface antigen and anti-hepatitis C virus (NBNC) in Taiwan. METHODS A total of 129 newly developed HCC cases and 520 frequency-matched non-HCC controls were drawn from the REVEAL-NBNC cohort. Serum HBcrAg and other risk factors measured at recruitment were compared between cases and controls. Regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS The proportion of baseline HBcrAg positivity (≥1000 U/mL) was significantly higher in HCC cases than in controls (12.4% vs 1.4%, P < .001). In multivariate analysis, HBcrAg positivity was associated with significantly higher risk of HCC (adjusted OR [95% CI]: 9.3 [3.3-26.4]; P < .001]. The HCC population attributable to HBcrAg positivity was 11.1% (95% CI: 9.7%-12.5%). CONCLUSIONS Seropositivity of HBcrAg might identify a subset of the NBNC population at higher risk of HCC in hepatitis B virus endemic areas.
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Affiliation(s)
- Yi-Chung Hsieh
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan; Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; College of Medicine, Chang Gung University, Taiwan
| | - Mei-Hung Pan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan; Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Hui-Han Hu
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jessica Liu
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Perinatal Epidemiology and Health Outcomes Research Unit, Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California; California Perinatal Quality Care Collaborative, Palo Alto, California
| | - Masashi Mizokami
- Genome Medical Science, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan.
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8
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Sono S, Sae-Chan J, Kaewdech A, Chamroonkul N, Sripongpun P. HBV seroprevalence and liver fibrosis status among population born before national immunization in Southern Thailand: Findings from a health check-up program. PLoS One 2022; 17:e0270458. [PMID: 35749545 PMCID: PMC9231792 DOI: 10.1371/journal.pone.0270458] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/12/2022] [Indexed: 11/18/2022] Open
Abstract
Background Hepatitis B virus (HBV) infection is the leading cause of liver-related death worldwide, particularly in Asia. Patients with either current or past HBV infection are at risk of cirrhosis and hepatocellular carcinoma (HCC). Here, we investigated the HBV seroprevalence in residents of southern Thailand born before the national vaccination program. Methods A cross-sectional study of individuals born before the nationwide HBV vaccination program who sought check-up programs which included HBV serology and abdominal ultrasound at a tertiary care hospital in southern Thailand from 2019 to 2020 was conducted. HBV serology, cirrhosis and liver fibrosis status (determined by ultrasonography and FIB-4), and clinical notes regarding management following HBsAg+ detection were obtained. Results Of 1,690 eligible individuals, the overall prevalence of HBsAg+ and HBsAg-antiHBc+, indicating current and past HBV infections, were 2.9% and 27.8%, respectively. Among current HBV patients, 87.8% were unaware of their infection. Cirrhosis was found in 8.2%, 1.1%, and 0.3% of patients with current, past, and no HBV infection, respectively (p<0.001). One-fourth of past HBV patients had FIB-4≥1.45, which indicated indeterminate or significant liver fibrosis, which may increase the risk of HCC. Conclusion The prevalence of HBsAg+ in Southern Thailand was 2.9%, and that of past infection (HBsAg-antiHBc+) was 27.8%. Patients with current and past HBV infection have an increased risk of cirrhosis and significant liver fibrosis. Most current HBV patients were unaware of their infection. Identifying patients with current and past HBV infection who are at risk for HCC and linking them to a cascade of care is necessary to reduce the burden of HBV-related liver diseases in Thailand.
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Affiliation(s)
- Supinya Sono
- Division of Family and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- Srivejchavat Premium Center, Songklanagarind Hospital, Hat Yai, Thailand
| | - Jirayu Sae-Chan
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Apichat Kaewdech
- Srivejchavat Premium Center, Songklanagarind Hospital, Hat Yai, Thailand
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- * E-mail: (PS); (NC)
| | - Pimsiri Sripongpun
- Srivejchavat Premium Center, Songklanagarind Hospital, Hat Yai, Thailand
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- * E-mail: (PS); (NC)
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Çakal B, Çavuş B, Atasoy A, Poda M, Bulakçi M, Güllüoğlu M, Demirci M, Şener LT, Altunok D, Arslan AB, Akyüz F. What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C? Microbiol Immunol 2022; 66:386-393. [PMID: 35661243 DOI: 10.1111/1348-0421.13012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/20/2022] [Accepted: 06/01/2022] [Indexed: 11/29/2022]
Abstract
Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (p<0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (p<0.05). Positive anti-HBc results may predict OBI and also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Bülent Çakal
- Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Bilger Çavuş
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Alp Atasoy
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehveş Poda
- Department of Genetics, Aziz Sancar Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
| | - Mesut Bulakçi
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mehmet Demirci
- Department of Medical Microbiology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Leyla Türker Şener
- Department of Biophysics Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Damla Altunok
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Filiz Akyüz
- Division of Gastroenterohepatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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10
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Xia R, Peng J, He J, Jiang P, Yuan C, Liu X, Yao Y. The Serious Challenge of Occult Hepatitis B Virus Infection-Related Hepatocellular Carcinoma in China. Front Microbiol 2022; 13:840825. [PMID: 35197961 PMCID: PMC8859271 DOI: 10.3389/fmicb.2022.840825] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/12/2022] [Indexed: 12/16/2022] Open
Abstract
Background It is unknown how many people in China have chronic occult hepatitis B virus (HBV) infection (OBI) [chronic HBV infection with negative serum hepatitis B surface antigen (HBsAg) (N-HBsAg)]. Their clinical and virological characteristics, especially the correlation between the OBI and hepatocellular carcinoma (HCC), are still elusive and need to be investigated, including prevention, early diagnosis, and treatment strategies. Methods 138 patients with HCC related to OBI were screened from 698 patients of HCC associated with HBV infection, their characteristics of epidemiology, clinical, biochemistry, virology, diagnostics, and therapeutics were analyzed retrospectively. Furthermore, the correlation between virological features and clinical features was investigated. Results It was found that 19.8% (138/698) of patients with HBV-related HCC were OBI, of which 79.7% (110/138) were men, and 20.3% (28/138) were women. Most of the patients with OBI-related HCC were older men, and the median age was 63.2 years. In total 78.3% (108/138) of the patients had apparent right upper abdomen discomfort and/or pain and then sought medical examination, while 21.7% (30/138) of the patients were identified by health examination. A total of 10.9% (15/138) of the patients were admitted with chronic infection of HBV, and 2.2% (3/138) of the patients were admitted with a family history of hepatitis B. The alpha-fetoprotein (AFP) serum-positive rate was 39.1% (54/138). Tumor lesions >5.0 cm, with intrahepatic and/or extrahepatic metastasis, were found in 72.5% (100/138) of the patients. The diameter of the tumor in the Group of hepatitis B core antibody-positive [HBcAb(+)] and hepatitis B surface antibody-positive [HBsAb(+)] was 7.03 ± 3.76 cm, which was much smaller than 8.79 ± 4.96 cm in the Group of HBcAb(+) and HBsAb(−) (P = 0.035). Conclusion It is estimated that at least 21 million OBI patients live in China. HBcAb(+) was not only the evidence of chronic HBV infection but also a dangerous mark for surface antigen-negative patients. A semi-annual or annual medical checkup is essential for all OBI patients to identify HCC as early as possible. The hypothesis underlying our analysis was that hepatitis B surface antibody would prevent the progress of HCC and facilitate the clearance of HBV in patients with OBI. Thereby, the hepatitis B vaccine could be used to prevent severe disease consequences.
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Wu HC, Jeng WJ, Pan MH, Hsieh YC, Lu SN, Chen CJ, Yang HI. Incidence of hepatocellular carcinoma in a community-based Taiwanese population without chronic HBV/HCV infection. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2022; 4:100410. [PMID: 35079699 PMCID: PMC8777288 DOI: 10.1016/j.jhepr.2021.100410] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 09/27/2021] [Accepted: 11/12/2021] [Indexed: 02/07/2023]
Abstract
Background & Aims In addition to HBV/HCV causing hepatocellular carcinoma (HCC), other risk factors including obesity and alcohol drinking also increase risk. We describe the cumulative risk of HCC and mortality from liver-related disease by selected modifiable risk factors among a non-hepatitis virus-infected population. Methods For a community-based cohort, residents aged 30–65 years living in 7 townships in Taiwan were recruited, and have been followed up since 1991. A total of 18,541 individuals were seronegative for markers of chronic infection of HBV/HCV and with no history of HCC at baseline. New non-HBV/HCV HCC cases and liver-related deaths were ascertained through data linkage to the National Cancer Registry and Death Certification System from 1 January 1991 through 31 December 2017. Results There were 207 HCC cases and 215 liver-related deaths identified. The incidence rate of non-HBV/HCV HCC was 47.2 per 100,000 person-years. The mortality rate of liver-related death was 49.0 per 100,000 person-years. Baseline information on alcohol consumption, heart disease, diabetes, elevated aspartate aminotransferase, and alanine aminotransferase predicted higher risks of HCC, with hazard ratios (HRs) (95% CIs) of 1.7 (1.1–2.5), 2.2 (1.1–4.1), 1.9 (1.0–3.5), 1.7 (1.1–2.4), and 1.6 (1.0–2.4), respectively. The HRs (95% CIs) of liver-related death were 2.3 (1.6–3.2) for alcohol consumption, 1.4 (1.1–1.9) for BMI ≥25 kg/m2, 2.2 (1.4–3.3) for elevated aspartate aminotransferase, and 1.5 (1.0–2.4) for elevated alanine aminotransferase. The HR (95% CI) was 8.1 (3.6–18.5) for those with diabetes and elevated aspartate aminotransferase. Conclusions Individuals with elevated liver enzymes are at high risk of liver disease. Prevention and treatment of diabetes and heart disease are critical for non-hepatitis B, non-hepatitis C (NonB/C)-HCC. Lay summary We followed up individuals with no chronic HBV or HCV infection and described the risk of hepatocellular carcinoma (HCC, the most common form of primary liver cancer) and mortality from liver-related disease by modifiable risk factors. This study estimated the incidence rate of HCC by selected lifestyle risk factors and chronic diseases conditions. Alcohol consumption, heart disease, diabetes, and abnormal blood liver function tests showed a strong association with HCC risk and mortality.
Alcohol drinking increases risks of NonB/C-HCC and liver-related death. Both heart disease and diabetes are associated with the risk of NonB/C-HCC. Elevated AST and ALT are major risk factors for NonB/C-HCC and liver-related death. Prevention and treatment of diabetes and heart disease are critical for NonB/C-HCC.
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Affiliation(s)
- Hui-Chen Wu
- Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
- Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 630 West 168th St, Room P&S 16–421E, New York, NY 10032, USA. Phone:+1-212-305-6960
| | - Wen-Juei Jeng
- Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Mei-Hung Pan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yi-Chung Hsieh
- Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, ChiayiChang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Hwai-I. Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
- Corresponding authors. Addresses: Genomics Research Center, Academia Sinica, 128 Academia Road Section 2, Taipei 115, Taiwan. Fax: +886-2-2789-8784; Phone:+886-2-2787-1308
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12
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Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F, Coppola N. Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases. J Clin Med 2021; 10:5201. [PMID: 34768721 PMCID: PMC8584565 DOI: 10.3390/jcm10215201] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/30/2021] [Accepted: 11/03/2021] [Indexed: 12/31/2022] Open
Abstract
Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.
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Affiliation(s)
- Lorenzo Onorato
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Clarissa Camaioni
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Pierantonio Grimaldi
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Alessio Vinicio Codella
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Federica Calò
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
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13
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Han JJ, Chen Y, Nan YC, Yang YL. Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient: A case report. World J Clin Cases 2021; 9:8492-8497. [PMID: 34754858 PMCID: PMC8554442 DOI: 10.12998/wjcc.v9.i28.8492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/10/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) may be caused by hepatitis B virus (HBV) infection. Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen (HBsAg) level and increased anti-HBsAg antibody titer. Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC development. Here, we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.
CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level (over 2000 ng/mL) of serum alpha-fetoprotein. Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly. Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen (anti-HBcAg antibodies), an extremely high titer (1000 mIU/mL) of hepatitis B surface antibodies (anti-HBsAg antibodies, anti-HBs) and absence of detectible HBsAg. Medical records indicated that the patient had reported no history of HBV vaccination, infection or hepatitis. Therefore, to rule out latent HBV infection in this patient, a serum sample was collected then tested to detect HBV DNA, yielding a positive result. Based on the aforementioned information, the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.
CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.
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Affiliation(s)
- Jing-Jing Han
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yu Chen
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yu-Chen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi Province, China
| | - Yong-Lin Yang
- Department of Infectious Disease, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People's Hospital), Taizhou 225300, Jiangsu Province, China
- Department of General Practice, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
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14
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Lee HL, Bae SH, Lee J, Sung PS, Lee SW, Jang JW, Lee J, Choi JY, Han NI, Yoon SK. Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus. Cancer Control 2021; 28:10732748211039758. [PMID: 34569320 PMCID: PMC8481710 DOI: 10.1177/10732748211039758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND AND AIMS This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. METHODS A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. RESULTS The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002-2011 to 12% in 2012-2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III-V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. CONCLUSION Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.
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Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jaejun Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jungmin Lee
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Nam Ik Han
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea.,The Catholic Liver Research Center, College of Medicine, 37128The Catholic University of Korea, Seoul, Republic of Korea
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15
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Pak K, Ordway S, Torres D. Occult HBV Infection: A Case Series at a Military Treatment Facility. Mil Med 2021; 185:e795-e798. [PMID: 31681958 DOI: 10.1093/milmed/usz379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 09/08/2019] [Accepted: 09/10/2019] [Indexed: 01/04/2023] Open
Abstract
Occult HBV infection (OBI) is defined as the presence of detectable hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative individuals. Rarely, OBI is attributed to mutant HBV that cannot be detected by commercial assays, but most cases occur in the setting of chronic hepatitis B, particularly infection with wild-type viruses associated with strong HBV suppression. OBI is a high-risk diagnosis as it is associated with multiple complications: HBV reactivation in immunocompromised states, transmission of HBV, progression of liver disease, and hepatocellular carcinoma. The diagnosis is also easy to overlook, as the negative HBsAg in such cases can be falsely reassuring. This case series describes four male patients (mean age 51) who were diagnosed with OBI in the same military treatment facility between February 2018 and October 2018. Two of the four patients were active duty service members at the time of diagnosis. These patients had variable clinical presentations and outcomes. This case series illustrates the clinical significance of OBI and the importance of screening for OBI in HBsAg negative patients with signs of chronic or severe hepatic inflammation. It also prompts an intriguing question regarding the prevalence of both HBV and OBI in the United States military and whether or not routine screening for HBV should be implemented in this population. Further study is warranted to determine if adding HBV core antibody to a universally employed screening regimen would be beneficial.
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Affiliation(s)
- Kevin Pak
- Department of Internal Medicine, WRNMMC, 8901 Rockville Pike, Bethesda, MD 20889
| | - Sarah Ordway
- Division of Gastroenterology, Department of Internal Medicine, WRNMMC, 8901 Rockville Pike, Bethesda, MD 20889
| | - Dawn Torres
- Division of Gastroenterology, Department of Internal Medicine, WRNMMC, 8901 Rockville Pike, Bethesda, MD 20889
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16
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Pisaturo M, Onorato L, Russo A, Coppola N. Prevalence of occult HBV infection in Western countries. J Med Virol 2020; 92:2917-2929. [PMID: 32275083 DOI: 10.1002/jmv.25867] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
Due to a lack of standardized tests, it is difficult to obtain prevalence data and define the real impact of occult HBV infection (OBI) in Western countries. The present review article addresses the prevalence of OBI, defined as presence of hepatitis B virus (HBV) DNA in liver tissue or plasma in HBsAg-negative subjects, in Western countries. This varies in different studies according to the different methodologies used (based on serology vs virology), to the sample analyzed for the diagnosis (liver tissue vs plasma), to the different populations studied, to the different geographical variations in the HBV spread, to the host characteristics (age, gender, risk factors for acquiring HBV infection) and to the presence of other parenteral infections (hepatitis C virus and/or human immunodeficiency virus [HIV] infections). Considering the different liver diseases analyzed, that is in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges 4% to 38%. Considering the different populations studied, in the case of parenteral blood exposure it is about 45%, in patients with chronic hepatitis C it is estimated at about 52%, in HIV-infected patients it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients it ranges from 0% to 54%. In conclusion, OBI is a virological entity to be considered when performing the patient's evaluation for immunosuppressive diseases, liver pathologies, or for blood transfusions. Knowing the prevalence and clinical impact of OBI will allow better patient management.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine-Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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17
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Pisaturo M, Onorato L, Russo A, Chiodini P, Coppola N. An estimation of the prevalence of occult HBV infection in Western Europe and in Northern America: A meta-analysis. J Viral Hepat 2020; 27:415-427. [PMID: 31834645 DOI: 10.1111/jvh.13248] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 11/05/2019] [Accepted: 11/30/2019] [Indexed: 12/12/2022]
Abstract
Data on the prevalence of occult HBV infection (OBI) in Western Europe and in Northern America are few; hence, we conducted a systematic review and meta-analysis. All studies included had to fulfil the following inclusion criteria: (a) they investigated the prevalence of OBI (HBV DNA in liver tissue in HBsAg-negative subjects), (b) were carried out in Western Europe and in Northern America; (c) were available as a full-text manuscript, (d) written in English and (e) published up to December 2018. The exclusion criteria were as follows: (a) meta-analyses, letters, reviews, meeting abstracts or editorial comments; (b) studies investigating HBsAg-positive patients; (c) those investigating OBI outside Western Europe and in Northern America; and (d) to avoid small sample bias in the random-effects model, those enrolling less than five subjects. Thirty-four studies met the inclusion criteria, allowing a meta-analysis on 2729 patients. The overall prevalence of OBI was 34% (95% CI = 26%-42%), 28% (CI 95%: 12%-48%) in 329 subjects without chronic liver disease and 35% (95% CI 26%-44%) in 2400 patients with chronic liver disease. The prevalence of OBI was 51% (95% CI 40%-62%) in the 823 anti-HBc-positive subjects and 19% (95% CI 10%-30%) in the 1,041 anti-HBc-negative subjects. Evaluating the data from 17 studies comparing anti-HBc-positive and negative subjects, the prevalence of OBI was higher in the 641 anti-HBc-positive subjects than in the 1041 anti-HBc-negative (prevalence ratio = 2.29; 95% CI = 1.61-3.26, P < .001). This meta-analysis showed that in HBsAg-negative subjects the prevalence of OBI was high and was associated with anti-HBc positivity.
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Affiliation(s)
- Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Paolo Chiodini
- Department of Mental Health and Public Medicine - Medical Statistics Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy
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Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2020; 48:7-17. [PMID: 31347138 DOI: 10.1007/s15010-019-01345-y] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and a leading cause of cancer-related deaths worldwide. The major risk factors for HCC development are chronic liver disease and cirrhosis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity. RESULTS In Western countries, the number of NASH-related HCC cases is increasing, that of HBV- or HCV-related cases is declining due to the wide application of HBV universal vaccination and the introduction of effective therapies against HBV and HCV infections, and that of alcohol-related cases remaining substantially unchanged. Nevertheless, the burden of HCC is expected to increase worldwide in the next few decades, due to the population growth and aging expected in coming years. Overall, the abovementioned changes and future variations in lifestyle and in the impact of environmental factors in Western countries and a decreasing exposure to dietary aflatoxins and improved socio-economic conditions in developing countries will create new HCC epidemiology in the next few decades. CONCLUSION A substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.
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Affiliation(s)
- Evangelista Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy.
| | - Margherita Macera
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Antonio Russo
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Caterina Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
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Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV). Viruses 2019; 11:v11090850. [PMID: 31540223 PMCID: PMC6784257 DOI: 10.3390/v11090850] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/02/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022] Open
Abstract
The US Food and Drug Administration issued a black box warning related to the risk of reactivation of overt/occult hepatitis B virus (HBV) infection during direct acting-antivirals (DAA) treatment. This review evaluated the prevalence of HBV reactivation after hepatitis C virus (HCV) pharmacological suppression and hypothesized the management and prevention of this reactivation. During and after DAA-based treatment, reactivation of HBV infection is common in patients with detectable serum HBsAg (from 2% to 57%) and very low (less than 3%) in individuals with isolated anti-HBc antibodies. The severity of hepatic damage may range from HBV reactivation without hepatitis to fulminant hepatic failure requiring liver transplantation. Thus, HBsAg-positive patients should receive nucleo(s)tide analog (NA) treatment or prophylaxis at the same time as DAA therapy. For those patients with occult B infection, there are no sufficient recommendations to start prophylactic treatment. Reactivation of overt or occult HBV infection during or after eradication of HCV infection is an issue to consider, and additional studies would help to determine the best management of this virological and clinical event.
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Sagnelli C, Sagnelli E. Towards the worldwide eradication of hepatitis B virus infection: A combination of prophylactic and therapeutic factors. World J Clin Infect Dis 2019; 9:11-22. [DOI: 10.5495/wjcid.v9.i2.11] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/10/2019] [Accepted: 07/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is still a global health problem, mostly because of the intermediate/high rates of HBV chronic carriers living in most Asian, African and eastern European countries. The universal HBV vaccination of new-borns undertaken in most nations over the last 3 decades and effective HBV antiviral treatments (nucleos(t)ide analogue with high genetic barrier to viral resistance) introduced in the last decade have shown their beneficial effects in inducing a clear reduction of HBV endemicity in the countries where they have been extensively applied. Great hopes are now placed on new antiviral and immunotherapeutic drugs that are now at an advanced stage of study. It is in fact already conceivable that the synergistic use of new drugs targeting more than one HBV-lifecycle steps (covalent closed circular DNA destruction/silencing, HBV entry inhibitors, nucleocapsid assembly modulators targeting viral transcripts) and of some new immunotherapeutic agents might eliminate the intrahepatic covalent closed circular DNA and achieve the eradication of HBV infection. In spite of this, a strong effort should be given to extensive educational and screening programs for the at-risk population and to the implementation of HBV vaccination in developing countries.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80131, Italy
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Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71:397-408. [PMID: 31004683 DOI: 10.1016/j.jhep.2019.03.034] [Citation(s) in RCA: 335] [Impact Index Per Article: 55.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/20/2019] [Accepted: 03/28/2019] [Indexed: 02/06/2023]
Abstract
In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
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Affiliation(s)
- Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory at the Doherty Institute, Melbourne, Victoria, Australia
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, University of Messina, Messina, Italy; Department of Human Pathology, University of Messina, Messina, Italy
| | - Massimo Levrero
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Fabien Zoulim
- Cancer Research Center of Lyon, INSERM U1052, Hospices Civils de Lyon, Lyon University, Lyon, France
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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Sagnelli C, Pisaturo M, Calò F, Martini S, Sagnelli E, Coppola N. Reactivation of hepatitis B virus infection in patients with hemo-lymphoproliferative diseases, and its prevention. World J Gastroenterol 2019; 25:3299-3312. [PMID: 31341357 PMCID: PMC6639550 DOI: 10.3748/wjg.v25.i26.3299] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/10/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Salvatore Martini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples 80127, Italy
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Wu SS, Shan QY, Xie WX, Chen B, Huang Y, Guo Y, Xie XY, Lu MD, Peng BG, Kuang M, Shen SL, Wang W. Outcomes after hepatectomy of patients with positive HBcAb Non-B Non-C hepatocellular carcinoma compared to overt hepatitis B virus hepatocellular carcinoma. Clin Transl Oncol 2019; 22:401-410. [PMID: 31172445 DOI: 10.1007/s12094-019-02141-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 05/21/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Hepatitis B core antibody (HBcAb) positivity is regarded as a sensitive marker for occult and prior hepatitis B virus (HBV) infection. However, the prognosis of patients with HBcAb-positive in non-B, non-C hepatocellular carcinoma (NBNC-HCC) remains unclear. The study aimed to compare the clinicopathological characteristics of patients with HBcAb-positive NBNC-HCC to those with overt HBV (hepatitis B surface antigen positive) HCC. METHODS 306 HCC patients underwent hepatectomy were divided into two groups: an overt HBV-HCC group and HBcAb-positive NBNC-HCC group. Then patients were analyzed using propensity score matching (PSM) to reduce selection bias. Clinicopathological characteristics and survival outcomes were compared between the two groups. Univariate and multivariate analysis for risk factors were also evaluated. RESULTS HBcAb-positive NBNC-HCC group showed comparable survival outcomes to the overt HBV-HCC group (3-year overall survival rates 66% vs 62%, 69% vs 53%; 3-year recurrence-free survival rates 49% vs 40%, 47% vs 37%; P > 0.05) before and after PSM. Patients with HBcAb-positive NBNC-HCC were older, had more complications, higher proportions of vascular invasion, and larger tumor sizes but lower proportions of cirrhosis, elevated alanine aminotransferase and prothrombin time. CONCLUSIONS HBcAb-positive NBNC-HCC group had more advanced tumors, but their prognosis was relatively comparable to that of the other group. Therefore, we believe that screening is also necessary in HBcAb-positive patients for early detection of HCC, especially in the elderly.
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Affiliation(s)
- Shan-Shan Wu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Quan-Yuan Shan
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wen-Xuan Xie
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bin Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yang Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yu Guo
- Department of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bao-Gang Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shun-Li Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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Muche M, Berg T, Rimpler S, Staedtler A, Böhm S, Nickel P, Baid-Agrawal S. Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients. Liver Int 2019; 39:263-270. [PMID: 30171739 DOI: 10.1111/liv.13951] [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] [Received: 05/04/2018] [Revised: 08/09/2018] [Accepted: 08/12/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). METHODS HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). RESULTS Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. CONCLUSIONS We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.
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Affiliation(s)
- Marion Muche
- Department of Gastroenterology and Hepatology, Charité Universitaetsmedizin Berlin, Berlin, Germany
| | - Thomas Berg
- Section Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Sunda Rimpler
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Adrienne Staedtler
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Stefan Böhm
- Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology, Ludwig-Maximilians-Universität, Munich, Germany
| | - Peter Nickel
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany
| | - Seema Baid-Agrawal
- Department of Nephrology and Medical Intensive Care, Charite Universitaetsmedizin Berlin, Berlin, Germany.,Department of Nephrology and Transplant Center, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
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Pisaturo M, Di Caprio G, Calò F, Portunato F, Martini S, Coppola N. Management of HBV reactivation in non-oncological patients. Expert Rev Anti Infect Ther 2019; 16:611-624. [PMID: 30058401 DOI: 10.1080/14787210.2018.1505501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION HBV reactivation (HBVr) in patients undergoing immunosuppressive therapy is a well-known event. While there are clear directives on the management of current or resolved HBV infection in onco-hematological diseases, there are few data regarding patients with non-oncological diseases. Thus, the aim of the present review is to evaluate HBVr in patients with non-oncological diseases, and identify the management of these patients to prevent HBVr. Areas covered: Original papers, case reports and meta-analyses reporting data on HBVr of current or resolved infection in gastrointestinal, dermatological, rheumatologic and neurological diseases were evaluated. Expert commentary: In HBsAg-positive subjects, those with HBV-related hepatitis (both HBeAg-positive or negative) should be treated with a high genetic barrier nucleos(t)ide analog. The patients with HBV-infection (both HBeAg-positive and negative) an antiviral prophylaxis should be used, with lamivudine in those HBeAg-negative without signs of advanced liver disease, and with ETV, TDF or TAF in all the HBeAg-positive or in those HBeAg-negative with signs of advanced liver disease. In HBsAg-negative/anti-HBc positive subjects, when the risk of HBV reactivation is moderate (use of B-cell depleting agents), a prophylaxis-strategy may be considered; instead, in those with low risk of HBVr, a pre-emptive therapy strategy may be used.
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Affiliation(s)
- Mariantonietta Pisaturo
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Giovanni Di Caprio
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Federica Calò
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Federica Portunato
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy
| | - Salvatore Martini
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy.,b Section of Infectio us Diseases , A.O.R.N. Dei Colli, Cotugno Hospital , Napoli , Italy
| | - Nicola Coppola
- a Department of Mental Health and Public Medicine, Section of Infectious Diseases , University of Campania , Naples , Italy.,c Section of Infectious Diseases , A.O.R.N S.Anna S. Sebastiano Caserta , Caserta , Italy
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Tong MJ, Theodoro CF, Salvo RT. Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance. J Dig Dis 2018; 19:411-420. [PMID: 29889353 DOI: 10.1111/1751-2980.12615] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/25/2018] [Accepted: 06/07/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies. METHODS We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years. RESULTS Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04). CONCLUSIONS The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.
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Affiliation(s)
- Myron J Tong
- Liver Center, Huntington Medical Research Institutes, Pasadena, California, USA.,Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | | | - Rebecca T Salvo
- Liver Center, Huntington Medical Research Institutes, Pasadena, California, USA
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Coppola N, Onorato L, Panella M, de Stefano G, Mosca N, Minichini C, Messina V, Potenza N, Starace M, Alessio L, Farella N, Sagnelli E, Russo A. Correlation Between the Hepatic Expression of Human MicroRNA hsa-miR-125a-5p and the Progression of Fibrosis in Patients With Overt and Occult HBV Infection. Front Immunol 2018; 9:1334. [PMID: 29951066 PMCID: PMC6008383 DOI: 10.3389/fimmu.2018.01334] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 05/29/2018] [Indexed: 12/16/2022] Open
Abstract
Aims To evaluate the correlation between the hepatic expression pattern of hsa-miR-125a-5p and HBV-DNA and the progression of fibrosis in patients with overt or occult HBV infection. Methods We enrolled all the HBsAg-positive treatment naive patients (overt HBV group) and all the HBsAg-negative patients with hepatocellular carcinoma and with a positive HBV-DNA in their hepatic tissue (occult HBV group), who underwent a diagnostic liver biopsy between April 2007 and April 2015. Tissue concentrations of HBV-DNA and hsa-miR-125a-5p were then analyzed by real-time quantitative PCR. Necroinflammatory activity and fibrosis were evaluated according to the Ishak score. Results During the study period, we enrolled 64 patients with overt and 10 patients with occult HBV infection. In the overt HBV group, 35 of 64 (54.7%) showed a mild fibrosis (staging 0–2), 17 (26.6%) a moderate fibrosis (staging 3–4), while the remaining 12 (18.7%) had a cirrhosis. All patients in the occult HBV group were cirrhotic. Patients with more advanced fibrosis stage showed a higher mean age when compared with those with mild (p < 0.00001) or moderate fibrosis (p < 0.00001) and were more frequently male than patients with staging 0–2 (p = 0.04). Similarly, patients with occult B infection were older than HBsAg-positive patients. Liver concentrations of miR-125a-5p were significantly higher in patients with cirrhosis (9.75 ± 4.42 AU) when compared with patients with mild (1.39 ± 0.94, p = 0.0002) or moderate fibrosis (2.43 ± 2.18, p = 0.0006) and were moderately higher in occult than in overt HBV infection (p = 0.09). Moreover, we found an inverse correlation, although not statistically significant, between the tissue HBV-DNA levels and the staging of fibrosis. Conclusion This study suggests a correlation between the tissue expression of hsa-miR-125a-5p and the progression of liver damage in a group of patients with occult or overt HBV infection. If confirmed, these data suggest the hsa-miR-125a-5p may be a novel biomarker of hepatic damage.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy.,Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - Marta Panella
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Caserta, Italy
| | - Giorgio de Stefano
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy
| | - Nicola Mosca
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Caserta, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - Vincenzo Messina
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Nicoletta Potenza
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Caserta, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - Loredana Alessio
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Nunzia Farella
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - Aniello Russo
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Caserta, Italy
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Ling Q, Liu J, Zhuo J, Zhuang R, Huang H, He X, Xu X, Zheng S. Development of models to predict early post-transplant recurrence of hepatocellular carcinoma that also integrate the quality and characteristics of the liver graft: A national registry study in China. Surgery 2018; 164:S0039-6060(18)30079-5. [PMID: 29709370 DOI: 10.1016/j.surg.2018.01.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 01/11/2018] [Accepted: 01/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Donor characteristics and graft quality were recently reported to play an important role in the recurrence of hepatocellular carcinoma after liver transplantation. Our aim was to establish a prognostic model by using both donor and recipient variables. METHODS Data of 1,010 adult patients (training/validation: 2/1) undergoing primary liver transplantation for hepatocellular carcinoma were extracted from the China Liver Transplant Registry database and analyzed retrospectively. A multivariate competing risk regression model was developed and used to generate a nomogram predicting the likelihood of post-transplant hepatocellular carcinoma recurrence. RESULTS Of 673 patients in the training cohort, 70 (10.4%) had hepatocellular carcinoma recurrence with a median recurrence time of 6 months (interquartile range: 4-25 months). Cold ischemia time was the only independent donor prognostic factor for predicting hepatocellular carcinoma recurrence (hazard ratio = 2.234, P = .007). The optimal cutoff value was 12 hours when patients were grouped according to cold ischemia time at 2-hour intervals. Integrating cold ischemia time into the Milan criteria (liver transplantation candidate selection criteria) improved the accuracy for predicting hepatocellular carcinoma recurrence in both training and validation sets (P < .05). A nomogram composed of cold ischemia time, tumor burden, differentiation, and α-fetoprotein level proved to be accurate and reliable in predicting the likelihood of 1-year hepatocellular carcinoma recurrence after liver transplantation. Additionally, donor anti-hepatitis B core antibody positivity, prolonged cold ischemia time, and anhepatic time were linked to the intrahepatic recurrence, whereas older donor age, prolonged donor warm ischemia time, cold ischemia time, and ABO incompatibility were relevant to the extrahepatic recurrence. CONCLUSION The graft quality integrated models exhibited considerable predictive accuracy in early hepatocellular carcinoma recurrence risk assessment. The identification of donor risks can further help understand the mechanism of different patterns of recurrence.
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Affiliation(s)
- Qi Ling
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Jimin Liu
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Jianyong Zhuo
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Runzhou Zhuang
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haitao Huang
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | | | - Xiao Xu
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China; China Liver Transplant Registry, Hangzhou, China
| | - Shusen Zheng
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China; China Liver Transplant Registry, Hangzhou, China.
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Marrone A, Capoluongo N, D'Amore C, Pisaturo M, Esposito M, Guastafierro S, Siniscalchi I, Macera M, Boemio A, Onorato L, Rinaldi L, Minichini C, Adinolfi LE, Sagnelli E, Mastrullo L, Coppola N. Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy. J Viral Hepat 2018; 25:198-204. [PMID: 29029365 DOI: 10.1111/jvh.12802] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Accepted: 08/31/2017] [Indexed: 12/11/2022]
Abstract
This study evaluated the long-term efficacy and safety of an 18-month lamivudine prophylaxis in 68 HBsAg-negative/anti-HBc-positive patients with oncohaematological disease. All 68 consecutive HBsAg-negative/anti-HBc-positive patients with an oncohaematological disease and naïve for chemotherapy observed from April 2008 to December 2012 at 2 Hematology Units in Naples were treated with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg at months 1 and 3 during chemotherapy and then every 3 months after its discontinuation. During follow-up, 13 (19.1%) of the 68 patients died of complications related to their oncohaematological disease, and 3 (4%) showed a virological HBV reactivation (retroconversion to HBsAg positivity) 1-7 months after the discontinuation of lamivudine prophylaxis (2 treated for chronic lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a biochemical reactivation. Comparing the demographic and clinical characteristics of the 3 patients with a virological HBV reactivation to the 65 without, the former were older (median age and range: 67 years [75-78] vs. 61 [24-88]; P = .05) and were less frequently treated for B-cell non-Hodgkin lymphoma (B-NHL) (0 vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was effective in preventing HBV reactivation in HBsAg-negative/anti-HBc-positive patients treated for B-NHL. However, in patients with chronic and severe immunodepression, such as those with chronic lymphocytic leukaemia and Waldenstrom's disease, prophylaxis should be continued for an indefinite period.
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Affiliation(s)
- A Marrone
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - N Capoluongo
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - C D'Amore
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - M Pisaturo
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - M Esposito
- Hematology Unit, Ascalesi Hospital, Naples, Italy
| | - S Guastafierro
- Hematology Unit, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - I Siniscalchi
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - M Macera
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - A Boemio
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - L Onorato
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - L Rinaldi
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - C Minichini
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - L E Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - E Sagnelli
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
| | - L Mastrullo
- Hematology Unit, Ascalesi Hospital, Naples, Italy
| | - N Coppola
- Department of Mental Health and Public Medicine, University of Campania, Luigi Vanvitelli, Naples, Italy
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Tan CHN, Soon GST, Kow WCA. Liver lesions detected in a hepatitis B core total antibody-positive patient masquerading as hepatocellular carcinoma: a rare case of peliosis hepatis and a review of the literature. Ann Hepatobiliary Pancreat Surg 2017; 21:157-162. [PMID: 28990003 PMCID: PMC5620477 DOI: 10.14701/ahbps.2017.21.3.157] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 03/01/2017] [Accepted: 03/04/2017] [Indexed: 12/24/2022] Open
Abstract
Peliosis Hepatis (PH) is a rare vascular disorder of the liver, characterized by the presence of cystic blood-filled cavities distributed throughout the hepatic parenchyma. The pathogenesis of PH remains controversial. The preoperative diagnosis of PH is difficult, due to the non-specific imaging characteristics of PH and almost all cases are diagnosed on histology post resection. This study presents a case of PH masquerading as hepatocellular carcinoma (HCC). The patient is a 45-year old Chinese lady, who presented with transaminitis. She was found to be hepatitis B virus core total antibody-positive with an alpha-fetoprotein (AFP) of 29.4 ng/ml. Triphasic liver computed tomography showed several arterial hypervascular lesions and hypoenhancing lesions on the venous phase, particularly in the segments 6/7. Subsequently, a magnetic resonance imaging scan showed multiple lesions in the right hemiliver with an indeterminate enhancement patterns. Subsequently, she decided to undergo a resection procedure. Histopathology revealed findings consistent with PH with some unusual features. This case demonstrates a clinical conundrum, in which PH presented with a raised AFP, in a patient with risk factors for the development of HCC. The clinical suspicion of PH should be high in patients, who present with multiple hepatic lesions with variable enhancement patterns.
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Affiliation(s)
- Chun Han Nigel Tan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | | | - Wei Chieh Alfred Kow
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore
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HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian Patients With Liver Cirrhosis. Am J Gastroenterol 2017; 112:1111-1119. [PMID: 28440303 DOI: 10.1038/ajg.2017.123] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 03/14/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes. METHODS This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox's proportional hazards models. RESULTS After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6-96.8%) vs. 36.2% (95% CI: 28.7-39.1%) for those with cirrhosis (P<0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33-3.39), P<0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56-2.27) and 2.34 (1.12-4.86), respectively. CONCLUSIONS Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.
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Lee MH, Huang CF, Lai HC, Lin CY, Dai CY, Liu CJ, Wang JH, Huang JF, Su WP, Yang HC, Kee KM, Yeh ML, Chuang PH, Hsu SJ, Huang CI, Kao JT, Chen CC, Chen SH, Jeng WJ, Yang HI, Yuan Y, Lu SN, Sheen IS, Liu CH, Peng CY, Kao JH, Yu ML, Chuang WL, Chen CJ. Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients. Sci Rep 2017; 7:3718. [PMID: 28623331 PMCID: PMC5473811 DOI: 10.1038/s41598-017-02313-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 04/10/2017] [Indexed: 12/23/2022] Open
Abstract
This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004-2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22-0.63) for those without cirrhosis and 0.54 (0.31-0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jung-Ta Kao
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Juei Jeng
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, NJ, USA
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
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