Pub Date : 2025-12-09DOI: 10.1016/j.jceh.2025.103418
Rohan Grotra , Prasenjit Das , Rajni Yadav , Lalita Mehra , Ashok Tiwari , Rohan Malik
Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is a rare autosomal recessive disorder caused by mutations in the ABCB11 gene, which encodes the bile salt export pump (BSEP). Liver transplantation is the standard treatment for end-stage liver disease in PFIC-2; however, recurrence in the form of autoimmune BSEP disease (AIBD) is a recognized posttransplant complication. AIBD is characterized by cholestasis with normal gamma-glutamyl transpeptidase, severe pruritus, and the presence of anti-BSEP antibodies. We report a case of a PFIC-2 patient who developed recurrent cholestasis and pruritus three years posttransplant. Liver biopsy revealed canalicular cholestasis and giant cell transformation, while BSEP staining on immunohistochemistry was preserved. Serological testing confirmed anti-BSEP antibody positivity. Despite aggressive therapy including plasmapheresis, intravenous immunoglobulin, and rituximab, only partial improvement was achieved, and cholestasis persisted. Given the refractory nature of the disease, bortezomib—a proteasome inhibitor targeting antibody-producing plasma cells—was administered. The patient demonstrated complete clinical and biochemical resolution following bortezomib therapy. This case highlights the diagnostic complexity of AIBD and the potential role of bortezomib in cases unresponsive to conventional immunosuppressive therapies. Early diagnosis and personalized immunomodulation remain key to improving outcomes in this rare but challenging condition.
{"title":"Bortezomib Therapy in Autoimmune-BSEP Disease After Liver Transplantation: Case Report With Review of the Literature","authors":"Rohan Grotra , Prasenjit Das , Rajni Yadav , Lalita Mehra , Ashok Tiwari , Rohan Malik","doi":"10.1016/j.jceh.2025.103418","DOIUrl":"10.1016/j.jceh.2025.103418","url":null,"abstract":"<div><div>Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is a rare autosomal recessive disorder caused by mutations in the <em>ABCB11</em> gene, which encodes the bile salt export pump (BSEP). Liver transplantation is the standard treatment for end-stage liver disease in PFIC-2; however, recurrence in the form of autoimmune BSEP disease (AIBD) is a recognized posttransplant complication. AIBD is characterized by cholestasis with normal gamma-glutamyl transpeptidase, severe pruritus, and the presence of anti-BSEP antibodies. We report a case of a PFIC-2 patient who developed recurrent cholestasis and pruritus three years posttransplant. Liver biopsy revealed canalicular cholestasis and giant cell transformation, while BSEP staining on immunohistochemistry was preserved. Serological testing confirmed anti-BSEP antibody positivity. Despite aggressive therapy including plasmapheresis, intravenous immunoglobulin, and rituximab, only partial improvement was achieved, and cholestasis persisted. Given the refractory nature of the disease, bortezomib—a proteasome inhibitor targeting antibody-producing plasma cells—was administered. The patient demonstrated complete clinical and biochemical resolution following bortezomib therapy. This case highlights the diagnostic complexity of AIBD and the potential role of bortezomib in cases unresponsive to conventional immunosuppressive therapies. Early diagnosis and personalized immunomodulation remain key to improving outcomes in this rare but challenging condition.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103418"},"PeriodicalIF":3.2,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881175","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}
Pub Date : 2025-12-03DOI: 10.1016/j.jceh.2025.103432
Ajeet S. Bhadoria , Amrita Mehndiratta , Kathirvel Soundappan , Rajesh Somvanshi , Muhammad S. Jamil , Niklas Luhmann
Background/Aims
Globally, only 36% of people with hepatitis C are aware of their infection, and just 20% of those diagnosed receive treatment, highlighting a significant diagnosis and treatment gap. The World Health Organization recommends hepatitis C virus self-testing (HCVST) as an additional strategy to increase access to diagnosis.
Methods
From July 2023 to April 2024, we conducted a cross-sectional study nested within a larger cluster randomized control trial (RCT) (CTRI/2023/07/054590) in urban slums of Haridwar. A total of 465 participants were recruited from community and urban primary health center settings. Under observation, participants performed hepatitis C virus (HCV) self-testing, allowing assessment of usability by tracking errors using standardized checklists, user-reported difficulties, and inter-reader concordance (self vs. trained personnel interpretation). For acceptability, a pre-tested questionnaire collected socio-demographic data, risk factors for HCV, participant experiences, and responses to hypothetical test results. Additionally, 35 ELISA-positive individuals were recruited to assess the sensitivity and specificity of the self-testing kit.
Results
Participants, mostly aged 26–35 years with primary education, demonstrated high usability, over 90% correctly performed critical steps like finger pricking, and 96% interpreted results accurately. Participants with education beyond high school had better interpretation accuracy (98.8% vs. 94.4%, P = 0.02). The process was reported as significantly easier by males (85.2% vs. 71.9%), participants under 46 years (82.4% vs. 66.1%), and those with higher education (90.1% vs. 71.6%, P < 0.001). Satisfaction was high (94.2%), and 95.4% trusted the test's accuracy. Inter-reader concordance was 95.9% (Cohen's Kappa = 0.25; 95% confidence interval [CI]: 0.07–0.43). Sensitivity and specificity were 97.4% and 99.6%, respectively.
Conclusion
The HCV self-testing was highly usable and acceptable among residents of urban slums. While participants valued privacy and convenience, challenges with blood collection, instructions, and the absence of counseling were noted. HCV self-testing, if scaled up through targeted rollout and linked to counselling and treatment services, could substantially narrow the diagnostic gap and accelerate India's progress toward HCV elimination.
{"title":"Assessment of Usability and Acceptability of Blood-based Hepatitis C Virus Self-testing Among Residents of Urban Slums in Northern India: A Cross-sectional Study","authors":"Ajeet S. Bhadoria , Amrita Mehndiratta , Kathirvel Soundappan , Rajesh Somvanshi , Muhammad S. Jamil , Niklas Luhmann","doi":"10.1016/j.jceh.2025.103432","DOIUrl":"10.1016/j.jceh.2025.103432","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Globally, only 36% of people with hepatitis C are aware of their infection, and just 20% of those diagnosed receive treatment, highlighting a significant diagnosis and treatment gap. The World Health Organization recommends hepatitis C virus self-testing (HCVST) as an additional strategy to increase access to diagnosis.</div></div><div><h3>Methods</h3><div>From July 2023 to April 2024, we conducted a cross-sectional study nested within a larger cluster randomized control trial (RCT) (CTRI/2023/07/054590) in urban slums of Haridwar. A total of 465 participants were recruited from community and urban primary health center settings. Under observation, participants performed hepatitis C virus (HCV) self-testing, allowing assessment of usability by tracking errors using standardized checklists, user-reported difficulties, and inter-reader concordance (self vs. trained personnel interpretation). For acceptability, a pre-tested questionnaire collected socio-demographic data, risk factors for HCV, participant experiences, and responses to hypothetical test results. Additionally, 35 ELISA-positive individuals were recruited to assess the sensitivity and specificity of the self-testing kit.</div></div><div><h3>Results</h3><div>Participants, mostly aged 26–35 years with primary education, demonstrated high usability, over 90% correctly performed critical steps like finger pricking, and 96% interpreted results accurately. Participants with education beyond high school had better interpretation accuracy (98.8% vs. 94.4%, <em>P</em> = 0.02). The process was reported as significantly easier by males (85.2% vs. 71.9%), participants under 46 years (82.4% vs. 66.1%), and those with higher education (90.1% vs. 71.6%, <em>P</em> < 0.001). Satisfaction was high (94.2%), and 95.4% trusted the test's accuracy. Inter-reader concordance was 95.9% (Cohen's Kappa = 0.25; 95% confidence interval [CI]: 0.07–0.43). Sensitivity and specificity were 97.4% and 99.6%, respectively.</div></div><div><h3>Conclusion</h3><div>The HCV self-testing was highly usable and acceptable among residents of urban slums. While participants valued privacy and convenience, challenges with blood collection, instructions, and the absence of counseling were noted. HCV self-testing, if scaled up through targeted rollout and linked to counselling and treatment services, could substantially narrow the diagnostic gap and accelerate India's progress toward HCV elimination.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103432"},"PeriodicalIF":3.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837968","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}
Pub Date : 2025-12-02DOI: 10.1016/j.jceh.2025.103431
Diego F. Wyszynski
Background and Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition characterized by excess hepatic fat accumulation in the absence of significant hepatocellular injury. Its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), includes hepatic inflammation and hepatocellular ballooning and may progress to fibrosis or cirrhosis. Although MASLD appears to be slightly less prevalent in pregnant individuals than in the general population, emerging evidence suggests clinically meaningful associations with adverse maternal and neonatal outcomes. This review aims to summarize current evidence on the epidemiology, clinical implications, and management of MASLD during pregnancy.
Methods
A narrative review of the published literature was conducted to evaluate data on MASLD and MASH in pregnancy, including associations with maternal metabolic conditions, obstetric and neonatal outcomes, disease severity, screening considerations, and available therapeutic approaches.
Results
MASLD during pregnancy has been associated with an increased risk of adverse maternal and neonatal outcomes and demonstrates a bidirectional relationship with gestational diabetes mellitus. Several studies suggest a dose–response relationship, with greater MASLD severity corresponding to higher risks of complications. Despite these associations, routine screening for MASLD in pregnant populations is not currently recommended. Management remains centered on lifestyle interventions, including dietary modification and physical activity. Recently approved pharmacologic agents for MASH, such as resmetirom and semaglutide, represent important advances in non-pregnant populations; however, pregnancy-specific safety data for these therapies are lacking.
Conclusions
MASLD in pregnancy is an emerging clinical concern with important implications for maternal and fetal health. While lifestyle modification remains the cornerstone of management, the absence of pregnancy-specific safety data for newer pharmacologic therapies highlights a critical knowledge gap. Further research is urgently needed to clarify risk stratification, screening strategies, and safe therapeutic options for MASLD in pregnant populations.
{"title":"Non-alcoholic Fatty Liver Disease in Pregnancy: Clinical Implications, Adverse Outcomes, and Therapeutic Considerations","authors":"Diego F. Wyszynski","doi":"10.1016/j.jceh.2025.103431","DOIUrl":"10.1016/j.jceh.2025.103431","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition characterized by excess hepatic fat accumulation in the absence of significant hepatocellular injury. Its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), includes hepatic inflammation and hepatocellular ballooning and may progress to fibrosis or cirrhosis. Although MASLD appears to be slightly less prevalent in pregnant individuals than in the general population, emerging evidence suggests clinically meaningful associations with adverse maternal and neonatal outcomes. This review aims to summarize current evidence on the epidemiology, clinical implications, and management of MASLD during pregnancy.</div></div><div><h3>Methods</h3><div>A narrative review of the published literature was conducted to evaluate data on MASLD and MASH in pregnancy, including associations with maternal metabolic conditions, obstetric and neonatal outcomes, disease severity, screening considerations, and available therapeutic approaches.</div></div><div><h3>Results</h3><div>MASLD during pregnancy has been associated with an increased risk of adverse maternal and neonatal outcomes and demonstrates a bidirectional relationship with gestational diabetes mellitus. Several studies suggest a dose–response relationship, with greater MASLD severity corresponding to higher risks of complications. Despite these associations, routine screening for MASLD in pregnant populations is not currently recommended. Management remains centered on lifestyle interventions, including dietary modification and physical activity. Recently approved pharmacologic agents for MASH, such as resmetirom and semaglutide, represent important advances in non-pregnant populations; however, pregnancy-specific safety data for these therapies are lacking.</div></div><div><h3>Conclusions</h3><div>MASLD in pregnancy is an emerging clinical concern with important implications for maternal and fetal health. While lifestyle modification remains the cornerstone of management, the absence of pregnancy-specific safety data for newer pharmacologic therapies highlights a critical knowledge gap. Further research is urgently needed to clarify risk stratification, screening strategies, and safe therapeutic options for MASLD in pregnant populations.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103431"},"PeriodicalIF":3.2,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837966","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}
Pub Date : 2025-11-29DOI: 10.1016/j.jceh.2025.103422
Cyriac A. Philips, Tharun T. Oommen, Rizwan Ahamed, Ajit Tharakan, Philip Augustine
{"title":"“Facts are Stubborn Things, but Statistics are Pliable” —Concerns Regarding Meta-Analysis of Granulocyte Colony-Stimulating Factor Therapy in Severe Alcohol-Associated Hepatitis","authors":"Cyriac A. Philips, Tharun T. Oommen, Rizwan Ahamed, Ajit Tharakan, Philip Augustine","doi":"10.1016/j.jceh.2025.103422","DOIUrl":"10.1016/j.jceh.2025.103422","url":null,"abstract":"","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103422"},"PeriodicalIF":3.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789135","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}
Pub Date : 2025-11-29DOI: 10.1016/j.jceh.2025.103421
Amal Trigui , Crystèle Hogue , Mélanie Tremblay , Geneviève Huard , Christopher F. Rose , Chantal Bémeur
Background/Aims
Malnutrition, sarcopenia, and frailty negatively impact quality of life and increase mortality following liver transplantation (LT). However, long-term follow-up data remain limited. This study aimed primarily to assess the malnutrition risk at 1-, 2-, and 3-years post-LT. Secondary objectives included evaluating the sarcopenia and frailty risk, muscle function, physical activity, quality of life, and employment status at the same time points.
Methods
This cross-sectional study included LT recipients with a history of cirrhosis, transplanted between January 2019 and December 2021. Each participant completed a single virtual meeting during which nutritional risk, sarcopenia, frailty risk, muscle function, physical activity, quality of life, employment status, and dietary intakes were assessed.
Results
Sixty-six LT recipients (63.6% male) were included: cohort A (1-year post-LT, n = 25), cohort B (2 years post-LT, n = 14), and cohort C (3 years post-LT, n = 27). The prevalence of malnutrition (12.0%, 14.3%, and 11.1%), sarcopenia (16.0%, 28.6%, and 18.5%), and frailty risks (12.0%, 28.6%, and 18.5%) in cohorts A, B, and C, respectively, remained stable over time (P = 0.957, 0.626, and 0.436). Energy intake was a significant predictor of both malnutrition and sarcopenia, with muscle function predicting the risk of sarcopenia and frailty post-LT. Muscle function was lowest in cohort B and inferior in age-matched adults in all cohorts. One-third of patients had low physical activity levels, with no significant change across cohorts (P = 0.096). Quality of life remained unchanged, except for lower emotional well-being and health change scores in cohort C compared to cohort A (P = 0.039 and P < 0.001, respectively). Only 28.0%, 42.9%, and 25.9% of participants in cohorts A, B, and C, respectively, returned to work.
Conclusion
Up to 3 years after LT, patients were still at risk of malnutrition, sarcopenia, and frailty. The results of this study highlight the need for targeted interventions to improve outcomes and support long-term quality of life post-LT.
{"title":"Screening for Malnutrition, Sarcopenia, and Physical Frailty Beyond One Year after Liver Transplantation","authors":"Amal Trigui , Crystèle Hogue , Mélanie Tremblay , Geneviève Huard , Christopher F. Rose , Chantal Bémeur","doi":"10.1016/j.jceh.2025.103421","DOIUrl":"10.1016/j.jceh.2025.103421","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Malnutrition, sarcopenia, and frailty negatively impact quality of life and increase mortality following liver transplantation (LT). However, long-term follow-up data remain limited. This study aimed primarily to assess the malnutrition risk at 1-, 2-, and 3-years post-LT. Secondary objectives included evaluating the sarcopenia and frailty risk, muscle function, physical activity, quality of life, and employment status at the same time points.</div></div><div><h3>Methods</h3><div>This cross-sectional study included LT recipients with a history of cirrhosis, transplanted between January 2019 and December 2021. Each participant completed a single virtual meeting during which nutritional risk, sarcopenia, frailty risk, muscle function, physical activity, quality of life, employment status, and dietary intakes were assessed.</div></div><div><h3>Results</h3><div>Sixty-six LT recipients (63.6% male) were included: cohort A (1-year post-LT, n = 25), cohort B (2 years post-LT, n = 14), and cohort C (3 years post-LT, n = 27). The prevalence of malnutrition (12.0%, 14.3%, and 11.1%), sarcopenia (16.0%, 28.6%, and 18.5%), and frailty risks (12.0%, 28.6%, and 18.5%) in cohorts A, B, and C, respectively, remained stable over time (<em>P</em> = 0.957, 0.626, and 0.436). Energy intake was a significant predictor of both malnutrition and sarcopenia, with muscle function predicting the risk of sarcopenia and frailty post-LT. Muscle function was lowest in cohort B and inferior in age-matched adults in all cohorts. One-third of patients had low physical activity levels, with no significant change across cohorts (<em>P</em> = 0.096). Quality of life remained unchanged, except for lower emotional well-being and health change scores in cohort C compared to cohort A (<em>P</em> = 0.039 and <em>P</em> < 0.001, respectively). Only 28.0%, 42.9%, and 25.9% of participants in cohorts A, B, and C, respectively, returned to work.</div></div><div><h3>Conclusion</h3><div>Up to 3 years after LT, patients were still at risk of malnutrition, sarcopenia, and frailty. The results of this study highlight the need for targeted interventions to improve outcomes and support long-term quality of life post-LT.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103421"},"PeriodicalIF":3.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837969","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}
Pub Date : 2025-11-29DOI: 10.1016/j.jceh.2025.103423
Akshay B. Verma , Arihant Seth , Piyush Dadhich , Sunil K. Dadhich , Surender Kumar , Mohit S. Khokhar , Sabir Hussain , Sewaram Choudhary , Mahesh K. Sharma , Ramandeep Singh , Yaduvir S. Meena , Rampartap Swami
Background and aims
Liver fibrosis is a key prognostic factor in steatotic liver diseases (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and alcohol-associated liver disease (MetALD), and alcohol-related liver disease (ALD). This study aimed to (1) compare systemic inflammation and fibrosis across phenotypes, (2) study correlations between inflammatory markers and occurrence of fibrosis and (3) evaluate correlations between immune-inflammatory markers and fibrosis severity.
Methods
A total of 180 patients were categorized as MASLD (n = 69), MetALD (n = 43), and ALD (n = 68) based on the Delphi consensus. SLD was defined as hepatic steatosis on imaging in the presence of either metabolic dysfunction and/or alcohol exposure. Advanced fibrosis was defined as a liver stiffness measurement ≥12 kPa on transient elastography. FIB-4, APRI, Agile 3+ MELD, CTP scores, and systemic immune-inflammatory markers—neutrophil-to-lymphocyte ratio (NLR) and others, were assessed. Correlation analysis and multivariate logistic regression were performed. We derived a composite score using inflammatory markers, which identified patients with increased likelihood of advanced fibrosis, with high accuracy and a high positive predictive value.
Results
Out of 180 patients with SLD, ALD patients had the highest neutrophilic burden (mean NLR 6.56 ± 1.61), followed by MetALD (5.16 ± 1.36) and MASLD (4.30 ± 1.60) (P < 0.001). MASLD exhibited a lymphocyte–predominant profile (mean LMR 4.86 ± 1.17), as compared to MetALD (3.46 ± 0.74) and ALD (3.31 ± 0.98) (P < 0.001). A total of149 patients had advanced fibrosis. Fibrosis burden was highest in ALD (mean liver stiffness 27.43 ± 11.50 kPA), but it was similar in both MetALD (20.28 ± 14.29 kPA) and MASLD (20.49 ± 7.66 kPA).
Conclusion
Despite overlapping clinical features, MASLD, MetALD, and ALD exhibit distinct inflammatory profiles. Systemic immune-inflammatory markers, especially NLR, are closely associated with fibrosis severity. The developed Fibrosis-Inflammation Risk Model Score, offers a potentially scalable, cost-effective tool pending validation in broader real-world settings.
{"title":"Phenotype-specific Inflammatory Profiles in Steatotic Liver Disease: Implications for Identifying Fibrosis","authors":"Akshay B. Verma , Arihant Seth , Piyush Dadhich , Sunil K. Dadhich , Surender Kumar , Mohit S. Khokhar , Sabir Hussain , Sewaram Choudhary , Mahesh K. Sharma , Ramandeep Singh , Yaduvir S. Meena , Rampartap Swami","doi":"10.1016/j.jceh.2025.103423","DOIUrl":"10.1016/j.jceh.2025.103423","url":null,"abstract":"<div><h3>Background and aims</h3><div>Liver fibrosis is a key prognostic factor in steatotic liver diseases (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and alcohol-associated liver disease (MetALD), and alcohol-related liver disease (ALD). This study aimed to (1) compare systemic inflammation and fibrosis across phenotypes, (2) study correlations between inflammatory markers and occurrence of fibrosis and (3) evaluate correlations between immune-inflammatory markers and fibrosis severity.</div></div><div><h3>Methods</h3><div>A total of 180 patients were categorized as MASLD (n = 69), MetALD (n = 43), and ALD (n = 68) based on the Delphi consensus. SLD was defined as hepatic steatosis on imaging in the presence of either metabolic dysfunction and/or alcohol exposure. Advanced fibrosis was defined as a liver stiffness measurement ≥12 kPa on transient elastography. FIB-4, APRI, Agile 3+ MELD, CTP scores, and systemic immune-inflammatory markers—neutrophil-to-lymphocyte ratio (NLR) and others, were assessed. Correlation analysis and multivariate logistic regression were performed. We derived a composite score using inflammatory markers, which identified patients with increased likelihood of advanced fibrosis, with high accuracy and a high positive predictive value.</div></div><div><h3>Results</h3><div>Out of 180 patients with SLD, ALD patients had the highest neutrophilic burden (mean NLR 6.56 ± 1.61), followed by MetALD (5.16 ± 1.36) and MASLD (4.30 ± 1.60) (<em>P</em> < 0.001). MASLD exhibited a lymphocyte–predominant profile (mean LMR 4.86 ± 1.17), as compared to MetALD (3.46 ± 0.74) and ALD (3.31 ± 0.98) (<em>P</em> < 0.001). A total of149 patients had advanced fibrosis. Fibrosis burden was highest in ALD (mean liver stiffness 27.43 ± 11.50 kPA), but it was similar in both MetALD (20.28 ± 14.29 kPA) and MASLD (20.49 ± 7.66 kPA).</div></div><div><h3>Conclusion</h3><div>Despite overlapping clinical features, MASLD, MetALD, and ALD exhibit distinct inflammatory profiles. Systemic immune-inflammatory markers, especially NLR, are closely associated with fibrosis severity. The developed Fibrosis-Inflammation Risk Model Score, offers a potentially scalable, cost-effective tool pending validation in broader real-world settings.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103423"},"PeriodicalIF":3.2,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789073","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}
There is limited literature on the long-term outcomes of patients with cirrhosis following an index gastric variceal (GV) hemorrhage.
Methods
Patients with cirrhosis and hemorrhage from gastroesophageal varices type-2 (GOV-2) or isolated gastric varices type-1 (IGV-1) from two tertiary care centers over 8 years were retrospectively analyzed. All patients underwent endoscopic cyanoacrylate injection (ECI) for primary hemostasis. Modalities of secondary prophylaxis included endoscopic surveillance and beta-blockers (ECI and BBs), balloon-occluded retrograde transvenous obliteration (BRTO), and transjugular intrahepatic portosystemic shunt (TIPS). The incidence of rebleeding, mortality, and further decompensation among patients receiving ECI and BB was estimated and compared with a propensity score-matched (PSM) cohort of patients undergoing BRTO or TIPS.
Results
Three hundred and fifty-one patients were recruited. Of those 275 received ECI and BB, 54 underwent BRTO, and 22 underwent TIPS. The rebleeding rate at 1 year after ECI and BB was 19.2%, while the 1-year mortality and further decompensation rates were 19.7% and 27.8%, respectively. Rebleeding predominantly occurred from GV (76.1% of cases), with the cumulative 1-, 3-, and 5-year all-cause rebleeding rate among patients receiving ECI alone being 19.2%, 30%, and 35%, respectively. BRTO and TIPS significantly reduced all-cause rebleeding, but were associated with similar rates of further decompensation and mortality compared to ECI and BB in the PSM cohort.
Conclusion
BRTO and TIPS significantly reduce all-cause rebleeding as compared to ECI and BB, but their impact on further decompensation and overall survival requires further evaluation in larger cohorts.
{"title":"Endovascular Interventions for the Secondary Prophylaxis of Gastric Varices Prevent Rebleeding but May Not Improve Overall Survival: A Real-world Cohort From Two Centers","authors":"Sagnik Biswas , Santhosh E. Kumar , Sanchita Gupta , Pegatraju K. Bharadwaj , Shekhar Swaroop , Santhosh B. KB , Anuradha Sharma , Arnav Aggarwal , Umang Arora , Sarthak Saxena , Amitkumar Chavan , Rajkumar Bayye , Samagra Agarwal , Deepak Gunjan , Rahul Kumar , Shyamkumar N. Keshava , Shivanand Gamanagatti , Ashish Goel , Shalimar","doi":"10.1016/j.jceh.2025.103416","DOIUrl":"10.1016/j.jceh.2025.103416","url":null,"abstract":"<div><h3>Background</h3><div>There is limited literature on the long-term outcomes of patients with cirrhosis following an index gastric variceal (GV) hemorrhage.</div></div><div><h3>Methods</h3><div>Patients with cirrhosis and hemorrhage from gastroesophageal varices type-2 (GOV-2) or isolated gastric varices type-1 (IGV-1) from two tertiary care centers over 8 years were retrospectively analyzed. All patients underwent endoscopic cyanoacrylate injection (ECI) for primary hemostasis. Modalities of secondary prophylaxis included endoscopic surveillance and beta-blockers (ECI and BBs), balloon-occluded retrograde transvenous obliteration (BRTO), and transjugular intrahepatic portosystemic shunt (TIPS). The incidence of rebleeding, mortality, and further decompensation among patients receiving ECI and BB was estimated and compared with a propensity score-matched (PSM) cohort of patients undergoing BRTO or TIPS.</div></div><div><h3>Results</h3><div>Three hundred and fifty-one patients were recruited. Of those 275 received ECI and BB, 54 underwent BRTO, and 22 underwent TIPS. The rebleeding rate at 1 year after ECI and BB was 19.2%, while the 1-year mortality and further decompensation rates were 19.7% and 27.8%, respectively. Rebleeding predominantly occurred from GV (76.1% of cases), with the cumulative 1-, 3-, and 5-year all-cause rebleeding rate among patients receiving ECI alone being 19.2%, 30%, and 35%, respectively. BRTO and TIPS significantly reduced all-cause rebleeding, but were associated with similar rates of further decompensation and mortality compared to ECI and BB in the PSM cohort.</div></div><div><h3>Conclusion</h3><div>BRTO and TIPS significantly reduce all-cause rebleeding as compared to ECI and BB, but their impact on further decompensation and overall survival requires further evaluation in larger cohorts.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103416"},"PeriodicalIF":3.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735931","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}
Pub Date : 2025-11-21DOI: 10.1016/j.jceh.2025.103417
Tim E. Middelburg , Bregje Mol , Carlos Ferreira , Tom Davis , Karin Horsthuis , Ynte S. de Boer , Adriaan J. van der Meer , Annemarie C. de Vries , Roy S. Dwarkasing , Johannes A. Bogaards , Aart J. Nederveen , Jaap Stoker , Cyriel Y. Ponsioen
Background and aims
Qualitative magnetic resonance cholangiopancreatography (MRCP) scoring models in primary sclerosing cholangitis (PSC) are hampered by interobserver variability and evidence for quantitative MRCP has so far been limited by cohort sizes, follow-up time and lack of validation. This study aimed to validate the prognostic value of quantitative MRCP metrics in PSC in a large multicentre cohort.
Method
Retrospective, cross-sectional, clinical and quantified MRCP data by MRCP+ were collected from a non-transplant and transplant centre and randomised (1:1 ratio) into a derivation and validation set. Transplant-free survival, a composite of liver transplantation and PSC-related mortality (excluding colorectal carcinoma), was the primary endpoint. Least absolute shrinkage and selection operator analysis with manual guidance was used to compose a risk classifier. Prognostic performance and risk stratification were expressed by C-statistic and hazard ratios (HRs), and were validated in the validation set.
Results
A total of 224 patients were included with a median 6.8 years (Q1,Q3: 4.5, 9.8) of follow-up from MRCP onwards. Analysis identified number of strictures, proportion of 3–5 mm diameter ducts, years from diagnosis to MRCP and centre type as prognostic. The derived risk classifier showed a C-statistic of 0.72 (95% confidence interval [CI]: 0.60–0.81) and stratified effectively, with high-risk patients having threefold higher HR than low-risk patients (HR, 3.2; 95% CI: 1.6–6.4; P = 0.001) in the validation set.
Conclusion
This study confirms the prognostic value of quantitative MRCP (number of strictures and proportion of 3–5 mm diameter ducts) on long-term transplant-free survival in PSC and warrants further study on incorporating quantitative MRCP metrics into existing prognostic risk models.
背景与目的原发性硬化性胆管炎（PSC）的定性磁共振胆管造影（MRCP）评分模型受到观察者间可变性的阻碍，定量MRCP的证据迄今为止受到队列规模、随访时间和缺乏验证的限制。本研究旨在通过一个大型多中心队列验证定量MRCP指标在PSC中的预后价值。方法通过MRCP+收集来自非移植中心和移植中心的回顾性、横断面、临床和量化MRCP数据，并随机（1:1比例）纳入推导和验证集。无移植生存期是肝移植和psc相关死亡率（不包括结肠直肠癌）的组合，是主要终点。最小绝对收缩和选择算子分析与人工指导组成风险分类器。预后表现和风险分层用c统计量和危险比（hr）表示，并在验证集中进行验证。结果共纳入224例患者，从MRCP开始的中位随访时间为6.8年（Q1,Q3: 4.5, 9.8）。分析确定了狭窄的数量，3-5毫米直径导管的比例，从诊断到MRCP的时间和中心类型作为预后因素。导出的风险分类器的c统计量为0.72(95%可信区间[CI]: 0.60-0.81)，分层有效，在验证集中，高危患者的HR比低危患者高3倍（HR为3.2;95% CI: 1.6-6.4; P = 0.001）。结论本研究证实了定量MRCP（狭窄数量和直径3-5 mm导管比例）对PSC长期无移植生存的预后价值，值得进一步研究将定量MRCP指标纳入现有的预后风险模型。
{"title":"Validation of Quantitative Magnetic Resonance Cholangiopancreatography Metrics in Prediction of Transplant-free Survival in Primary Sclerosing Cholangitis","authors":"Tim E. Middelburg , Bregje Mol , Carlos Ferreira , Tom Davis , Karin Horsthuis , Ynte S. de Boer , Adriaan J. van der Meer , Annemarie C. de Vries , Roy S. Dwarkasing , Johannes A. Bogaards , Aart J. Nederveen , Jaap Stoker , Cyriel Y. Ponsioen","doi":"10.1016/j.jceh.2025.103417","DOIUrl":"10.1016/j.jceh.2025.103417","url":null,"abstract":"<div><h3>Background and aims</h3><div>Qualitative magnetic resonance cholangiopancreatography (MRCP) scoring models in primary sclerosing cholangitis (PSC) are hampered by interobserver variability and evidence for quantitative MRCP has so far been limited by cohort sizes, follow-up time and lack of validation. This study aimed to validate the prognostic value of quantitative MRCP metrics in PSC in a large multicentre cohort.</div></div><div><h3>Method</h3><div>Retrospective, cross-sectional, clinical and quantified MRCP data by MRCP+ were collected from a non-transplant and transplant centre and randomised (1:1 ratio) into a derivation and validation set. Transplant-free survival, a composite of liver transplantation and PSC-related mortality (excluding colorectal carcinoma), was the primary endpoint. Least absolute shrinkage and selection operator analysis with manual guidance was used to compose a risk classifier. Prognostic performance and risk stratification were expressed by C-statistic and hazard ratios (HRs), and were validated in the validation set.</div></div><div><h3>Results</h3><div>A total of 224 patients were included with a median 6.8 years (Q1,Q3: 4.5, 9.8) of follow-up from MRCP onwards. Analysis identified number of strictures, proportion of 3–5 mm diameter ducts, years from diagnosis to MRCP and centre type as prognostic. The derived risk classifier showed a C-statistic of 0.72 (95% confidence interval [CI]: 0.60–0.81) and stratified effectively, with high-risk patients having threefold higher HR than low-risk patients (HR, 3.2; 95% CI: 1.6–6.4; <em>P</em> = 0.001) in the validation set.</div></div><div><h3>Conclusion</h3><div>This study confirms the prognostic value of quantitative MRCP (number of strictures and proportion of 3–5 mm diameter ducts) on long-term transplant-free survival in PSC and warrants further study on incorporating quantitative MRCP metrics into existing prognostic risk models.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 1","pages":"Article 103417"},"PeriodicalIF":3.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733058","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}
Pub Date : 2025-11-20DOI: 10.1016/j.jceh.2025.103415
Ajay K. Mishra , Shreya Pandey , Shaiphali Sharma , Surender Singh , Neeraj Sinha , Sumit Rungta , Anand V. Kulkarni , Amit Goel
Background/Aims
Granulocyte colony-stimulating factor (GCSF) has been used to treat severe alcohol-associated hepatitis (SAH) in different combinations and dosages with variable outcomes. We aimed to evaluate the efficacy of GCSF for the treatment of severe alcoholic hepatitis (AH).
Methods
We conducted a systematic review and meta-analysis of studies comparing GCSF versus standard medical therapy (SMT) to treat patients with severe AH.
Results
Eight studies were selected after screening 875 studies with a total of 1241 participants enrolled including 376 female participants. Overall 90-day survival rates were 85.35% and 61.8% in GCSF and SMT groups, respectively. GCSF therapy was associated with a significant increase in 90-day survival, with an odds ratio (OR) of 3.61 (95% confidence interval [CI]: 2.6–5.00) and I2 = 7.2%. The 28-day survival between the GCSF therapy and SMT groups were comparable (83.91% and 72.9%, respectively), with an OR of 1.9 (95% CI: 0.87–4.1) and I2 = 43.2%. In patients who received anti-inflammatory therapies in combination with GCSF, overall survival was 83.89% and 81.35% in the combination group and 71.84% and 51.45% in the SMT group on days 28 and 90, respectively, with an overall pooled OR of 4.86 (95% CI: 1.63–14.46) at day 90 and 2.53 (95% CI, 1.07–6.03) on day 28 associated low heterogeneity (I2 = 20.5% and 24.2%, respectively). The overall rate of infection on day 90 was 20.1% in the GCSF arm and 27.22% in the control arm, with pooled ORs of 0.36 (95% CI: 0.18–0.691). The overall variceal bleeding rates were 5.6% in the GCSF and 14.07% in the control group on day 90. GCSF therapy is associated with a decreased risk of variceal bleeding compared with controls, with an OR of 0.41 (95% CI: 0.25–0.67).
Conclusion
GCSF therapy is associated with higher survival and lower adverse events in SAH. Combining GCSF with anti-inflammatory therapies can further improve 28- and 90-day survival.
{"title":"Granulocyte Colony Stimulating Factor and Its Combinations With Anti-inflammatory Therapies in Severe Alcoholic Hepatitis: A Systematic Review and Meta-analysis","authors":"Ajay K. Mishra , Shreya Pandey , Shaiphali Sharma , Surender Singh , Neeraj Sinha , Sumit Rungta , Anand V. Kulkarni , Amit Goel","doi":"10.1016/j.jceh.2025.103415","DOIUrl":"10.1016/j.jceh.2025.103415","url":null,"abstract":"<div><h3>Background/Aims</h3><div>Granulocyte colony-stimulating factor (GCSF) has been used to treat severe alcohol-associated hepatitis (SAH) in different combinations and dosages with variable outcomes. We aimed to evaluate the efficacy of GCSF for the treatment of severe alcoholic hepatitis (AH).</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of studies comparing GCSF versus standard medical therapy (SMT) to treat patients with severe AH.</div></div><div><h3>Results</h3><div>Eight studies were selected after screening 875 studies with a total of 1241 participants enrolled including 376 female participants. Overall 90-day survival rates were 85.35% and 61.8% in GCSF and SMT groups, respectively. GCSF therapy was associated with a significant increase in 90-day survival, with an odds ratio (OR) of 3.61 (95% confidence interval [CI]: 2.6–5.00) and I<sup>2</sup> = 7.2%. The 28-day survival between the GCSF therapy and SMT groups were comparable (83.91% and 72.9%, respectively), with an OR of 1.9 (95% CI: 0.87–4.1) and I<sup>2</sup> = 43.2%. In patients who received anti-inflammatory therapies in combination with GCSF, overall survival was 83.89% and 81.35% in the combination group and 71.84% and 51.45% in the SMT group on days 28 and 90, respectively, with an overall pooled OR of 4.86 (95% CI: 1.63–14.46) at day 90 and 2.53 (95% CI, 1.07–6.03) on day 28 associated low heterogeneity (I<sup>2</sup> = 20.5% and 24.2%, respectively). The overall rate of infection on day 90 was 20.1% in the GCSF arm and 27.22% in the control arm, with pooled ORs of 0.36 (95% CI: 0.18–0.691). The overall variceal bleeding rates were 5.6% in the GCSF and 14.07% in the control group on day 90. GCSF therapy is associated with a decreased risk of variceal bleeding compared with controls, with an OR of 0.41 (95% CI: 0.25–0.67).</div></div><div><h3>Conclusion</h3><div>GCSF therapy is associated with higher survival and lower adverse events in SAH. Combining GCSF with anti-inflammatory therapies can further improve 28- and 90-day survival.</div></div>","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"16 2","pages":"Article 103415"},"PeriodicalIF":3.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837967","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}
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