|
1
|
Sugiyama Y, Tahara N, Honda A, Koga Y, Yoshimura-Takubo H, Bekki M, Tahara A, Maeda-Ogata S, Igata S, Mizushima Y, Murotani K, Kuromatsu R, Kawaguchi T, Fukumoto Y. Utility of liver stiffness for the classification of portopulmonary hypertension in precapillary pulmonary hypertension. Int J Cardiol 2025; 429:133126. [PMID: 40058610 DOI: 10.1016/j.ijcard.2025.133126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 12/15/2024] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Invasive right heart catheterization plays a central role in identifying pulmonary hypertension (PH) disorders. However, non-invasive biomarkers of portopulmonary hypertension (PoPH) are required. Liver stiffness evaluated by FibroScan® is useful for the assessment of liver fibrosis in patients with chronic liver diseases. This study sought to investigate the utility of liver stiffness for the classification of PoPH among precapillary PH patients. METHODS A total of 46 patients [38 females, median (interquartile range) age 63.0 (50.8-72.0) years old] with precapillary PH were divided into a PoPH group (N = 6) and a non-PoPH group (N = 40) based on the presence of portosystemic shunts and/or portal hypertension with hepatic venous pressure gradient >5 mmHg. RESULTS The PoPH group showed higher cardiac index and lower pulmonary vascular resistance than the non-PoPH group. Other hemodynamic variables and liver fibrosis biomarkers such as fibrosis-4 index and albumin-bilirubin score were comparable between the 2 groups. Liver stiffness measurements in the PoPH group were significantly higher than those in the non-PoPH group [12.8 kPa (9.4-17.3 kPa) vs 4.15 kPa (3.30-5.50 kPa), p < 0.001]. The cut-off value for the classification of PoPH was 8.50 kPa from the receiver operating characteristic curve (area under curve 0.979, 95 % Confidence interval 8.50 kPa - 11.00 kPa). CONCLUSIONS Liver stiffness evaluated by transient elastography may be a non-invasive biomarker to detect the liver status that caused PoPH among precapillary PH patients.
Collapse
Affiliation(s)
- Yoichi Sugiyama
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan.
| | - Nobuhiro Tahara
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan.
| | - Akihiro Honda
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Yuki Koga
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Harumi Yoshimura-Takubo
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Munehisa Bekki
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Atsuko Tahara
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Shoko Maeda-Ogata
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Sachiyo Igata
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Yasuko Mizushima
- Ultrasound Diagnostic Center, Kurume University Hospital, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Kenta Murotani
- Biostatistics Center, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan; School of Medical Technology, Kurume University, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Ryoko Kuromatsu
- Ultrasound Diagnostic Center, Kurume University Hospital, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology Medicine, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume 830-0011, Japan
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, 67 Asahi-Machi, Kurume 830-0011, Japan
| |
Collapse
|
|
2
|
Silva CLM, Puthanveetil PN, Oliveira SD. Liver bypass in the development of pathogen-associated pulmonary vascular disease: contribution of mesocaval and portosystemic shunts. Am J Physiol Gastrointest Liver Physiol 2025; 328:G791-G800. [PMID: 40323787 DOI: 10.1152/ajpgi.00409.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/18/2025] [Accepted: 04/24/2025] [Indexed: 05/07/2025]
Abstract
Portosystemic and mesocaval shunts are aberrant vascular connections that bypass hepatic detoxification process, directly linking the portal to the systemic circulation. These shunts, whether congenital or acquired, might play a pivotal role in the pathogenesis of systemic inflammatory diseases, such as schistosomiasis-associated pulmonary hypertension (Sch-PH) by facilitating the dissemination of pathogen-derived eggs and antigens from the gut and mesentery into the lungs. Beyond the translocation of Schistosoma mansoni eggs, emerging evidence implicates that gut-lung microbiome dysbiosis contributes to the development of pulmonary hypertension (PH) in the preclinical animal model of Sch-PH. Sch-PH emerges as a chronic complication of schistosomiasis and evolves silently, progressively increasing the mean pulmonary arterial pressure and vascular resistance, leading to right heart hypertrophy, failure, and significant morbidity and mortality. Chronic schistosomiasis is often linked to the development of portal hypertension, which significantly contributes to the formation of the porto/mesocaval shunt as a compensatory response that can have far-reaching implications on pulmonary vascular physiology. In addition, portal hypertension compromises the integrity of the intestinal barrier, exacerbating peritoneal and mesenteric inflammation, potentially facilitating microbial and metabolite entrance into the systemic circulation. This article briefly discusses the mechanisms by which porto/mesocaval shunts contribute to PH, especially Group I PH, focusing on the interplay between portosystemic shunting, microbial translocation, and systemic dissemination of proinflammatory metabolites.
Collapse
Affiliation(s)
- Claudia Lucia Martins Silva
- Biochemical and Molecular Pharmacology Laboratory, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Prasanth N Puthanveetil
- Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, United States
- Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, United States
| | - Suellen Darc Oliveira
- Vascular Immunobiology Laboratory, Department of Anesthesiology, College of Medicine, University of Illinois Chicago, Chicago, Illinois, United States
- Vascular Immunobiology Laboratory, Department of Physiology and Biophysics, University of Illinois Chicago, Chicago, Illinois, United States
| |
Collapse
|
|
3
|
Adel F, Kabbara Allababidi A, Reddy YNV. Hepatopulmonary Syndrome or Portopulmonary Hypertension? Two Contrasting Cases of Exertional Hypoxemia From Liver Disease. Circ Heart Fail 2025:e012506. [PMID: 40084409 DOI: 10.1161/circheartfailure.124.012506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Affiliation(s)
- Fadi Adel
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | | | - Yogesh N V Reddy
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| |
Collapse
|
|
4
|
El Koofy N, Okasha SH, Agha HM, Ali N, Behairy AS, Fouad HM, Zawam RH. Prevalence and Predictors of Pulmonary Hypertension in Children with Portal Hypertension: A Single Center Study. Pediatr Gastroenterol Hepatol Nutr 2025; 28:101-112. [PMID: 40109566 PMCID: PMC11919534 DOI: 10.5223/pghn.2025.28.2.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/26/2024] [Accepted: 12/18/2024] [Indexed: 03/22/2025] Open
Abstract
Purpose This study aimed to estimate the prevalence and predictors of portopulmonary hypertension (POPH) in children with portal hypertension. Methods We recruited children of both sexes aged 3-15 years with portal hypertension that was clinically suspected and confirmed by the presence of varices on esophagogastroduodenoscopy (EGD). The participants underwent clinical examination, 6-min walk distance (6-MWD), and echocardiography. Results We enrolled 94 children with portal hypertension: 26.6% with pre-hepatic causes and 73.4% secondary to chronic liver disease. Among our participants, 13.8% had one or more cardiac manifestations, such as exercise intolerance, dyspnea on exertion, cyanosis, or orthopnea, whereas 86.2% were asymptomatic. EGD examination revealed grade I varices in 54.3% of cases, grade II-III in 43.6%, and grade IV in 2.1%. Pulmonary hypertension (>35 mmHg) was detected in 30.9% of cases using echocardiography; two of them were >45 mmHg. Patients with POPH had significantly more frequent dyspnea on exertion, lower O2 saturation, and more severe variceal grades than those with normal pulmonary artery pressure. Five (6.9%) cases had <300 m 6-MWD, with no significant difference between patients with normal and those with elevated pulmonary artery pressure. The duration of portal hypertension and 6-MWD were correlated significantly with the echocardiographic measures. High-grade varices (p=0.04) and low O2 saturation (p=0.03) were identified as risk factors for POPH. Conclusion POPH was detected in 30.9% of our study group. High-grade varices and low O2 saturation are predictors of POPH. Echocardiography screening is crucial for the early detection of cases.
Collapse
Affiliation(s)
- Nehal El Koofy
- Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Hala Mounir Agha
- Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Noha Ali
- Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Said Behairy
- Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hanan Mina Fouad
- Department of Pediatric, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Rehab Hamdy Zawam
- Department of Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt
| |
Collapse
|
|
5
|
Dzikowska-Diduch O, Cader T, Jankowski K, Ou-Pokrzewińska A, Sznajder M, Siwiec J, Pucyło S, Sikora A, Pacholczyk M, Lisik W, Pruszczyk P, Kurnicka K. Echocardiographic Screening of Liver Transplant Candidates-Prevalence of Features of Portopulmonary Hypertension. J Clin Med 2024; 13:6990. [PMID: 39598134 PMCID: PMC11594917 DOI: 10.3390/jcm13226990] [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: 09/29/2024] [Revised: 11/07/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Background: The prevalence of portopulmonary hypertension (PoPH) is relatively low; however, its presence significantly worsens patients' prognosis. When diagnosed, PoPH can be effectively treated, and specific therapies can lead to a substantial reduction in pulmonary circulation pressure, facilitating the safe performance of liver transplantation. Echocardiography is recommended as a first-line method for the non-invasive diagnosis of pulmonary hypertension and serves as a valuable screening tool for patients being evaluated for liver transplantation (LT). The objective of this study was to thoroughly assess the occurrence of echocardiographic signs indicative of pulmonary hypertension and hepatopulmonary syndrome (HPS) in candidates for LT. We assumed that our analysis also made it possible to assess how frequently these candidates require further invasive diagnostics for pulmonary hypertension at specialized centers and how often they may need targeted treatment for pulmonary arterioles as a bridge to transplantation, which could improve patient outcomes. Additionally, this study included a comprehensive review of the current literature. Methods: All LT candidates underwent standardized transthoracic echocardiography and contrast evaluation to identify intrapulmonary vascular shunts. Results: A total of 152 liver transplantation candidates (67 women, mean age 50.6 years) were included in the analysis. The estimated echocardiographic probability of pulmonary hypertension was classified as high in only one patient. However, 63 patients exhibited the visualization of microbubbles in the left heart chambers after an average of six cardiac cycles (ranging from three to nine cycles) following their appearance in the right heart. Conclusions: Our analysis shows that the features of PoPH and a high probability of PH were very rare in the LT candidates, and echocardiographic signs suggestive of hepatopulmonary syndrome were more prevalent. Liver transplant candidates need screening for PoPH and HPS, as both PoPH and HPS significantly worsen their prognosis, but specific PH treatment as a bridge to transplantation improves PoPH patients' survival.
Collapse
Affiliation(s)
- Olga Dzikowska-Diduch
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Tomasz Cader
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Krzysztof Jankowski
- Department of Social Medicine and Public Health, Medical University of Warsaw, 02-106 Warsaw, Poland;
| | - Aisha Ou-Pokrzewińska
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Monika Sznajder
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Jan Siwiec
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Szymon Pucyło
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Aleksandra Sikora
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Marek Pacholczyk
- Department of General and Transplant Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.P.); (W.L.)
| | - Wojciech Lisik
- Department of General and Transplant Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; (M.P.); (W.L.)
| | - Piotr Pruszczyk
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| | - Katarzyna Kurnicka
- Department of Internal Medicine & Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (O.D.-D.); (A.O.-P.); (M.S.); (J.S.); (S.P.); (A.S.); (P.P.); (K.K.)
| |
Collapse
|
|
6
|
Kawut SM, Feng R, Ellenberg SS, Zamanian R, Bull T, Chakinala M, Mathai SC, Hemnes A, Lin G, Doyle M, Andrew R, MacLean M, Stasinopoulos I, Austin E, DeMichele A, Shou H, Minhas J, Song N, Moutchia J, Ventetuolo CE. Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Respir Crit Care Med 2024; 210:1143-1151. [PMID: 38747680 PMCID: PMC11544352 DOI: 10.1164/rccm.202402-0371oc] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 05/15/2024] [Indexed: 11/02/2024] Open
Abstract
Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; P = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).
Collapse
Affiliation(s)
- Steven M Kawut
- Department of Medicine
- Department of Biostatistics, Epidemiology, and Informatics, and
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rui Feng
- Department of Biostatistics, Epidemiology, and Informatics, and
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan S Ellenberg
- Department of Biostatistics, Epidemiology, and Informatics, and
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Roham Zamanian
- Department of Medicine, Stanford University, Stanford, California
| | - Todd Bull
- Pulmonary Vascular Disease Center, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Denver, Colorado
| | - Murali Chakinala
- Department of Medicine, Washington University in St. Louis, St. Louis, Missouri
| | - Stephen C Mathai
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | | | - Grace Lin
- Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Margaret Doyle
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont
| | - Ruth Andrew
- University/British Heart Foundation, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Margaret MacLean
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; and
| | - Ioannis Stasinopoulos
- University/British Heart Foundation, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Eric Austin
- Department of Pediatrics, Vanderbilt University, Nashville, Tennessee
| | - Angela DeMichele
- Department of Medicine
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Haochang Shou
- Department of Biostatistics, Epidemiology, and Informatics, and
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Nianfu Song
- Department of Biostatistics, Epidemiology, and Informatics, and
| | - Jude Moutchia
- Department of Biostatistics, Epidemiology, and Informatics, and
| | - Corey E Ventetuolo
- Department of Medicine and
- Department of Health Services, Policy and Practice, Brown University, Providence, Rhode Island
| |
Collapse
|
|
7
|
Bommena S, Fallon MB. Pulmonary Complications of Portal Hypertension. Clin Liver Dis 2024; 28:467-482. [PMID: 38945638 DOI: 10.1016/j.cld.2024.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Portopulmonary hypertension (POPH), hepatopulmonary syndrome, and hepatic hydrothorax constitute significant complications of portal hypertension, with important implications for management and liver transplantation (LT) candidacy. POPH is characterized by obstruction and remodeling of the pulmonary resistance arterial bed. Hepatopulmonary syndrome is the most common pulmonary vascular disorder, characterized by intrapulmonary vascular dilatations causing impaired gas exchange. LT may improve prognosis in select patients with POPH. LT is the only effective treatment of hepatopulmonary syndrome. Hepatic hydrothorax is defined as transudative pleural fluid accumulation that is not explained by primary cardiopulmonary or pleural disease. LT is the definitive cure for hepatic hydrothorax.
Collapse
Affiliation(s)
- Shoma Bommena
- Department of Internal Medicine, University of Arizona College of Medicine-Phoenix, Banner University Medical Center, Phoenix, AZ, USA
| | - Michael B Fallon
- Department of Internal Medicine, University of Arizona College of Medicine-Phoenix, 475 North 5th Street, Phoenix, AZ 85004, USA.
| |
Collapse
|
|
8
|
Chooklin S, Chuklin S, Posivnych M, Krystopchuk S. Portopulmonary hypertension: peculiarities of diagnosis and treatment. EMERGENCY MEDICINE 2024; 20:146-158. [DOI: 10.22141/2224-0586.20.3.2024.1686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Portopulmonary hypertension is defined as the development of pulmonary hypertension secondary to portal one. Its exact prevalence is difficult to determine due to the lack of routine screening in patients with portal hypertension. Hemodynamic changes associated with portal hypertension, including the hyperdynamic state, portosystemic shunts, and splanchnic vasodilation, cause significant disturbances in the pulmonary vasculature and play a key role in the pathogenesis of the disease. Without treatment, portopulmonary hypertension leads to progressive right ventricular failure with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and candidates for liver transplant, right heart catheterization remains the gold standard for disease diagnosis. Treatment of patients with portopulmonary hypertension is aimed at improving cardiac function, reducing pulmonary vascular resistance, and optimizing functional capacity. Pulmonary hypertension-specific therapy, which includes prostacyclin and its receptor agonists, endothelin receptor antagonists, phosphodiesterase inhibitors, and guanylate cyclase stimulators, plays a key role in the treatment of patients with portopulmonary hypertension. Small uncontrolled and recent single randomized controlled trials have reported promising results of vasodilator therapy in terms of clinical and hemodynamic improvement in patients, allowing certain patients to undergo liver transplantation. This review discusses the epidemiology, approach to diagnosis and treatment of patients with portopulmonary hypertension. We used MEDLINE database on the PubMed platform and the Cochrane library to search for literature sources using the keywords: portopulmonary hypertension, portal hypertension, pulmonary hypertension, liver cirrhosis, pulmonary complications.
Collapse
|
|
9
|
Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
Collapse
Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
| | | |
Collapse
|
|
10
|
Singh N, Al-Naamani N, Brown MB, Long GM, Thenappan T, Umar S, Ventetuolo CE, Lahm T. Extrapulmonary manifestations of pulmonary arterial hypertension. Expert Rev Respir Med 2024; 18:189-205. [PMID: 38801029 PMCID: PMC11713041 DOI: 10.1080/17476348.2024.2361037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 05/24/2024] [Indexed: 05/29/2024]
Abstract
INTRODUCTION Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH. AREAS COVERED A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers. EXPERT OPINION Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.
Collapse
Affiliation(s)
- Navneet Singh
- Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI
| | - Nadine Al-Naamani
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Mary Beth Brown
- Department of Rehabilitation Medicine, University of Washington School of Medicine, Seattle, WA
| | - Gary Marshall Long
- Department of Kinesiology, Health and Sport Sciences, University of Indianapolis, Indianapolis, IN
| | - Thenappan Thenappan
- Section of Advanced Heart Failure and Pulmonary Hypertension, Cardiovascular Division, University of Minnesota, Minneapolis, MN
| | - Soban Umar
- Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Corey E. Ventetuolo
- Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI
- Department of Health Services, Policy and Practice, Brown University, Providence, RI
| | - Tim Lahm
- Department of Medicine, National Jewish Health, Denver, CO
- Department of Medicine, University of Colorado, Aurora, CO
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO
| |
Collapse
|
|
11
|
Vaishnav B, Barla DR, Ruchitha P, Wadivkar AN, Tonde T, Mondkar S. Pulmonary Dysfunction in Patients with Cirrhosis of the Liver: A Study of Pulmonary Function Tests and Arterial Blood Gases. Int J Appl Basic Med Res 2024; 14:48-53. [PMID: 38504842 PMCID: PMC10947758 DOI: 10.4103/ijabmr.ijabmr_367_23] [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: 08/10/2023] [Revised: 12/18/2023] [Accepted: 01/10/2024] [Indexed: 03/21/2024] Open
Abstract
Background and Aim Respiratory complications in liver cirrhosis can occur due to various mechanisms, such as ascites causing restricted lung expansion and opening of intrapulmonary vascular shunts due to high portal pressures. We aimed to study the effects of the liver dysfunction on the lungs by evaluating arterial blood gas (ABG) and pulmonary function test (PFT) of all study subjects. Subjects and Methods A cross-sectional study was done between August 2020 and September 2022. Diagnosed cases of the liver cirrhosis were enrolled in the study after informed consent and were subjected to the following investigations: chest X-ray, oximetry, spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), two-dimensional echocardiography, and ABG analysis (ABGA). The cases were divided into three groups based on their Child-Pugh staging, and statistical analysis was done on the collected data. Results A total of 64 (53 males and 11 females) patients with an average age of 49.82 ± 9.89 years were studied. Alcoholism was the most common cause of cirrhosis in males. Breathlessness (65.6%) and pleural effusion (26.6%) were the most common respiratory symptoms and signs, respectively. Seventeen patients had hepatic hydrothorax, eight patients had hepatopulmonary syndrome (HPS), and six patients had portopulmonary hypertension. Low pH (17.2%) and oxygen partial pressure (PaO2) (20.3%) were the most common ABGA findings. The pH, PaO2, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), and DLCO were significantly low in Child Pugh Stage C (P < 0.05). The pH, pO2, HCO3, FEV1, FVC, FEV1/FVC, and DLCO were significantly lower in patients with HPS (P < 0.05). Conclusion Metabolic acidosis and low FEV1/FVC and DLCO were the common findings in study subjects. Pulmonary dysfunction was common in advanced liver cirrhosis. Patients with HPS had worse ABG and PFT parameters than those without HPS.
Collapse
Affiliation(s)
- Bhumika Vaishnav
- Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
| | - Dasaradha Ramu Barla
- Department of Medicine, Gitam Institute of Medical Sciences and Research, Visakhapatnam, Andhra Pradesh, India
| | - Pailla Ruchitha
- Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
| | - Aniruddh N. Wadivkar
- Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
| | - Tushar Tonde
- Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
| | - Saish Mondkar
- Department of Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
| |
Collapse
|
|
12
|
Radchenko GD, Sirenko YM. When Pulmonary Arterial Hypertension may be Associated with Portal Hypertension: A Case Report of Two Different Hepatic Disorders in One Patient with Pulmonary Hypertension. Curr Cardiol Rev 2023; 20:CCR-EPUB-135441. [PMID: 37881075 PMCID: PMC11071676 DOI: 10.2174/011573403x267162231011154808] [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: 07/22/2023] [Revised: 08/06/2023] [Accepted: 09/23/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND pulmonary arterial hypertension (PAH) is a rare complication of hepatic diseases with portal hypertension that, however, has a significant influence on prognosis. We present a mini-review of how to diagnose and treat it based on a clinical case. CASE PRESENTATION in early childhood, a patient had portal hypertension associated with cavernous transformation of the portal vein. It was successfully treated by reno-splenic surgery. At the age of 20 years, this patient experienced increased dyspnea at minimal physical activity after the hepatic biopsy due to a hepatocellular adenoma. The examination in the specialized unit showed PAH, which was evaluated as associated with portal hypertension (PAH-PoH). The specific two-drug combination therapy was started with prominent improvement in patient's state. Successful surgical tumor treatment was provided some months later. The practical and clinical approaches to the diagnosis and treatment of PAH-PoH are discussed. It was emphasized that not all patients with portal hypertension have pulmonary hypertension, which needs to be treated. A lot of evidence gaps exist in management of these patients. CONCLUSION all patients, even with past history of portal hypertension, should be monitored closely and screened for PAH earlier, for better results of treatment.
Collapse
Affiliation(s)
- Ganna D. Radchenko
- State Institution National Scientific Center “Institute of Cardiology, Clinical and Regenerative Medicine named after acad. M.D. Strazhesko” of National Academy of Medical Science, Kyiv, Ukraine
| | - Yuriy M. Sirenko
- State Institution National Scientific Center “Institute of Cardiology, Clinical and Regenerative Medicine named after acad. M.D. Strazhesko” of National Academy of Medical Science, Kyiv, Ukraine
| |
Collapse
|
|
13
|
Boucly A, Gerges C, Savale L, Jaïs X, Jevnikar M, Montani D, Sitbon O, Humbert M. Pulmonary arterial hypertension. Presse Med 2023; 52:104168. [PMID: 37516248 DOI: 10.1016/j.lpm.2023.104168] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 07/17/2023] [Indexed: 07/31/2023] Open
Abstract
Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary vasculature. This leads to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure and, if left untreated, to right ventricular failure and death. A correct diagnosis requires a complete work-up including right heart catheterisation performed in a specialised centre. Although our knowledge of the epidemiology, pathology and pathophysiology of the disease, as well as the development of innovative therapies, has progressed in recent decades, PAH remains a serious clinical condition. Current treatments for the disease target the three specific pathways of endothelial dysfunction that characterise PAH: the endothelin, nitric oxide and prostacyclin pathways. The current treatment algorithm is based on the assessment of severity using a multiparametric risk stratification approach at the time of diagnosis (baseline) and at regular follow-up visits. It recommends the initiation of combination therapy in PAH patients without cardiopulmonary comorbidities. The choice of therapy (dual or triple) depends on the initial severity of the condition. The main treatment goal is to achieve low-risk status. Further escalation of treatment is required if low-risk status is not achieved at subsequent follow-up assessments. In the most severe patients, who are already on maximal medical therapy, lung transplantation may be indicated. Recent advances in understanding the pathophysiology of the disease have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways.
Collapse
Affiliation(s)
- Athénaïs Boucly
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France; National Heart and Lung Institute, Imperial College London, London, UK.
| | - Christian Gerges
- Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
| | - Laurent Savale
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| | - Xavier Jaïs
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| | - Mitja Jevnikar
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| | - David Montani
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| | - Olivier Sitbon
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| | - Marc Humbert
- Université Paris-Saclay, Faculé de Médicine, Le Kremlin-Bicêtre, France; Service de Pneumologie et Soins Intensifs Respiratoires, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMRS-999, Le Kremlin-Bicêtre, France
| |
Collapse
|
|
14
|
Brankovic M, Lee P, Pyrsopoulos N, Klapholz M. Cardiac Syndromes in Liver Disease: A Clinical Conundrum. J Clin Transl Hepatol 2023; 11:975-986. [PMID: 37408802 PMCID: PMC10318294 DOI: 10.14218/jcth.2022.00294] [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: 06/14/2022] [Revised: 09/28/2022] [Accepted: 11/28/2022] [Indexed: 07/03/2023] Open
Abstract
Understanding the interaction between the heart and liver is pivotal for managing patients in whom both organs are affected. Studies have shown that cardio-hepatic interactions are bidirectional and that their identification, assessment, and treatment remain challenging. Congestive hepatopathy is a condition that develops in the setting of long-standing systemic venous congestion. If left untreated, congestive hepatopathy may lead to hepatic fibrosis. Acute cardiogenic liver injury develops as a combination of venous stasis and sudden arterial hypoperfusion due to cardiac, circulatory, or pulmonary failure. The treatment of both conditions should be directed toward optimizing the cardiac substrate. Hyperdynamic syndrome may develop in patients with advanced liver disease and lead to multiorgan failure. Cirrhotic cardiomyopathy or abnormalities in pulmonary vasculature, such as hepatopulmonary syndrome and portopulmonary hypertension may also develop. Each complication has unique treatment challenges and implications for liver transplantation. The presence of atrial fibrillation and atherosclerosis in liver disease brings another layer of complexity, particularly in terms of anticoagulation and statin use. This article provides an overview of cardiac syndromes in liver disease, focusing on current treatment options and future perspectives.
Collapse
Affiliation(s)
- Milos Brankovic
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
- Transatlantic Cardiovascular Study Group, Bloomfield, NJ, USA
| | - Paul Lee
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Mark Klapholz
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
- Division of Cardiology, Heart Failure Prevention and Treatment Program, Rutgers New Jersey Medical School, Newark, NJ, USA
| |
Collapse
|
|
15
|
Jose A, Elwing JM, Kawut SM, Pauciulo MW, Sherman KE, Nichols WC, Fallon MB, McCormack FX. Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension. Commun Biol 2023; 6:826. [PMID: 37558836 PMCID: PMC10412637 DOI: 10.1038/s42003-023-05193-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 07/31/2023] [Indexed: 08/11/2023] Open
Abstract
Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease due to portal hypertension that exhibits high morbidity and mortality. The mechanisms driving disease are unknown, and transcriptional characteristics unique to the PoPH liver remain unexplored. Here, we apply single nuclear RNA sequencing to compare cirrhotic livers from patients with and without PoPH. We identify characteristics unique to PoPH in cells surrounding the central hepatic vein, including increased growth differentiation factor signaling, enrichment of the arginine biosynthesis pathway, and differential expression of the bone morphogenic protein type II receptor and estrogen receptor type I genes. These results provide insight into the transcriptomic characteristics of the PoPH liver and mechanisms by which PoPH cellular dysfunction might contribute to pulmonary vascular remodeling.
Collapse
Affiliation(s)
- Arun Jose
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
| | - Jean M Elwing
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Steven M Kawut
- Department of Medicine, Perelman School at the University of Pennsylvania, Philadelphia, PA, USA
| | - Michael W Pauciulo
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Kenneth E Sherman
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - William C Nichols
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | | | - Francis X McCormack
- Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| |
Collapse
|
|
16
|
Wakabayashi S, Joshita S, Kimura K, Motoki H, Okumura T, Kobayashi H, Yamashita Y, Sugiura A, Yamazaki T, Kimura T, Kuwahara K, Umemura T. Symptom-based portopulmonary hypertension screening questionnaire in Japanese patients with chronic liver disease. JGH Open 2023; 7:527-536. [PMID: 37649859 PMCID: PMC10463024 DOI: 10.1002/jgh3.12939] [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: 03/24/2023] [Revised: 06/21/2023] [Accepted: 06/29/2023] [Indexed: 09/01/2023]
Abstract
Background and Aim As the exact prevalence of portopulmonary hypertension (PoPH) and the etiology of chronic liver disease (CLD) remain unknown, the present study aimed to clarify these points in Japanese patients with CLD using symptom-based questionnaire screening. Methods Patients with CLD were asked to complete an eight-item written questionnaire on pulmonary hypertension (PH) symptoms. If at least one item response was "yes," the patient was offered ultrasonic echocardiography (UCG). Patients identified as having an intermediate or high risk of PH by UCG were referred to a cardiologist for further evaluation, whereby a definitive diagnosis of PoPH was made using right heart catheterization (RHC) findings. Results A total of 1111 patients with CLD completed the survey. Of the 566 symptomatic patients with at least one question answered as "yes," approximately half agreed to undergo UCG (n = 267). Compared with asymptomatic patients, symptomatic patients were significantly older, predominantly female, and more frequently exhibited cirrhosis. Based on UCG findings, 228, 12, and 8 patients had a low, intermediate, or high risk for PH, respectively. Intermediate-/high-risk patients showed significantly more advanced disease progression status than low-risk patients. The frequencies of answer to the eight questions were comparable. Ultimately, three patients were diagnosed as having PoPH (1.1% of UCG cases), one with underlying hepatitis C virus (HCV) infection and two with primary biliary cholangitis (PBC). Conclusion This symptom-based PoPH screening study clarified the prevalence of PoPH in CLD patients according to a PH symptom questionnaire, UCG, and RHC. Patients with HCV and PBC may have a higher risk of PoPH.
Collapse
Affiliation(s)
- Shun‐Ichi Wakabayashi
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
| | - Satoru Joshita
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
- Department of Health Promotion MedicineShinshu University School of MedicineMatsumotoJapan
| | - Kazuhiro Kimura
- Department of Cardiovascular MedicineShinshu University School of MedicineMatsumotoJapan
| | - Hirohiko Motoki
- Department of Cardiovascular MedicineShinshu University School of MedicineMatsumotoJapan
| | - Taiki Okumura
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
| | - Hiroyuki Kobayashi
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
- Department of Health Promotion MedicineShinshu University School of MedicineMatsumotoJapan
| | - Yuki Yamashita
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
- Department of Advanced Endoscopic TherapyShinshu University School of MedicineMatsumotoJapan
| | - Ayumi Sugiura
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
| | - Tomoo Yamazaki
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
| | - Takefumi Kimura
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
- Consultation Center for Liver DiseasesShinshu University HospitalMatsumotoJapan
| | - Koichiro Kuwahara
- Department of Cardiovascular MedicineShinshu University School of MedicineMatsumotoJapan
| | - Takeji Umemura
- Department of Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
- Department of Health Promotion MedicineShinshu University School of MedicineMatsumotoJapan
- Department of Advanced Endoscopic TherapyShinshu University School of MedicineMatsumotoJapan
- Consultation Center for Liver DiseasesShinshu University HospitalMatsumotoJapan
| |
Collapse
|
|
17
|
Jasso-Baltazar EA, Peña-Arellano GA, Aguirre-Valadez J, Ruiz I, Papacristofilou-Riebeling B, Jimenez JV, García-Carrera CJ, Rivera-López FE, Rodriguez-Andoney J, Lima-Lopez FC, Hernández-Oropeza JL, Díaz JAT, Kauffman-Ortega E, Ruiz-Manriquez J, Hernández-Reyes P, Zamudio-Bautista J, Rodriguez-Osorio CA, Pulido T, Muñoz-Martínez S, García-Juárez I. Portopulmonary Hypertension: An Updated Review. Transplant Direct 2023; 9:e1517. [PMID: 37492078 PMCID: PMC10365198 DOI: 10.1097/txd.0000000000001517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 05/30/2023] [Accepted: 06/01/2023] [Indexed: 07/27/2023] Open
Abstract
Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.
Collapse
Affiliation(s)
- Erick A. Jasso-Baltazar
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Gonzalo A. Peña-Arellano
- Department of Gastroenterology, Instituto de Seguridad Social del Estado de México y Municipios, Mexico State, Mexico
| | | | - Isaac Ruiz
- Departament of Hepatology and Liver Trasplantation, Centre Hospitalier de I´Universite of Montréal, Montreal, Canada
| | - Bruno Papacristofilou-Riebeling
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jose Victor Jimenez
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Cristian J. García-Carrera
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Fabián E. Rivera-López
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesús Rodriguez-Andoney
- Pulmonary Circulation Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Francisco C. Lima-Lopez
- Cardiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José Luis Hernández-Oropeza
- Pulmonary Circulation Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Juan A. Torres Díaz
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eric Kauffman-Ortega
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesus Ruiz-Manriquez
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Pablo Hernández-Reyes
- Cardiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jorge Zamudio-Bautista
- Department of Anesthesiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carlos A. Rodriguez-Osorio
- Department of Critical Care Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Tomás Pulido
- Cardiopulmonary Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| |
Collapse
|
|
18
|
Kondo T, Fujiwara K, Nakagawa M, Fujimoto K, Yumita S, Ishino T, Ogawa K, Iwanaga T, Koroki K, Kanzaki H, Inoue M, Kobayashi K, Kiyono S, Nakamura M, Kanogawa N, Ogasawara S, Nakamoto S, Chiba T, Kato J, Kato N. Estimation of the effect of atezolizumab plus bevacizumab on pulmonary arterial hypertension using computed tomography in HCC patients. Sci Rep 2023; 13:11524. [PMID: 37460776 DOI: 10.1038/s41598-023-38377-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/07/2023] [Indexed: 07/20/2023] Open
Abstract
The effect of the combination of atezolizumab and bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC) on pulmonary arterial hypertension (PAH) is unknown. Estimation of PAH by using computed tomography (CT) has recently been proposed. Thus, we aimed to estimate the effect of Atez/Bev on PAH using CT. Altogether, 113 patients who received Atez/Bev for HCC were enrolled. Probable PAH was defined as the diameter of the main pulmonary artery (mPA-D) ≥ 33 mm, whereas suspicious PAH was defined as mPA-D ≥ 29 mm or mPA-D/the diameter of the ascending aorta (aAo-D) ≥ 1.0. Before treatment, probable/suspicious PAH were diagnosed in 7 (6.7%)/22 (21.0%) patients, respectively. mPA-D and mPA-D/aAo-D significantly increased after induction of Atez/Bev. The increment of mPA-D was correlated with the occurrence of post-treatment respiratory/heart failure. In analysis of 55 patients who underwent CT at 3 months after the last dose of Atez/Bev, mPA-D and mPA-D/aAo-D significantly decreased. However, in the group with continuous treatment of other molecular-targeted drugs after Atez/Bev, mPA-D and mPA-D/aAo-D showed no significant change. In conclusion, PAH may not be a rare complication in patients with HCC and should be managed carefully because of the possible negative effect of Atez/Bev on PAH.
Collapse
Affiliation(s)
- Takayuki Kondo
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan.
- Ultrasound Center, Chiba University Hospital, Chiba, Japan.
| | - Kisako Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Miyuki Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Kentaro Fujimoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Sae Yumita
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Takamasa Ishino
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Keita Ogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Terunao Iwanaga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Keisuke Koroki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Hiroaki Kanzaki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Masanori Inoue
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Jun Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan
- Ultrasound Center, Chiba University Hospital, Chiba, Japan
| |
Collapse
|
|
19
|
Miwa T, Hanai T, Nishimura K, Tajirika S, Nakahata Y, Imai K, Suetsugu A, Takai K, Yamamoto M, Shimizu M. Association between Body Composition and the Risk of Portopulmonary Hypertension Assessed by Computed Tomography in Patients with Liver Cirrhosis. J Clin Med 2023; 12:3351. [PMID: 37240457 PMCID: PMC10219301 DOI: 10.3390/jcm12103351] [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: 03/04/2023] [Revised: 04/24/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
The aim of this study is to investigate the impact of body composition on the risk of portopulmonary hypertension using computed tomography (CT) in patients with liver cirrhosis. We retrospectively included 148 patients with cirrhosis treated at our hospital between March 2012 and December 2020. POPH high-risk was defined as main pulmonary artery diameter (mPA-D) ≥ 29 mm or mPA-D to ascending aorta diameter ratio ≥ 1.0, based on chest CT. Body composition was assessed using CT images of the third lumbar vertebra. The factors associated with POPH high-risk were evaluated using logistic regression and decision tree analyses, respectively. Among the 148 patients, 50% were females, and 31% were found to be high-risk cases on evaluation of chest CT images. Patients with a body mass index (BMI) of ≥25 mg/m2 had a significantly higher prevalence of POPH high-risk than those with a BMI < 25 mg/m2 (47% vs. 25%, p = 0.019). After adjusting for confounding factors, BMI (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.10-1.33), subcutaneous adipose tissue index (OR, 1.02; 95% CI, 1.01-1.03), and visceral adipose tissue index (OR, 1.03; 95% CI, 1.01-1.04) were associated with POPH high-risk, respectively. In the decision tree analysis, the strongest classifier of POPH high-risk was BMI, followed by the skeletal muscle index. Body composition may affect the risk of POPH based on chest CT assessment in patients with cirrhosis. Since the present study lacked data on right heart catheterization, further studies are required to confirm the results of our study.
Collapse
Affiliation(s)
- Takao Miwa
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
- Health Administration Center, Gifu University, Gifu 501-1193, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu 501-1194, Japan
| | - Kayoko Nishimura
- Center for Nutrition Support & Infection Control, Gifu University Hospital, Gifu 501-1194, Japan
| | - Satoko Tajirika
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
- Health Administration Center, Gifu University, Gifu 501-1193, Japan
| | - Yuki Nakahata
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
- Department of Gastroenterology, Asahi University Hospital, Gifu 501-1194, Japan
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
- Division for Regional Cancer Control, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
| | - Mayumi Yamamoto
- Health Administration Center, Gifu University, Gifu 501-1193, Japan
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
| |
Collapse
|
|
20
|
Tamura Y, Tamura Y, Taniguchi Y, Atsukawa M. Current clinical understanding and effectiveness of portopulmonary hypertension treatment. Front Med (Lausanne) 2023; 10:1142836. [PMID: 37081835 PMCID: PMC10110923 DOI: 10.3389/fmed.2023.1142836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 02/28/2023] [Indexed: 04/07/2023] Open
Abstract
Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic.
Collapse
Affiliation(s)
- Yuichi Tamura
- Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan
- Department of Cardiology, International University of Health and Welfare School of Medicine, Narita, Japan
- *Correspondence: Yuichi Tamura,
| | - Yudai Tamura
- Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan
- Department of Cardiology, International University of Health and Welfare School of Medicine, Narita, Japan
| | - Yu Taniguchi
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| |
Collapse
|
|
21
|
Jose A, Kopras EJ, Shah SA, Elwing JM. Portopulmonary hypertension practice patterns after liver transplantation. Liver Transpl 2023; 29:365-376. [PMID: 36117426 PMCID: PMC9985659 DOI: 10.1002/lt.26575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/31/2022] [Accepted: 09/08/2022] [Indexed: 12/14/2022]
Abstract
Portopulmonary hypertension (POPH) is a type of pulmonary arterial hypertension occurring exclusively in those with portal hypertensive liver disease. Liver transplantation (LT) can significantly improve outcomes. Current guidelines counsel against immediate adjustments to targeted therapy after LT and suggest routine echocardiography as sufficiently informative to guide therapeutic adjustments. Current practice patterns for adjusting targeted therapy after LT in POPH, and how they compare with guidelines, are not well established. To answer this question, we performed an institutional review board-approved, cross-sectional mixed-methods survey-based study of US POPH providers. Anonymized requests to complete the survey were sent through professional networks between January 20, 2022, and April 20, 2022. Responses were compared between cardiologists and pulmonologists using Fisher's exact tests, at a significance of 0.05. A total of 85 POPH physicians were included in the final analysis (66% pulmonologists and 34% cardiologists). Following LT, the majority of respondents routinely used a combination of standard cardiopulmonary assessment modalities to guide adjustment of targeted therapy following LT. Most respondents (69%) started by adjusting parenteral prostacyclins with small titrations and frequent reassessments within 3 months of LT, but some (19.7%) adjusted targeted therapy immediately after LT. Our results showed that the majority of respondents favored serial integrated cardiopulmonary testing (including routine right heart catheterization) to guide the adjustment of targeted therapy in POPH after LT, and almost one-fifth of respondents weaned therapy immediately after LT. Our study demonstrates heterogeneity in POPH practice patterns after LT, highlights differences between current practice patterns and the most recent guidelines, emphasizes the need for additional research, and supports a team-based approach to standardize care for these high-risk patients and optimize post-LT outcomes.
Collapse
Affiliation(s)
- Arun Jose
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH
| | - Elizabeth J. Kopras
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH
| | - Shimul A. Shah
- Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Jean M. Elwing
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH
| |
Collapse
|
|
22
|
Sodhi A, Cox-Flaherty K, Greer MK, Lat TI, Gao Y, Polineni D, Pisani MA, Bourjeily G, Glassberg MK, D'Ambrosio C. Sex and Gender in Lung Diseases and Sleep Disorders: A State-of-the-Art Review: Part 2. Chest 2023; 163:366-382. [PMID: 36183784 PMCID: PMC10083131 DOI: 10.1016/j.chest.2022.08.2240] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/30/2022] [Accepted: 08/31/2022] [Indexed: 01/14/2023] Open
Abstract
There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder.
Collapse
Affiliation(s)
- Amik Sodhi
- Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin, Madison, WI
| | - Katherine Cox-Flaherty
- Division of Pulmonary, Critical Care and Sleep Medicine, Brown University, Providence, RI
| | - Meredith Kendall Greer
- Division of Pulmonary, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, GA
| | - Tasnim I Lat
- Division of Pulmonary, Critical Care and Sleep Medicine, Baylor Scott & White Health, Temple, TX
| | - Yuqing Gao
- Division of Pulmonary, Critical Care and Sleep Medicine, University of Arizona College of Medicine Phoenix, Phoenix, AZ
| | - Deepika Polineni
- Division of Pulmonary, Critical Care and Sleep Medicine, Washington University at St. Louis, St. Louis, MO
| | - Margaret A Pisani
- Division of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT
| | - Ghada Bourjeily
- Division of Pulmonary, Critical Care and Sleep Medicine, Brown University, Providence, RI
| | - Marilyn K Glassberg
- Division of Pulmonary, Critical Care and Sleep Medicine, University of Arizona College of Medicine Phoenix, Phoenix, AZ
| | - Carolyn D'Ambrosio
- Division of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT.
| |
Collapse
|
|
23
|
Atsukawa M, Tsubota A, Kondo C, Koyano KS, Ishikawa T, Toyoda H, Takaguchi K, Watanabe T, Matsuura K, Ogawa C, Hiraoka A, Okubo H, Tateyama M, Uojima H, Nozaki A, Chuma M, Kato K, Mikami S, Tani J, Morishita A, Kawata K, Tada T, Furuichi Y, Okubo T, Kawano T, Arai T, Kawabe N, Kawamura N, Ikegami T, Nakamuta M, Shigefuku R, Iwasa M, Tanaka Y, Hatano M, Iwakiri K. Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study. Hepatol Int 2023; 17:139-149. [PMID: 36477691 DOI: 10.1007/s12072-022-10456-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/12/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations. RESULTS A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score. CONCLUSIONS This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.
Collapse
Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan.
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| | - Kaori-Shioda Koyano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Masakuni Tateyama
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Shigeru Mikami
- Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Hygo, Japan
| | - Yoshihiro Furuichi
- Department of Clinical Laboratory and Endoscopy, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| | - Naoto Kawabe
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Aichi, Japan
| | - Naohiro Kawamura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Tadashi Ikegami
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
| | - Makoto Nakamuta
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Ryuta Shigefuku
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaru Hatano
- Department of Advanced Medical Center for Heart Failure, The University of Tokyo Hospital, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| |
Collapse
|
|
24
|
Lai YK, Kwo PY. Portopulmonary Hypertension. Clin Liver Dis 2023; 27:71-84. [PMID: 36400468 DOI: 10.1016/j.cld.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
PoPH is a well-recognized complication of portal hypertension with or without cirrhosis and is classified as a subset of PAH. Identification of PoPH is crucial as it has a major impact on prognosis and liver transplant candidacy. Echocardiogram is the initial screening tool of choice and the patient should proceed to RHC for confirmation. PAH-directed therapy is the treatment of choice, allowing the patient to achieve a hemodynamic threshold to undergo a liver transplant safely.
Collapse
Affiliation(s)
- Yu Kuang Lai
- Pulmonary, Allergy and Critical Care, Department of Medicine, Stanford University, 300 Pasteur Drive, Room H3143, Palo Alto, CA 94304, USA
| | - Paul Y Kwo
- Stanford University School of Medicine, 430 Broadway, Pavilion C, 3rd Floor, Redwood City, CA 94063, USA.
| |
Collapse
|
|
25
|
Portopulmonary Hypertension: Management and Liver Transplantation Evaluation. Chest 2023:S0012-3692(23)00043-0. [PMID: 36649754 DOI: 10.1016/j.chest.2023.01.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 01/06/2023] [Indexed: 01/15/2023] Open
Abstract
Portopulmonary hypertension (POPH) affects 5% to 6% of patients with advanced liver disease and accounts for 5% to 15% of pulmonary arterial hypertension (PAH) cases. Compared with idiopathic PAH, POPH is associated with significantly worse survival. Recent studies have improved our understanding of the role of both PAH therapy and liver transplantation (LT) in the management of POPH and their impact on overall prognosis. We performed a review of the published literature to summarize the available evidence and guidelines regarding the diagnosis and management of POPH. POPH is defined by the presence of precapillary PH in the context of portal hypertension. POPH is associated with increased perioperative risk at the time of LT, which can be stratified by mean pulmonary arterial pressure and pulmonary vascular resistance. Screening with echocardiography is recommended in all LT candidates to facilitate detection and treatment of POPH. Despite a paucity of evidence, POPH is treated similarly to idiopathic PAH with PAH therapy. These therapies are associated with improved pulmonary hemodynamics and facilitation of safe LT. LT can result in improvement or resolution of POPH in half of patients and has been associated with improved survival in highly selected patients. The prognosis in POPH is poor and is impacted by the severity of both PH and liver disease. Management with a combination of PAH therapy and LT in selected patients has been associated with improved pulmonary hemodynamics and survival.
Collapse
|
|
26
|
Tokushige K, Kogiso T, Egawa H. Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan. J Clin Med 2023; 12:jcm12020562. [PMID: 36675490 PMCID: PMC9867251 DOI: 10.3390/jcm12020562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/23/2022] [Accepted: 01/07/2023] [Indexed: 01/12/2023] Open
Abstract
Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure <35 mmHg and pulmonary vascular resistance <400 dyn/s/cm−5 are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT.
Collapse
Affiliation(s)
- Katsutoshi Tokushige
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
- Correspondence: ; Tel.: +81-3-3353-8111; Fax: +81-3-5269-7507
| | - Tomomi Kogiso
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Hiroto Egawa
- Department of Hepatopancreatic Surgery, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| |
Collapse
|
|
27
|
Gera A, Pant D. Preoperative Assessment and Optimization of Liver Transplant Patients: Pulmonary Issues. PERI-OPERATIVE ANESTHETIC MANAGEMENT IN LIVER TRANSPLANTATION 2023:147-161. [DOI: 10.1007/978-981-19-6045-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
28
|
Abstract
Portopulmonary hypertension (PoPH) is a progressive, ultimately fatal cardiopulmonary disease that occurs exclusively in patients with underlying portal hypertensive liver disease. PoPH outcomes are driven by both the severity of underlying liver disease and the degree of cardiac adaptation to elevated pulmonary pressures. The mainstay of treatment in PoPH is targeted pulmonary vascular therapy. Liver transplantation (LT) can be beneficial in some patients, but is associated with considerable risks in the PoPH population, and outcomes are variable. The optimal management strategy for PoPH, LT, or medical therapy alone, is unclear, and further research is needed to help guide clinical decision-making.
Collapse
Affiliation(s)
- Arun Jose
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, ML 0564, Medical Sciences Building, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
| | - Courtney R Jones
- Department of Anesthesiology, University of Cincinnati, ML 3553, Medical Sciences Building, 231 Albert Sabin Way, Cincinnati, OH 45267, USA
| | - Jean M Elwing
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, ML 0564, Medical Sciences Building, 231 Albert Sabin Way, Cincinnati, OH 45267, USA
| |
Collapse
|
|
29
|
Temporal Trends in Portopulmonary Hypertension Model for End-stage Liver Disease Exceptions and Outcomes. Transplant Direct 2022; 8:e1410. [PMID: 36398194 PMCID: PMC9666225 DOI: 10.1097/txd.0000000000001410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 09/06/2022] [Accepted: 10/03/2022] [Indexed: 11/16/2022] Open
Abstract
Model for end-stage liver disease (MELD) exception criteria for portopulmonary hypertension (POPH) were created to prioritize patients for liver transplant before POPH progression. Little is known about trends in POPH exception frequency, disease severity, pulmonary hypertension treatment patterns, or outcomes since the POPH MELD exception began.
Collapse
|
|
30
|
Atsukawa M, Takano M, Omura J. Treatment pattern and clinical outcomes in portopulmonary hypertension: A database study in Japan. JGH OPEN 2022; 6:763-773. [DOI: 10.1002/jgh3.12820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 08/17/2022] [Accepted: 09/04/2022] [Indexed: 11/07/2022]
Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan
| | - Masashi Takano
- Medical Affairs Division Janssen Pharmaceutical K.K. Tokyo Japan
| | - Junichi Omura
- Medical Affairs Division Janssen Pharmaceutical K.K. Tokyo Japan
| |
Collapse
|
|
31
|
Douschan P, Kovacs G, Sassmann T, Stadlbauer V, Avian A, Foris V, Tatscher E, Durchschein F, Rainer F, Spindelboeck W, Wagner M, Kniepeiss D, Zollner G, Bachmaier G, Fickert P, Olschewski H, Stauber RE. Pulmonary vascular disease and exercise hemodynamics in chronic liver disease. Respir Med 2022; 202:106987. [PMID: 36115317 DOI: 10.1016/j.rmed.2022.106987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/27/2022] [Accepted: 09/06/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND & AIMS Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. METHODS We assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21-24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. RESULTS Two-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50-60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. CONCLUSION In chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.
Collapse
Affiliation(s)
- Philipp Douschan
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Gabor Kovacs
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
| | - Teresa Sassmann
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Vanessa Stadlbauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Alexander Avian
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Vasile Foris
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Elisabeth Tatscher
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Franziska Durchschein
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Walter Spindelboeck
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Martin Wagner
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Daniela Kniepeiss
- Department of General, Visceral and Transplant Surgery, Transplant Center Graz, Medical University of Graz, Graz, Austria
| | - Gernot Zollner
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Gerhard Bachmaier
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Peter Fickert
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Horst Olschewski
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Rudolf E Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| |
Collapse
|
|
32
|
Yamashita K, Kurosaki M, Nakanishi H, Tanaka Y, Ishido S, Inada K, Kirino S, Hayakawa Y, Matsumoto H, Nobusawa T, Kakegawa T, Higuchi M, Takaura K, Tanaka S, Maeyashiki C, Kaneko S, Tamaki N, Yasui Y, Tsuchiya K, Takahashi Y, Miyazaki R, Ashikaga T, Enomoto N, Izumi N. Simple algorithm to narrow down the candidates to receive echocardiography in patients with chronic liver disease for suspected pulmonary hypertension. JGH Open 2022; 6:774-781. [PMID: 36406650 PMCID: PMC9667407 DOI: 10.1002/jgh3.12821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 08/09/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022]
Abstract
Aims Portopulmonary hypertension (PoPH) is a subtype of pulmonary arterial hypertension related to portal hypertension. The definitive diagnosis of PoPH is made by invasive right heart catheterization. Alternatively, pulmonary arterial hypertension may be recognized noninvasively from the tricuspid regurgitant pressure gradient (TRPG), measured by echocardiography. In this study, we aimed to establish a simple algorithm to identify chronic liver disease patients with a high TRPG value in order to narrow down the candidates to receive echocardiography. Methods and Results TRPG was measured by echocardiography in 152 patients with chronic liver disease. Factors predictive of TRPG >30 mmHg were investigated. There were 28 (18%) cases with TRPG >30 mmHg. Independent factors associated with a high TRPG were the presence of shortness of breath, high serum brain natriuretic peptide (BNP), and low serum albumin. Child–Pugh class or the presence of ascites, varices, or encephalopathy was not associated with TRPG. There was a correlation between the serum BNP and TRPG, and the optimal cutoff value of BNP by the Youden index was 122 pg/mL, and by 100% sensitivity was 50 pg/mL. A combination of these factors identified patients with a high probability of TRPG >30 mmHg (n = 12, positive predictive value [PPV] of 83%), no probability (n = 80, PPV 0%), and intermediate probability (n = 60, PPV 25–34%). This algorithm has reduced the number of patients needing echocardiography by 53%. Conclusions A simple algorithm using the presence of shortness of breath, serum BNP, and albumin levels can narrow down the candidates to receive echocardiography.
Collapse
Affiliation(s)
- Koji Yamashita
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
- First Department of Internal Medicine, Faculty of Medicine University of Yamanashi Yamanashi Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yuki Tanaka
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Shun Ishido
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Hiroaki Matsumoto
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Tsubasa Nobusawa
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Tatsuya Kakegawa
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Shohei Tanaka
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Ryoichi Miyazaki
- Department of Cardiology Musashino Red Cross Hospital Tokyo Japan
| | - Takashi Ashikaga
- Department of Cardiology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine University of Yamanashi Yamanashi Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| |
Collapse
|
|
33
|
Mehra P, Mehta V, Yusuf J, Mukhopadhyay S, Dabla PK, Parashar L, Sukhija R, Aronow WS. Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease. Indian Heart J 2022; 74:375-381. [PMID: 36179900 PMCID: PMC9647693 DOI: 10.1016/j.ihj.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 09/08/2022] [Accepted: 09/25/2022] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. AIM We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). METHODS We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. RESULTS The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females. CONCLUSIONS ET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.
Collapse
Affiliation(s)
- Pratishtha Mehra
- Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Vimal Mehta
- Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
| | - Jamal Yusuf
- Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Saibal Mukhopadhyay
- Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Pradeep Kumar Dabla
- Department of Biochemistry, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Lokesh Parashar
- Statistician, ESIC Medical College and Hospital, Faridabad, India
| | - Rishi Sukhija
- Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| |
Collapse
|
|
34
|
DuBrock HM, Del Valle KT, Krowka MJ. Mending the Model for End-Stage Liver Disease: An in-depth review of the past, present, and future portopulmonary hypertension Model for End-Stage Liver Disease exception. Liver Transpl 2022; 28:1224-1230. [PMID: 35106916 DOI: 10.1002/lt.26422] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/10/2022] [Accepted: 01/25/2022] [Indexed: 02/06/2023]
Abstract
Patients with portopulmonary hypertension (POPH) have an increased cardiovascular and overall mortality risk when undergoing liver transplantation (LT). However, such risk is not captured in their Model for End-Stage Liver Disease (MELD) laboratory score. POPH MELD exception criteria were established in 2006 with the aim of prioritizing these patients for LT prior to pulmonary hypertension (PH) progression and eventual right heart failure. The original criteria emphasized a posttreatment, pre-LT mean pulmonary arterial pressure (mPAP) of <35 mm Hg and pulmonary vascular resistance (PVR) <400 dynes-s-cm-5 or <5 Wood units (WU). Since 2006, there have been important advances in the treatment of POPH with pulmonary arterial hypertension (PAH)-targeted therapies and newer evidence regarding LT outcomes and risk factors for perioperative mortality. Specifically, PVR rather than mPAP has been shown to be more strongly associated with outcomes, including mortality. In addition, among treated patients with POPH, mPAP may be persistently elevated related to an elevated cardiac output or other factors that do not necessarily reflect POPH disease severity. Thus, in February 2021, the Organ Procurement and Transplantation Network approved proposed modifications to POPH MELD exception criteria, now allowing either of the following posttreatment, pre-LT hemodynamic profiles: mPAP less than 35 mm Hg and posttreatment PVR less than 400 dynes-s-cm-5 (or less than 5 WU) or mPAP greater than or equal to 35 mm Hg and less than 45 mm Hg and posttreatment PVR less than 240 dynes-s-cm-5 (or less than 3 WU). This article reviews the history of the POPH MELD exception criteria, describes the recent modifications to the exception criteria and the evidence supporting them, and highlights unanswered questions and areas for future research.
Collapse
Affiliation(s)
- Hilary M DuBrock
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Kathryn T Del Valle
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
35
|
Peppas S, Nagraj S, Koutsias G, Kladas M, Archontakis-Barakakis P, Schizas D, Giannakoulas G, Palaiodimos L, Kokkinidis DG. Portopulmonary Hypertension: A Review of the Current Literature. Heart Lung Circ 2022; 31:1191-1202. [PMID: 35667970 DOI: 10.1016/j.hlc.2022.04.056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 04/05/2022] [Accepted: 04/21/2022] [Indexed: 12/20/2022]
Abstract
Portopulmonary hypertension is defined as the development of pulmonary arterial hypertension in the setting of portal hypertension with or without liver cirrhosis. Portal hypertension-associated haemodynamic changes, including hyperdynamic state, portosystemic shunts and splanchnic vasodilation, induce significant alterations in pulmonary vascular bed and play a pivotal role in the pathogenesis of the disease. If left untreated, portopulmonary hypertension results in progressive right heart failure, with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and liver transplantation candidates, right heart catheterisation remains the gold standard for the diagnosis of the disease. Severe portopulmonary hypertension exerts a prohibitive risk to liver transplantation by conferring an elevated perioperative mortality risk. It is important for haemodynamic parameters to correspond with non-severe portopulmonary hypertension before patients can proceed with the liver transplantation. Small uncontrolled studies and a recent randomised controlled trial have reported promising results with vasodilatory therapies in clinical and haemodynamic improvement of patients, allowing a proportion of patients to undergo liver transplantation. In this review, the epidemiology, pathogenesis, diagnostic approach and management of portopulmonary hypertension are discussed. We also highlight fields of ongoing investigation pertinent to risk stratification and optimal patient selection to maximise long-term benefit from currently available treatments.
Collapse
Affiliation(s)
- Spyros Peppas
- Department of Gastroenterology, Athens Naval Hospital, Athens, Greece.
| | - Sanjana Nagraj
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA; Division of Hospital Medicine, Jacobi Medical Center, Bronx, NY, USA
| | - George Koutsias
- Aristotle University of Thessaloniki, Division of Vascular Surgery, 2(nd) Department of Surgery, Thessaloniki, Greece
| | - Michail Kladas
- Internal Medicine, North Central Bronx Hospital and James J. Peters VA Medical Center, Bronx, NY, USA
| | | | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - George Giannakoulas
- Department of Cardiology, AHEPA University Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Leonidas Palaiodimos
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA; Division of Hospital Medicine, Jacobi Medical Center, Bronx, NY, USA
| | - Damianos G Kokkinidis
- Section of Cardiovascular Medicine, Yale University/Yale New Haven Hospital, New Haven, CT, USA
| |
Collapse
|
|
36
|
Gupta A, Pradhan A, Mehrotra S, Misra R, Usman K, Kumar A, Pandey S. Prevalence and Clinical Features of Portopulmonary Hypertension in Patients With Hepatic Cirrhosis: An Echocardiographic Study. Cureus 2022; 14:e24957. [PMID: 35698719 PMCID: PMC9188673 DOI: 10.7759/cureus.24957] [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] [Accepted: 04/26/2022] [Indexed: 02/05/2023] Open
Abstract
Objective The present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored. Methods A prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared. Results The prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension (5.50±0.68 g/dl vs. 7.26±1.43 g/dl, p=0.001). All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular (basal, p=0.0001; longitudinal, p=0.0001) dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter (major: p=0.0001; right: p=0.0001; and left: p=0.007), pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Conclusions The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension.
Collapse
Affiliation(s)
- Anany Gupta
- Medicine, King George's Medical University, Lucknow, IND
| | | | | | - Ravi Misra
- Medicine, King George's Medical University, Lucknow, IND
| | - Kauser Usman
- Medicine, King George's Medical University, Lucknow, IND
| | - Ajay Kumar
- Medicine, King George's Medical University, Lucknow, IND
| | - Shivani Pandey
- Biochemistry, King George's Medical University, Lucknow, IND
| |
Collapse
|
|
37
|
Ryan A, Miah N, Saleh M. Portopulmonary hypertension: a patient with shortness of breath. BMJ Case Rep 2022; 15:e244803. [PMID: 35473699 PMCID: PMC9045005 DOI: 10.1136/bcr-2021-244803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2021] [Indexed: 11/03/2022] Open
Abstract
Portopulmonary hypertension (PoPH) is a poorly understood complication of liver disease which affects about 10% of patients with pulmonary hypertension. This case report outlines the difficulties in diagnosing and managing a patient with advanced disease, and the impact of these delays on the patient.PoPH has a significant risk of mortality with a 2-year survival rate of 67%. There are also few treatment options available and those which do exist are associated with multiple contraindications and risks. Patients with PoPH commonly present with dyspnoea, pulmonary hypertension and portal hypertension. The presence of coexisting chronic liver disease is also sometimes present. Traditional management for heart failure can temporarily alleviate symptoms but there is no proven long-term benefit. As a result, an understanding of the pathophysiology, diagnostics and management is crucial to ensure the best possible patient outcomes.
Collapse
Affiliation(s)
- Aidan Ryan
- Medway Maritime Hospital, Gillingham, Kent, UK
| | - Nahima Miah
- Medway Maritime Hospital, Gillingham, Kent, UK
| | - Mohamed Saleh
- Gastroenterology, Medway Maritime Hospital, Gillingham, Kent, UK
| |
Collapse
|
|
38
|
Han S, Park J, Hong SH, Park CS, Choi J, Chae MS. Cardiovascular manifestation of end-stage liver disease and perioperative echocardiography for liver transplantation: anesthesiologist’s view. Anesth Pain Med (Seoul) 2022; 17:132-144. [PMID: 35538654 PMCID: PMC9091670 DOI: 10.17085/apm.22132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 03/30/2022] [Indexed: 11/19/2022] Open
Abstract
Liver transplantation (LT) is the curative therapy for decompensated cirrhosis. However, anesthesiologists can find it challenging to manage patients undergoing LT due to the underlying pathologic conditions of patients with end-stage liver disease and the high invasiveness of the procedure, which is frequently accompanied by massive blood loss. Echocardiography is a non-invasive or semi-invasive imaging tool that provides real-time information about the structural and functional status of the heart and is considered to be able to improve outcomes by enabling accurate and detailed assessments. This article reviews the pathophysiologic changes of the heart accompanied by cirrhosis that mainly affect hemodynamics. We also present a comparative review of the diagnostic criteria for cirrhotic cardiomyopathy published by the World Congress of Gastroenterology in 2005 and the Cirrhotic Cardiomyopathy Consortium in 2019. This article discusses the conditions that could affect hemodynamic stability and postoperative outcomes, such as coronary artery disease, left ventricular outflow tract obstruction, portopulmonary hypertension, hepatopulmonary syndrome, pericardial effusion, cardiac tamponade, patent foramen ovale, and ascites. Finally, we cover a number of intraoperative factors that should be considered, including intraoperative blood loss, rapid reaccumulation of ascites, manipulation of the inferior vena cava, post-reperfusion syndrome, and adverse effects of excessive fluid infusion and transfusion. This article aimed to summarize the cardiovascular manifestations of cirrhosis that can affect hemodynamics and can be evaluated using perioperative echocardiography. We hope that this article will provide information about the hemodynamic characteristics of LT recipients and stimulate more active use of perioperative echocardiography.
Collapse
Affiliation(s)
- Sangbin Han
- Department of Emergency Medicine, Cheongyang Health Center County Hospital, Cheongyang, Korea
| | - Jaesik Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang Hyun Hong
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Soo Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jongho Choi
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min Suk Chae
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Corresponding author Min Suk Chae, M.D., Ph.D. Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: 82-2-2258-6150 Fax: 82-2-537-1951 E-mail:
| |
Collapse
|
|
39
|
Hayashi R, Kogiso T, Kikuchi N, Yamamoto K, Nakamura S, Egawa H, Hagiwara N, Tokushige K. Portopulmonary hypertension and the risk of high right ventricular systolic pressure in liver transplant candidates. PLoS One 2022; 17:e0267125. [PMID: 35439259 PMCID: PMC9017876 DOI: 10.1371/journal.pone.0267125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 04/02/2022] [Indexed: 12/28/2022] Open
Abstract
Aim Portopulmonary hypertension (PoPH) is a rare and serious complication of liver cirrhosis and portal hypertension that can interfere with liver transplantation (LT). We evaluated the prevalence of PoPH and the clinical features of right ventricular systolic pressure (RVSP), which is equivalent to pulmonary artery systolic pressure, in LT candidates. Methods This was a single-center retrospective study. A total of 157 Japanese patients with decompensated liver cirrhosis or portal hypertension (76 men, median age = 52 years [range: 18–68 years]) were enrolled. The relationships between RVSP and clinical parameters, and the prevalence of PoPH in LT candidates, were evaluated. Results The cardiological parameters were as follows: brain natriuretic peptide (BNP), 39.1 (4.0–780.5) pg/mL; RVSP, 31.2 (16.0–122.4) mmHg; ejection fraction, 58% (28–72%); and mean peak tricuspid regurgitation velocity, 2.3 (1.5–5.3) m/s. The RVSP was significantly higher in females (p = 0.02) and primary biliary cholangitis (PBC) patients (p = 0.01), and was weakly correlated with the BNP level (r = 0.40, p = 0.01). For RVSPs of < 36 and ≥ 36 mmHg, the 5-year survival rates were 36.1% versus 34.1%, and 85.4% versus 85.3%, in non-LT and LT cases, respectively (p = 0.47 and 0.69, respectively). Among six patients with an RVSP ≥ 50 mmHg, three (1.9%) were diagnosed with PoPH and treated with vasodilators. Conclusions PoPH was observed in 3 cases (1.9%) in 157 LT candidates. In patients with suspected mild pulmonary hypertension (RVSP, 36 - 50 mmHg), LT was successfully performed.
Collapse
Affiliation(s)
- Ryoko Hayashi
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Tomomi Kogiso
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
- * E-mail:
| | - Noriko Kikuchi
- Department of Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Kana Yamamoto
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shinichi Nakamura
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Hiroto Egawa
- Department of surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Nobuhisa Hagiwara
- Department of Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| |
Collapse
|
|
40
|
Iwahashi N, Horii M, Tamura K, Kimura K. Worsening Dyspnea in Patients With Idiopathic Portal Hypertension. Chest 2022; 161:e245-e248. [DOI: 10.1016/j.chest.2021.05.077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/06/2021] [Accepted: 05/29/2021] [Indexed: 10/18/2022] Open
|
|
41
|
Ishikawa T, Egusa M, Kawamoto D, Nishimura T, Sasaki R, Saeki I, Sakaida I, Takami T. Screening for portopulmonary hypertension using computed tomography-based measurements of the main pulmonary artery and ascending aorta diameters in patients with portal hypertension. Hepatol Res 2022; 52:255-268. [PMID: 34822208 DOI: 10.1111/hepr.13735] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 11/10/2021] [Accepted: 11/23/2021] [Indexed: 12/12/2022]
Abstract
AIM This study aimed to demonstrate the feasibility of identifying candidates of portopulmonary hypertension (PoPH) from general portal hypertension patients based on chest computed tomography (CT) results. METHODS One hundred and thirty patients with portal hypertension who had undergone interventional radiology therapies at our hospital between August 2011 and July 2021 were included, and preoperative clinical data were collected. Suspicious PoPH was defined as main pulmonary artery diameter (mPA-D) ≥ 29 mm or the ratio of mPA-D to ascending aorta diameter (mPA-D/aAo-D) ≥ 1.0, and probable PoPH as mPA-D ≥ 33 mm based on the chest CT. Prevalence of suspicious and probable PoPH was evaluated, and the differences in clinical characteristics of each population were compared. RESULTS Overall, 29 (22.3%) and 5 (3.8%) patients were categorized as suspicious and probable PoPH, respectively. Univariate analyses revealed that female sex, higher shortest diameter of inferior vena cava, presence of portosystemic shunts ≥ 5 mm, and lower blood urea nitrogen levels were significantly associated with suspicious PoPH (p < 0.05). Multivariate analyses identified all four factors as significantly independent determinants of suspicious PoPH (p < 0.05). In addition, among the population of suspicious PoPH, there were significant differences in seven parameters, including total bilirubin levels and spleen volume between patients with and without probable PoPH (p < 0.05). However, no significant independent indicators of probable PoPH were found. CONCLUSIONS CT-based measurements of mPA-D and mPA-D/aAo-D have the potential to screen patients with suspicious PoPH in clinical practice focused on portal hypertension.
Collapse
Affiliation(s)
- Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Maho Egusa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Daiki Kawamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Tatsuro Nishimura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Ryo Sasaki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Issei Saeki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube-Yamaguchi, Japan
| |
Collapse
|
|
42
|
Xu H, Cheng B, Wang R, Ding M, Gao Y. Portopulmonary hypertension: Current developments and future perspectives. LIVER RESEARCH 2022; 6:10-20. [PMID: 39959808 PMCID: PMC11791819 DOI: 10.1016/j.livres.2022.02.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/08/2022] [Accepted: 02/27/2022] [Indexed: 12/19/2022]
Abstract
Portopulmonary hypertension (POPH) is a severe pulmonary vascular disease secondary to portal hypertension and a subset of Group 1 pulmonary hypertension (PH). The pathological changes of POPH are indistinguishable from other PH phenotypes, including endothelial dysfunction, pulmonary vasoconstriction, and vascular remodeling. These changes cause a progressive increase in pulmonary vascular resistance and afterload of the right ventricle, eventually leading to severe right heart failure. The prognosis of POPH is extremely poor among untreated patients. POPH is associated with a high risk of death after liver transplantation (LT), and severe POPH is considered an absolute contraindication for LT. However, pulmonary arterial hypertension (PAH)-targeted therapies are administered to patients with POPH, and aggressive drug treatment significantly optimizes pulmonary hemodynamics and reduces the risk of death. Therefore, early diagnosis, aggressive PAH-targeted therapies, and proper selection of liver transplant candidates are vital to reduce the risk of surgery and improve clinical outcomes. This article aims to review the results of previous studies and describe biological mechanisms, epidemiology, potential risk factors, and diagnostic approaches of POPH. Moreover, we introduce recent therapeutic interventions for the early diagnosis of POPH and efficient clinical management decisions.
Collapse
Affiliation(s)
- Huawei Xu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Baoquan Cheng
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Renren Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Mengmeng Ding
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yanjing Gao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| |
Collapse
|
|
43
|
Treatment of Portopulmonary Hypertension (PoPH): A Review. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2022.100071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
|
|
44
|
Cheron C, McBride SA, Antigny F, Girerd B, Chouchana M, Chaumais MC, Jaïs X, Bertoletti L, Sitbon O, Weatherald J, Humbert M, Montani D. Sex and gender in pulmonary arterial hypertension. Eur Respir Rev 2021; 30:30/162/200330. [PMID: 34750113 DOI: 10.1183/16000617.0330-2020] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 01/28/2021] [Indexed: 12/21/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and elevated pulmonary pressure, which eventually leads to right heart failure and death. Registries worldwide have noted a female predominance of the disease, spurring particular interest in hormonal involvement in the disease pathobiology. Several experimental models have shown both protective and deleterious effects of oestrogens, suggesting that complex mechanisms participate in PAH pathogenesis. In fact, oestrogen metabolites as well as receptors and enzymes implicated in oestrogen signalling pathways and associated conditions such as BMPR2 mutation contribute to PAH penetrance more specifically in women. Conversely, females have better right ventricular function, translating to a better prognosis. Along with right ventricular adaptation, women tend to respond to PAH treatment differently from men. As some young women suffer from PAH, contraception is of particular importance, considering that pregnancy in patients with PAH is strongly discouraged due to high risk of death. When contraception measures fail, pregnant women need a multidisciplinary team-based approach. This article aims to review epidemiology, mechanisms underlying the higher female predominance, but better prognosis and the intricacies in management of women affected by PAH.
Collapse
Affiliation(s)
- Céline Cheron
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Susan Ainslie McBride
- Internal Medicine Residency Program, Dept of Medicine, University of Calgary, Calgary, Canada
| | - Fabrice Antigny
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Barbara Girerd
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Margot Chouchana
- Assistance Publique Hôpitaux de Paris, Service de Pharmacie Hôpital Bicêtre, Le Kremlin Bicêtre, France
| | - Marie-Camille Chaumais
- Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.,Assistance Publique Hôpitaux de Paris, Service de Pharmacie Hôpital Bicêtre, Le Kremlin Bicêtre, France.,Université Paris-Saclay, Faculté de Pharmacie, Chatenay Malabry, France
| | - Xavier Jaïs
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Laurent Bertoletti
- Centre Hospitalier Universitaire de Saint-Etienne, Service de Médecine Vasculaire et Thérapeutique, Saint-Etienne, France.,INSERM U1059 et CIC1408, Université Jean-Monnet, Saint-Etienne, France
| | - Olivier Sitbon
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Jason Weatherald
- Division of Respirology, Dept of Medicine, University of Calgary, Calgary, Canada.,Libin Cardiovascular Institute, University of Calgary, Calgary, Canada
| | - Marc Humbert
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - David Montani
- School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France .,Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| |
Collapse
|
|
45
|
Akahane T. Factors associated with portopulmonary hypertension. Hepatol Res 2021; 51:1179-1180. [PMID: 34850499 DOI: 10.1111/hepr.13721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Takemi Akahane
- Department of Gastroenterology, Nara Medical University, Nara, Japan
| |
Collapse
|
|
46
|
Kawaguchi T, Honda A, Sugiyama Y, Nakano D, Tsutsumi T, Tahara N, Torimura T, Fukumoto Y. Association between the albumin-bilirubin (ALBI) score and severity of portopulmonary hypertension (PoPH): A data-mining analysis. Hepatol Res 2021; 51:1207-1218. [PMID: 34534392 DOI: 10.1111/hepr.13714] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Portopulmonary hypertension (PoPH) is a severe complication of chronic liver disease. We aimed to investigate the etiology of chronic liver disease and the factors associated with the severity of PoPH. SUBJECTS AND METHODS Echocardiography was undergone in 833 patients with chronic liver disease during 2005-2019 and 13 patients (1.6%) were diagnosed with PoPH in this observational study. At the diagnosis of PoPH, liver function was evaluated by albumin-bilirubin (ALBI) score. Severe PoPH was defined as (1) mean pulmonary arterial pressure (mPAP) ≥50 mmHg or (2) mPAP: 35-49 mmHg and pulmonary vascular resistance ≥400 dyne/s/cm5 . Factors associated with severe PoPH were evaluated by decision-tree analysis. RESULTS In patients with PoPH, the leading etiology of chronic liver disease was hepatitis C virus (HCV) (46.2% [sustained virological response (SVR): 23.1% and non-SVR: 15.4%]). Severe PoPH was observed in 53.8% of patients and the 5-year survival rate was 48.1%. There was a significant correlation of mPAP with ALBI score (r = 0.6456, p = 0.0171). In the decision-tree and random forest analyses, the most impacted classifier for severe PoPH was the ALBI score. In patients with ALBI score ≥-1.45, all patients showed severe PoPH, while the prevalence of severe PoPH was 25.0% in patients with ALBI score <-1.45. CONCLUSIONS We found that HCV including SVR was the major etiology of chronic liver disease in patients with PoPH. Moreover, we revealed that the ALBI score was the most impacted factor associated with severe PoPH. Thus, ALBI score may be useful for the estimation of pulmonary vascular resistance.
Collapse
Affiliation(s)
- Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Akihiro Honda
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yoichi Sugiyama
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Nobuhiro Tahara
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| |
Collapse
|
|
47
|
Del Valle K, DuBrock HM. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Pulmonary Vascular Complications of Liver Disease. Compr Physiol 2021; 11:3281-3302. [PMID: 34636408 DOI: 10.1002/cphy.c210009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pulmonary vascular disease is a frequent complication of chronic liver disease and portal hypertension, affecting up to 30% of patients. There are two distinct pulmonary vascular complications of liver disease: hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). HPS affects 25% of patients with chronic liver disease and is characterized by intrapulmonary vasodilatation and abnormal arterial oxygenation. HPS negatively impacts quality of life and is associated with a 2-fold increased risk of death compared to controls with liver disease without HPS. Angiogenesis, endothelin-1 mediated endothelial dysfunction, monocyte influx, and alveolar type 2 cell dysfunction seem to play important roles in disease pathogenesis but there are currently no effective medical therapies. Fortunately, HPS resolves following liver transplant (LT) with improvements in hypoxemia. POPH is a subtype of pulmonary arterial hypertension (PAH) characterized by an elevated mean pulmonary arterial pressure and pulmonary vascular resistance in the setting of normal left-sided filling pressures. POPH affects 5% to 6% of patients with chronic liver disease. Although the pathogenesis has not been fully elucidated, endothelial dysfunction, inflammation, and estrogen signaling have been identified as key pathways involved in disease pathogenesis. POPH is typically treated with PAH targeted therapy and may also improve with liver transplantation in selected patients. This article highlights what is currently known regarding the diagnosis, management, pathobiology, and outcomes of HPS and POPH. Ongoing research is needed to improve understanding of the pathophysiology and outcomes of these distinct and often misunderstood pulmonary vascular complications of liver disease. © 2021 American Physiological Society. Compr Physiol 11:1-22, 2021.
Collapse
|
|
48
|
Lahm T. Hormones, Hemodynamics, and Hepatic Function: Digesting the Intricacies of Sex Differences in Portopulmonary Hypertension. Chest 2021; 159:11-13. [PMID: 33422194 DOI: 10.1016/j.chest.2020.09.240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 09/16/2020] [Indexed: 11/29/2022] Open
Affiliation(s)
- Tim Lahm
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, and the Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine; and the Richard L. Roudebush VA Medical Center, Indianapolis, IN.
| |
Collapse
|
|
49
|
Prevalence and Associated Factors of Portopulmonary Hypertension in Patients with Portal Hypertension: A Case-Control Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5595614. [PMID: 33987440 PMCID: PMC8079202 DOI: 10.1155/2021/5595614] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/10/2021] [Accepted: 03/25/2021] [Indexed: 02/05/2023]
Abstract
Background and Aims There are few studies on the prevalence and clinical characteristics of portopulmonary hypertension (POPH) in patients with portal hypertension. In addition, invasive right heart catheterization further limits the clinical diagnosis of POPH patients. Methods From January 2018 to December 2019, 1004 patients with portal hypertension were treated in the Department of Hepatology, the First Hospital of Jilin University. Based on the inclusion and exclusion criteria, 188 patients with portal hypertension were finally included. We collected complete clinical data, laboratory examinations, and imaging examinations. Patients were divided into a POPH group and a non-POPH group based on echocardiographic results. We calculated the prevalence of POPH in patients with portal hypertension. The differences in clinical characteristics of the two groups of patients were compared. Results The prevalence of POPH in patients with portal hypertension was 2.8%. Among the 188 patients with portal hypertension with fingertip oxygen saturation < 95% at rest, 28 patients had POPH (12 males and 16 females), with an average age of 63 ± 8, and 160 patients did not have POPH (110 males, 50 women), with an average age of 59 ± 11. The proportion of women in the POPH group (P < 0.01) and patients without liver cancer (P = 0.044) was high. Compared to patients without POPH, patients with POPH had lower hemoglobin (related to the severity of anemia, P < 0.01), higher creatinine (P < 0.05), and lower partial pressure of oxygen and carbon dioxide (P < 0.05). Patients with POPH had a higher incidence of atrial enlargement, ventricular enlargement, mitral valve regurgitation, tricuspid regurgitation, pulmonary artery widening, pericardial effusion, and aortic regurgitation than those without POPH. The risk of POPH did not increase with the aggravation of the Child-Pugh classification. Conclusion The prevalence of POPH in patients with portal hypertension is 2.8%. The proportion of women and nonliver cancer in POPH patients was higher than that in non-POPH patients. In addition, the POPH group had higher creatinine and lower hemoglobin, and echocardiography showed that POPH patients had more cardiac structural changes. In patients with portal hypertension, the risk in patients with POPH has nothing to do with the Child-Pugh classification and MELD score.
Collapse
|
|
50
|
Huang A, Kandhi S, Sun D. Roles of Genetic Predisposition in the Sex Bias of Pulmonary Pathophysiology, as a Function of Estrogens : Sex Matters in the Prevalence of Lung Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1303:107-127. [PMID: 33788190 DOI: 10.1007/978-3-030-63046-1_7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In addition to studies focused on estrogen mediation of sex-different regulation of systemic circulations, there is now increasing clinical relevance and research interests in the pulmonary circulation, in terms of sex differences in the morbidity and mortality of lung diseases such as inherent-, allergic- and inflammatory-based events. Thus, female predisposition to pulmonary artery hypertension (PAH) is an inevitable topic. To better understand the nature of sexual differentiation in the pulmonary circulation, and how heritable factors, in vivo- and/or in vitro-altered estrogen circumstances and changes in the live environment work in concert to discern the sex bias, this chapter reviews pulmonary events characterized by sex-different features, concomitant with exploration of how alterations of genetic expression and estrogen metabolisms trigger the female-predominant pathological signaling. We address the following: PAH (Sect.7.2) is characterized as an estrogenic promotion of its incidence (Sect. 7.2.2), as a function of specific germline mutations, and as an estrogen-elicited protection of its prognosis (Sect.7.2.1). More detail is provided to introduce a less recognized gene of Ephx2 that encodes soluble epoxide hydrolase (sEH) to degrade epoxyeicosatrienic acids (EETs). As a susceptible target of estrogen, Ephx2/sEH expression is downregulated by an estrogen-dependent epigenetic mechanism. Increases in pulmonary EETs then evoke a potentiation of PAH generation, but mitigation of its progression, a phenomenon similar to the estrogen-paradox regulation of PAH. Additionally, the female susceptibility to chronic obstructive pulmonary diseases (Sect. 7.3) and asthma (Sect.7.4), but less preference to COVID-19 (Sect. 7.5), and roles of estrogen in their pathogeneses are briefly discussed.
Collapse
Affiliation(s)
- An Huang
- Department of Physiology, New York Medical College, Valhalla, NY, USA.
| | - Sharath Kandhi
- Department of Physiology, New York Medical College, Valhalla, NY, USA
| | - Dong Sun
- Department of Physiology, New York Medical College, Valhalla, NY, USA
| |
Collapse
|