Journal of Clinical and Experimental Hepatology最新文献

{"title":"Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis","authors":"Syed H. Ali ,&nbsp;Muhammad H. Shah ,&nbsp;Sakshi Roy ,&nbsp;Hareesha R. Bharadwaj ,&nbsp;Joecelyn K. Tan ,&nbsp;Medha S. Rao ,&nbsp;Muhtasim Fuad ,&nbsp;Arjun Ahluwalia ,&nbsp;Aditya Gaur ,&nbsp;Priyal Dalal ,&nbsp;Arkadeep Dhali ,&nbsp;Harishankar Gopakumar","doi":"10.1016/j.jceh.2025.102541","DOIUrl":"10.1016/j.jceh.2025.102541","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Chronic hepatitis B virus remains a significant cause of liver disease in the developing world, leading to sequelae such as hepatocellular carcinoma. While entecavir (ETV) serves as a first-line treatment, its growing resistance rates underscore the need to explore viable alternatives. Tenofovir disoproxil fumarate (TDF) monotherapy and entecavir plus tenofovir (TDF + ETV) combination therapy are both employed as treatments, but one's efficacy over another is in question. This meta-analysis aims to investigate any primacy of either treatment.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature search across PubMed/Medline, Embase, Cochrane Central, Web of Science, and China National Knowledge Infrastructure from inception till 7th October 2024. Studies comparing the safety and efficacy of TDF monotherapy versus TDF + ETV combination therapy in patients resistant to entecavir were considered. Data about the virologic response (VR), virologic breakthrough, HbeAg seroconversion, HbeAg/HbsAg seroclearance, and alanine aminotransferase normalization were extracted. Relative risks (RRs) and their corresponding 95% confidence intervals (CIs) were calculated, pooled, and analyzed in a random-effects model. <em>P</em>-value &lt;0.05 was regarded as significant for all analyses.</div></div><div><h3>Results</h3><div>Nine studies, comprising 335 patients undergoing monotherapy and 352 patients undergoing combination therapy, satisfied the criteria. TDF + ETV combination therapy was found slightly advantageous to TDF monotherapy, stimulating a VR at 48 weeks (RR 1.081 95% CI: [1.001–1.167] <em>P</em> = 0.046, I2 = 0%), along with the HbeAg seroconversion rate (RR 1.711 95% CI: [1.005–2.913] <em>P</em> = 0.048, I2 = 0%). There were no significant adverse events in individual studies to warrant a meta-analysis.</div></div><div><h3>Conclusions</h3><div>TDF + ETV shows slightly better efficacy to TDF monotherapy over a 48-week treatment regimen, with minimal safety concerns. However, further high-quality studies like randomized controlled trials are needed to further solidify conclusions, with this meta-analysis only achieving borderline significances.</div></div><div><h3>Registration</h3><div>This review is registered on the PROSPERO database (ID: CRD42024581443).</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102541"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the Complexities of Hepatocellular Carcinoma Management: Optimizing Liver Transplantation Outcomes Through a Multifaceted Approach","authors":"Sumana Kolar Ramachandra,&nbsp;G. Venkata Rao","doi":"10.1016/j.jceh.2025.102548","DOIUrl":"10.1016/j.jceh.2025.102548","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 3","pages":"Article 102548"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of Mortality in Patients Diagnosed With Autoimmune Hepatitis – Insights from a Prospective, 90-day Follow--up Study","authors":"Harsh J. Gandhi ,&nbsp;Shubham Jain ,&nbsp;Sanjay Chandnani ,&nbsp;Rishikesh N. Malokar ,&nbsp;Jay Chudasama ,&nbsp;Sameet Patel ,&nbsp;Deepika Pandey ,&nbsp;Vishal Mavuri ,&nbsp;Rima Kamat ,&nbsp;Pravin Rathi","doi":"10.1016/j.jceh.2025.102546","DOIUrl":"10.1016/j.jceh.2025.102546","url":null,"abstract":"<div><h3>Background and aims</h3><div>The response to corticosteroids and optimal timing for liver transplantation (LT) in patients with autoimmune hepatitis (AIH) remain significant clinical challenges. This study aimed to assess short-term (90-day) mortality in patients with acute AIH (with or without underlying cirrhosis and chronic liver disease) treated with corticosteroids, and to identify factors that predict mortality in this population.</div></div><div><h3>Methods</h3><div>We conducted a prospective, single-center study between 2022 and 2024, involving patients with histologically confirmed AIH. All patients received corticosteroid treatment and were monitored for various clinical and laboratory parameters on days 3, 7, and 90 after initiating therapy.</div></div><div><h3>Results</h3><div>A total of 104 patients were included in the study, with a mean age of 46.1 ± 14.3 years; 77% of the patients were female. The 90-day mortality rate following the initiation of corticosteroids was 13.47%. Univariate analysis identified several significant predictors of mortality, including older age, diabetes mellitus, cirrhosis, esophageal varices, hepatic encephalopathy, low serum albumin on day 3, model of end-stage liver disease (MELD) scores on days 3 and 7, and the survival and prognostic factors for acute severe autoimmune hepatitis (SURFASA) score (<em>P</em> &lt; 0.05). Multivariate analysis revealed that MELD score on day 7 (odds ratio [OR] 1.25; 95% confidence interval [CI] {1.09–1.48}; <em>P</em> = 0.00) and SURFASA score (OR 7.46; 95% CI {1.05–53.06}; <em>P</em> = 0.04) were significant. Specifically, a MELD score ≥27.5 on day 7 (area under the receiver operating characteristic curve [AUC] = 0.998) with 100% sensitivity and 97.8% specificity, and a SURFASA score ≥ −2.95 (AUC = 0.969) with 100% sensitivity and 95.6% specificity were highly predictive of mortality.</div></div><div><h3>Conclusion</h3><div>Despite corticosteroid treatment, mortality rates remain high in the decompensated AIH and acute on chronic liver failure–AIH groups. The SURFASA score, along with MELD scores on days 3 and 7, are strong predictors of mortality and can assist clinicians in making timely decisions regarding referral for early liver transplantation.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102546"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic and Alcohol-associated Liver Disease and its Place in the Spectrum of Steatotic Liver Disease","authors":"Stephanie M. Rutledge,&nbsp;Gene Y. Im","doi":"10.1016/j.jceh.2025.102545","DOIUrl":"10.1016/j.jceh.2025.102545","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 3","pages":"Article 102545"},"PeriodicalIF":3.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of Two Prognostic Gene Scores in Patients Undergoing Liver Resection for Hepatocellular Carcinoma","authors":"Stinna D. Schnabl ,&nbsp;Jeanett Klubien ,&nbsp;Colm J. O'Rourke ,&nbsp;Sophie Bull Nordkild ,&nbsp;Jan-Michael Kugler ,&nbsp;Susanne Dam Nielsen ,&nbsp;Jesper B. Andersen ,&nbsp;Hans-Christian Pommergaard","doi":"10.1016/j.jceh.2025.102544","DOIUrl":"10.1016/j.jceh.2025.102544","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Several prognostic gene signatures have been proposed as predictors of the prognosis of hepatocellular carcinoma (HCC), yet none are implemented in the clinical setting. We aimed to validate two gene scores previously derived from European cohorts.</div></div><div><h3>Methods</h3><div>The patients who underwent liver resection for HCC at Copenhagen University Hospital, Rigshospitalet from 2014 to 2018 were included. RNA sequencing determined the expression of genes in the ‘<em>5-gene score</em>’ (<em>HN1, RAN, RAMP3, KRT19, TAF9B</em>) and ‘<em>HepatoPredict’</em> (<em>CLU, DPT, SPRY2, CAPSN1</em>). Univariable Cox regression assessed associations with overall and disease-free survival. These parameters were also analyzed in the The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) (n = 359) and National Institute of Health (NIH) (n = 178) cohorts.</div></div><div><h3>Results</h3><div>Among 51 patients (88% male), 59% had no underlying liver disease and 25% had cirrhosis. No individual genes were significantly associated with overall survival in the Danish cohort. In the TCGA-LIHC cohort, <em>CLU</em> was linked to better overall survival, and in the NIH cohort, high expression of <em>SPRY2</em> was associated with poorer overall survival. In the TCGA-LIHC cohort, <em>HN1</em>, <em>RAN</em>, and <em>TAF9B</em> were associated with poorer overall survival, while <em>RAMP3</em> was linked to better overall survival. No genes were associated with disease-free survival.</div></div><div><h3>Conclusion</h3><div>Few individual genes significantly predicted survival in the larger cohorts, and none in the Danish cohort. However, the clinical implication of this needs further investigation.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102544"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Transient Elastography in Differentiating Biliary Atresia from Other Causes of Neonatal Cholestasis: A Prospective Observational Study","authors":"Upasana Ghosh ,&nbsp;Ujjal Poddar ,&nbsp;Narendra Krishnani ,&nbsp;Vivek A. Saraswat ,&nbsp;Basant Kumar ,&nbsp;Moinak S. Sarma ,&nbsp;Anshu Srivastava ,&nbsp;Prabhaker Mishra","doi":"10.1016/j.jceh.2025.102543","DOIUrl":"10.1016/j.jceh.2025.102543","url":null,"abstract":"<div><h3>Background</h3><div>Differentiating biliary atresia (BA) from non-BA is paramount, as their management and outcome differ. So far, BA is diagnosed by intraoperative cholangiogram (IOC) or liver biopsy. However, literature is sparse on the utility of transient elastography (TE) in neonatal cholestasis. We aimed to study the usefulness and accuracy of TE in differentiating BA from other causes of neonatal cholestasis (NCS).</div></div><div><h3>Methods</h3><div>A prospective observational study was conducted from June 2021 to February 2024; consecutive cases of NCS were recruited. Patients were grouped as BA and non-BA. All patients underwent clinical, laboratory, and radiological evaluation, along with TE. Receiver operating characteristic curve (ROC) analysis was performed to derive an LSM cutoff for diagnosing BA. The liver stiffness measurement (LSM) was correlated with histopathological fibrosis.</div></div><div><h3>Results</h3><div>We enrolled 135 patients, BA (n = 68) and non-BA (n = 67). The median LSM was higher in BA, 19.4 (12.9–38.75) kPa <em>vs</em>. 12.0 (8.4–17.9) kPa (<em>P</em>=&lt;0.001). LSM positively correlated with the METAVIR fibrosis score (Spearman's correlation coefficient, r = 0.590, <em>P</em> &lt; 0.001). We derived an LSM cutoff of 13.1 kPa to differentiate BA from non-BA (sensitivity 75%, specificity 61.2%, AUC 0.736). By adding ultrasound (USG) finding of a small gallbladder (&lt;19 mm) to our LSM cutoff (13.1 kPa), the sensitivity improved to 97.0%, but specificity remained low (52.2%).</div></div><div><h3>Conclusion</h3><div>LSM correlates well with histopathological fibrosis in NCS. An LSM cut off of 13.1 kPa can be used to differentiate BA from non-BA with a sensitivity of 75%. In resource-constraint setting where liver biopsy and IOC may not be available, TE in combination with USG can be a good screening tool for BA (sensitivity 97%).</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102543"},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unearthing TULP3 Mutation as a Rare Cause of Cryptogenic Cirrhosis: A Case Report and Review of the Literature","authors":"Arpit Shastri ,&nbsp;S. Balaraja ,&nbsp;Arka De ,&nbsp;Suvradeep Mitra ,&nbsp;Ajay Duseja","doi":"10.1016/j.jceh.2025.102542","DOIUrl":"10.1016/j.jceh.2025.102542","url":null,"abstract":"<div><div>Whole-exome sequencing may help unearth uncommon monogenic causes of cryptogenic cirrhosis and portal hypertension. Tubby-like protein 3 (<em>TULP3)</em> gene encodes the tubby domain family of proteins, mutations of which is associated with progressive degenerative disease of major organs such as kidney, heart, and liver. Here we report a case of a young male with decompensated cirrhosis who was ultimately identified with homozygous pathogenic splice donor variant c.492+1G &gt; A in intron 5 of <em>TULP3</em> gene.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102542"},"PeriodicalIF":3.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transarterial Chemoembolization: A Consistent and Continuously Evolving Therapy for Hepatocellular Carcinoma","authors":"Amar Mukund,&nbsp;Niraj Kumar,&nbsp;Amol Srivastava,&nbsp;Akhil Baby","doi":"10.1016/j.jceh.2025.102538","DOIUrl":"10.1016/j.jceh.2025.102538","url":null,"abstract":"<div><div>Since its introduction in 1977, transarterial chemoembolization (TACE) has widely been accepted treatment for unresectable intermediate stage hepatocellular carcinoma (HCC). Conventional TACE (c-TACE) uses an emulsion of chemotherapeutic agent and ethiodized oil with subsequent embolization of the feeding artery using gelatin sponge. Drug eluting beads (DEB) were introduced in clinical practice in the 2000s and have since been used as an alternative to c-TACE with better outcomes, especially in larger tumors. Considering the widespread use of TACE in HCC, it is important to revisit the current knowledge and the advances that have developed for better safety and efficacy. This article aims to emphasize on the current knowledge and importance of TACE, touch upon the technical aspects including post-TACE care, response assessment, and discontinuation strategies and highlight the recent advances in the technology, catheters, and embolization particles. Thus, despite a rapid change in treatment algorithms and availability of newer drugs for HCC, TACE will remain an integral part of HCC treatment alone or in combination with other therapies.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102538"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Differences in Risk of Cirrhosis or Hepatocellular Carcinoma Among Treatment Naïve Chronic Hepatitis B Patients by Baseline Hepatitis B Viral Load: A Propensity Score Weighted Analysis","authors":"Zeyuan Yang ,&nbsp;Ramsey C. Cheung ,&nbsp;Janice H. Jou ,&nbsp;Joseph K. Lim ,&nbsp;Robert J. Wong","doi":"10.1016/j.jceh.2025.102540","DOIUrl":"10.1016/j.jceh.2025.102540","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Previous studies among Korean adults with treatment-naïve chronic hepatitis B (CHB) observed paradoxical relationships between baseline hepatitis B virus (HBV) DNA and risk of hepatocellular carcinoma (HCC). However, these observations have not been validated in Western cohorts. We aim to evaluate the longitudinal risk of cirrhosis or HCC among a national cohort of treatment-naïve patients with noncirrhotic chronic HBV.</div></div><div><h3>Methods</h3><div>Using a national cohort of U.S. Veterans with CHB (with baseline HBV DNA ≥2000 IU/mL) from 1/1/2020 to 3/31/2024, we evaluated the long-term risk of cirrhosis or HCC stratified by baseline high HBV DNA (&gt;6.00 log₁₀ IU/mL) or moderate HBV DNA (2000–6.00 log₁₀ IU/mL). We applied propensity score weighting methods to adjust for baseline differences between the two groups.</div></div><div><h3>Results</h3><div>A total of 1198 noncirrhotic treatment-naïve CHB patients with HBV DNA ≥2000 IU/mL were identified (90.7% were men, 41.7% African American, 29.6% non-Hispanic white, 18.2% Asian, mean age was 54.7 years, 27.9% were HBeAg positive). After propensity score weighting was applied, no significant differences in the incidence of cirrhosis or HCC were observed between CHB patients with moderate vs. high baseline HBV DNA (cirrhosis: 1.02 (95% CI: 0.83–1.25) vs. 1.19 per 100 person-years (95% CI: 0.94–1.51); HR 0.93, 95% CI: 0.68–1.28, <em>P</em> = 0.66; HCC: 0.34 (95% CI: 0.24–0.48) vs. 0.29 per 100 person-years (95% CI: 0.18–0.46); HR 1.02, 95% CI: 1.83, <em>P</em> = 0.95).</div></div><div><h3>Conclusions</h3><div>Among a national cohort of Western, predominantly non-Asian patients with treatment-naïve CHB, no significant differences in risk of cirrhosis or HCC were observed by baseline HBV DNA. These data suggest that some epidemiological trends and associations observed in Asian CHB populations may not necessarily be generalizable to non-Asian cohorts with different modes of transmission, risk factors, and virus-specific characteristics.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 4","pages":"Article 102540"},"PeriodicalIF":3.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Highlights","authors":"","doi":"10.1016/S0973-6883(25)00030-1","DOIUrl":"10.1016/S0973-6883(25)00030-1","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"Article 102530"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}