Rohan Karkra, Mahinaz Mohsen, Joshua E Pagán-Busigó, Ethan Shamsian, Michael Bebawy, Steven Rella, Zaid Tafesh, Paul Gaglio
{"title":"Comparative Efficacy of Bulevirtide, Interferons, and Nucleos(t)ide Analogs for Chronic Hepatitis Delta: A Systematic Review and Network Meta-Analysis.","authors":"Rohan Karkra, Mahinaz Mohsen, Joshua E Pagán-Busigó, Ethan Shamsian, Michael Bebawy, Steven Rella, Zaid Tafesh, Paul Gaglio","doi":"10.1155/ijh/6325996","DOIUrl":"10.1155/ijh/6325996","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis D virus (HDV) continues to be a global health concern, and the infection remains challenging to treat. Over the past few decades, pegylated interferons, typically in combination with therapy for hepatitis B, have become the standard of care, with considerable side effects and frequently unsatisfactory results. Several new therapies are emerging, including bulevirtide and lonafarnib. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of bulevirtide, interferons, and nucleos(t)ide analogs, alone or in combination, for the treatment of chronic hepatitis D.</p><p><strong>Methods: </strong>PubMed, Embase, and Cochrane databases were searched for randomized controlled trials and nonrandomized interventional studies assessing HDV RNA suppression, biochemical response, combined response, and histological improvement with various therapies. NMA was performed using a frequentist random-effects model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and forest plots were generated.</p><p><strong>Results: </strong>Thirteen studies (<i>n</i> = 922) were included, studying nine possible treatment arms. At the end of treatment, 31.8% achieved a virological response. Bulevirtide monotherapy (OR 38.63, <i>p</i> < 0.05) and combinations with NA (OR 69.36, <i>p</i> < 0.05) and peginterferon alpha (OR 260.08, <i>p</i> < 0.05) significantly suppressed HDV RNA, with the bulevirtide-peginterferon alpha combination having the highest HDV RNA suppression. At ≥ 24-week follow-up, no regimen maintained significant HDV RNA suppression. Biochemical response was achieved in 42.7% at the end of treatment; however, no group reached statistical significance versus control, though bulevirtide and its combination with peginterferon alpha outperformed peginterferon alpha alone. Combined response was highest with bulevirtide-peginterferon alpha (OR 112.69, <i>p</i> < 0.05), followed by bulevirtide monotherapy. Histological response (five studies, <i>n</i> = 183) was not statistically significant with any intervention compared with control.</p><p><strong>Conclusion: </strong>Bulevirtide and peginterferon alpha combination therapy may offer the most promising treatment for chronic hepatitis D. More studies are needed to assess the efficacy of this regimen and establish the optimum dose and duration of treatment.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2026 ","pages":"6325996"},"PeriodicalIF":1.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147785164","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":"Injecting Drug Use History and Younger Age Worsen Adherence to Scheduled Hospital Visits in Glecaprevir and Pibrentasvir Therapy for Chronic Hepatitis C.","authors":"Seiichi Tawara, Asuka Watanabe, Junya Yamaguchi, Mai Omi, Tetsuro Miyazaki, Haruka Taguchi, Ryosuke Kiyota, Takuo Yamai, Shoichiro Kawai, Takuya Inoue, Takayuki Yakushijin","doi":"10.1155/ijh/5053151","DOIUrl":"10.1155/ijh/5053151","url":null,"abstract":"<p><strong>Aim: </strong>The use of direct-acting antivirals (DAAs) against the Hepatitis C virus (HCV) has rapidly expanded since their introduction. However, some patients with HCV infection may still not receive appropriate medical care. This study analyzed the characteristics and adherence of the population receiving therapy with two later-generation DAAs, glecaprevir (GLE) and pibrentasvir (PIB), to investigate the clinical challenges associated with HCV treatment.</p><p><strong>Methods: </strong>A total of 141 consecutive patients who underwent GLE/PIB therapy for chronic HCV infection between December 2017 and June 2021 were enrolled. Patient backgrounds and adherence were retrospectively analyzed.</p><p><strong>Results: </strong>Median patient age was 61 years. Eighteen patients had a history of injecting drug use (IDU), accounting for 13% of the sample. At the end of treatment, three patients (2.1%) self-discontinued hospital visits. The number of patients who self-discontinued hospital visits gradually increased over time to 9 (6.4%) at 4 weeks after treatment, 16 (11.3%) at 12 weeks after treatment, and 24 (17.0%) at 24 weeks after treatment. The sustained viral response rate after 12 weeks, excluding patients who self-discontinued hospital visits, was 96.8% (121/125). In a multivariate analysis, age < 60 years and a history of IDU were significant factors associated with the self-discontinuation of hospital visits. The hazard ratio (HR) for those younger than 60 years old was 3.17 (<i>p</i> = 0.012), whereas the HR for those with a history of IDU was 2.41 (<i>p</i> = 0.036).</p><p><strong>Conclusions: </strong>History of IDU and younger age were significantly associated with poor adherence to GLE/PIB treatment.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2026 ","pages":"5053151"},"PeriodicalIF":1.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031377","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":"Global Bivariate Meta-Analysis of FIB-4 Cut-Offs to Rule Out Advanced Fibrosis in MASLD.","authors":"Anuradha Ghosal, Samit Ghosal","doi":"10.1155/ijh/9419416","DOIUrl":"10.1155/ijh/9419416","url":null,"abstract":"<p><strong>Background: </strong>The fibrosis-4 (FIB-4) index, a non-invasive marker, evaluates advanced fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD), but the variability in its performance across different populations remains unclear.</p><p><strong>Methods: </strong>We conducted a systematic review and bivariate meta-analysis of 14 studies (<i>N</i> = 5521) with 2 × 2 contingency data for FIB-4 at thresholds < 1.0 and < 1.3, compared with liver biopsy or transient elastography (TE). The Reitsma model (R v4.4.3) estimated pooled sensitivity and specificity. Subgroup analyses assessed region (India vs. global) and reference standard effects, with heterogeneity and publication bias (Deeks' test) evaluated.</p><p><strong>Results: </strong>Pooled sensitivity was 0.73 (95% CI: 0.69-0.77), and specificity was 0.69 (95% CI: 0.61-0.76) at < 1.3. The < 1.0 threshold demonstrated higher specificity (0.83, 95% CI: 0.75-0.89) but lower sensitivity (0.63, 95% CI: 0.58-0.68). Indian cohorts (<i>n</i> = 3) exhibited higher specificity (0.83) than the global estimate (0.66) at < 1.3, whereas sensitivity remained similar.</p><p><strong>Conclusion: </strong>FIB-4 below 1.3 is a useful initial tool for ruling out advanced fibrosis in MASLD, with potential regional variations in specificity. Larger studies are needed to confirm cut-offs, supporting tailored guidelines with sequential testing.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2026 ","pages":"9419416"},"PeriodicalIF":1.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991141","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}
Kelly Tin Long Chan, Oi Ling Chan, Yin Yee Lam, Siu Wing Lawrence Lai
{"title":"Noninvasive Assessment of Prehepatic Portal Hypertension: Pilot Data on Spleen Stiffness in Portal Vein Thrombosis.","authors":"Kelly Tin Long Chan, Oi Ling Chan, Yin Yee Lam, Siu Wing Lawrence Lai","doi":"10.1155/ijh/5531253","DOIUrl":"10.1155/ijh/5531253","url":null,"abstract":"<p><strong>Background: </strong>Portal vein thrombosis (PVT) is a vascular liver disorder defined by a thrombus in the portal vein or its intrahepatic branches. Computed tomography (CT) and upper endoscopy are, respectively, used to monitor for PVT progression and portal hypertensive complications. A noninvasive modality-spleen stiffness (SS)-has shown promise in identifying clinically significant portal hypertension (CSPH) in cirrhosis. It is unknown whether SS demonstrates any correlation with PVT, a condition associated with prehepatic portal hypertension.</p><p><strong>Aims: </strong>The primary aim was to determine the association between SS and the presence of PVT. The secondary aim was to evaluate the association between SS and portal hypertension-related complications among patients with PVT.</p><p><strong>Methods: </strong>This cross-sectional study was undertaken at two regional hospitals in Hong Kong from January 2023 to March 2024. Patients were identified via CT and allocated to either the PVT or non-PVT group. Chronic liver disease was an exclusion criterion for both groups. SS was assessed using transient elastography within 3 months of PVT diagnosis. Demographic, clinical, and laboratory data were collected within 3 months of PVT diagnosis.</p><p><strong>Results: </strong>A total of 46 patients with PVT (median age, 69 years; interquartile range [IQR], 62-78; 74% male) were compared with 45 controls. Both SS and liver stiffness (LS) were significantly higher in the PVT cohort than in controls (SS: 27.9 [IQR, 19.5-42.8] vs. 16.9 kPa [IQR, 13.6-21.2], <i>p</i> < 0.001; LS: 6.0 [IQR, 4.8-8.6] vs. 4.6 kPa [IQR, 3.7-5.9], <i>p</i> < 0.001). Among patients with PVT, those with portal hypertension-related complications demonstrated markedly elevated SS compared with those without complications (77.7 [IQR, 47.2-85.0] vs. 24.4 kPa [IQR, 18.9-37.1], <i>p</i> < 0.001). Furthermore, SS values increased in proportion to the anatomical extent of PVT involvement.</p><p><strong>Conclusion: </strong>Elevated SS was observed in patients with PVT, particularly in those with PVT-induced portal hypertension. Large-scale, prospective studies are warranted to confirm the association between SS and PVT and to establish its potential role in noncirrhotic portal hypertension.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"5531253"},"PeriodicalIF":1.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12752816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879254","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}
Qiang Yu, Liangning Hu, Chenfei Tan, Min Gao, Zhenzhen Wen
{"title":"PFKL Inhibition by DT-13: A Novel Approach to Combat Hepatocellular Carcinoma.","authors":"Qiang Yu, Liangning Hu, Chenfei Tan, Min Gao, Zhenzhen Wen","doi":"10.1155/ijh/5211859","DOIUrl":"10.1155/ijh/5211859","url":null,"abstract":"<p><p>Aerobic glycolysis modulates proliferation, apoptosis, immune evasion, and targeted drug resistance in hepatocellular carcinoma (HCC) patients. Therefore, inhibiting aerobic glycolysis could represent a novel chemotherapeutic strategy for HCC. The effects of <i>Liriope muscari</i> Baily's Saponin C (DT-13), a novel compound isolated from the traditional Chinese medicine <i>Liriope muscari</i> (Decne) Baily, on HCC and its underlying mechanism remain unknown. This study revealed that DT-13 induces apoptosis and inhibits the in vivo and in vitro proliferation of HCC cells. Furthermore, DT-13 significantly reduced glucose consumption and lactate production. Moreover, it was observed that DT-13 could inhibit Phosphofructokinase-1 liver (PFKL) type via c-myc signaling to modulate the aerobic glycolysis, proliferation, and apoptosis of HCC. Moreover, DT-13 improved the anticancer effects of sorafenib in HCC. In summary, this study provided evidence for the potential application of DT-13 in HCC treatment.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"5211859"},"PeriodicalIF":1.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12752837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879260","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}
Marrium Sultan Dar, Tooba Fatima, Syeda Dua Azhar, Zuhaa Rehman, Muhammad Affan, Yusra Muhammad Saleem, Saqib Ali, Fabiha Athar, Samra Ishaq, Noor Ul Ain, Jawad Zahid, Aimen Waqar Khan, Haziq Ovais, Tagwa Kalool Fadlalla Ahmad, Khabab Abbasher Hussien Mohamed Ahmed, Hareesha Rishab Bharadwaj
{"title":"Randomized Controlled Trial Evidence on Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.","authors":"Marrium Sultan Dar, Tooba Fatima, Syeda Dua Azhar, Zuhaa Rehman, Muhammad Affan, Yusra Muhammad Saleem, Saqib Ali, Fabiha Athar, Samra Ishaq, Noor Ul Ain, Jawad Zahid, Aimen Waqar Khan, Haziq Ovais, Tagwa Kalool Fadlalla Ahmad, Khabab Abbasher Hussien Mohamed Ahmed, Hareesha Rishab Bharadwaj","doi":"10.1155/ijh/8870546","DOIUrl":"10.1155/ijh/8870546","url":null,"abstract":"<p><strong>Purpose: </strong>Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic acid (OCA) serves as a second-line option because of moderate UDCA nonresponsiveness and cirrhosis-related concerns. Additional therapies are necessary because of recent warnings regarding OCA usage in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC.</p><p><strong>Methods: </strong>We searched PubMed, Google Scholar, and the Cochrane Library until October 2023. We included all randomized controlled trials (RCTs) that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was change in alkaline phosphatase (ALP) levels. In contrast, the secondary outcomes were changes in gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride levels, and pruritis. We used a random-effects model to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% CI.</p><p><strong>Results: </strong>A total of eight RCTs (<i>n</i> = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared with placebo for change in ALP level (SMD = -2.81, 95%CI = -4.10 to - 1.51; <i>p</i> < 0.0001, I<sup>2</sup> = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; <i>p</i> = 0.002, I<sup>2</sup> = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; <i>p</i> = 0.006, I<sup>2</sup> = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; <i>p</i> = 0.003, I<sup>2</sup> = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; <i>p</i> = 0.07, I<sup>2</sup> = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; <i>p</i> = 0.99, I<sup>2</sup> = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; <i>p</i> = 0.60, I<sup>2</sup> = 34%).</p><p><strong>Conclusion: </strong>Our study found a superior efficacy of PPAR agonists compared with placebo for change in ALP, GGT, TBil, and Tg levels, highlighting the potentially beneficial effect of PPAR agonists on liver health.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"8870546"},"PeriodicalIF":1.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726850","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":"Association Between Subclinical Hypothyroidism and MASLD: A Systematic Review and Meta-Analysis.","authors":"Gedion Yilma Amdetsion, Chun-Wei Pan, Hiwot Tebeje, Abhin Sapkota, Shreyas Nandyal, Vikram Kotwal","doi":"10.1155/ijh/8133686","DOIUrl":"10.1155/ijh/8133686","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder that can progress to cirrhosis and hepatocellular carcinoma. Although overt hypothyroidism has been identified as a MASLD risk factor, the impact of subclinical hypothyroidism (SCH), which affects approximately 4.6% of US adults, remains unclear. We conducted a systematic review and meta-analysis to determine whether SCH is independently associated with MASLD and to inform targeted screening recommendations.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Cochrane, ClinicalTrials.gov, and Web of Science up to June 2025 for studies evaluating the association between SCH and MASLD. Random-effects meta-analyses were performed on eligible cross-sectional and longitudinal studies.</p><p><strong>Results: </strong>We screened 537 records and ultimately included 10 high-quality studies with 71,332 participants. Overall, 22.3% had MASLD and 7.7% had SCH. In cross-sectional analyses (<i>n</i> = 39,814), SCH was linked to 46% higher odds of MASLD (pooled OR = 1.46, 95% CI 1.23-1.73; <i>I</i> <sup>2</sup> = 36%). Across four longitudinal cohorts (<i>n</i> = 31,518), SCH raised the risk of incident MASLD by 59% (pooled HR = 1.59, 95% CI 1.05-2.40). Limiting the analysis to prospective studies strengthened the association (HR = 1.90, 95% CI 1.50-2.39) and eliminated heterogeneity (<i>I</i> <sup>2</sup> = 0).</p><p><strong>Conclusions: </strong>This meta-analysis provides evidence that SCH is associated with both higher odds of prevalent MASLD and increased risk of incident MASLD. Clinicians should consider routine screening for MASLD in patients with SCH and vice versa.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"8133686"},"PeriodicalIF":1.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12681400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702312","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}
Eyad Makkawy, Shaden Mohammed Alamro, Safiya Ibn Awadh, Reem Basalasil, Ziyad Alkhelaiwi, Bassam Al-Mutairi, Fatimah Rebh
{"title":"Impact of Elevated Liver Enzymes on the Severity of Clinical Course of COVID-19: A Retrospective Study From Saudi Arabia.","authors":"Eyad Makkawy, Shaden Mohammed Alamro, Safiya Ibn Awadh, Reem Basalasil, Ziyad Alkhelaiwi, Bassam Al-Mutairi, Fatimah Rebh","doi":"10.1155/ijh/7385050","DOIUrl":"10.1155/ijh/7385050","url":null,"abstract":"<p><strong>Background: </strong>According to recent research, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause liver injury, which may be linked to a poorer prognosis. In this retrospective study, we evaluated the incidence of high liver enzyme levels in patients with COVID-19 and their correlation with the severity and prognosis of clinical outcomes.</p><p><strong>Methods: </strong>A retrospective cohort study was performed from March 2020 to October 2020 at Prince Mohammed Bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Demographic information of COVID-19 patients as well as data on clinical features and laboratory parameters were collected. Pearson's correlation (<i>r</i>) test was used to assess the correlation between elevated liver enzymes and COVID-19 severity. The multivariate logistic binary regression analysis was used to identify the predictors of elevated liver enzyme levels and mortality among patients with COVID-19.</p><p><strong>Results: </strong>This cohort included 1033 patients, 73% of whom were male, with a mean age of 49.9 years. Elevated liver enzymes were observed in 52.7% of patients, most commonly with a hepatitis pattern (63.1%). Elevated levels of hemoglobin, creatine kinase-myocardial band, and C-reactive protein, as well as pneumoniae, the requirement of an intensive care unit, comorbidities, and the use of paracetamol, <i>β</i>-lactamase, and steroids were significant predictors of elevated liver enzymes (<i>p</i> < 0.05). Interestingly, Saudi patients (<i>p</i> = 0.019) were found to be a significant protective predictor of elevated liver enzymes. Our findings revealed that elevated liver enzyme levels were significantly correlated with the severity of COVID-19 (<i>p</i> < 0.05) in terms of qSOFA score. Moreover, older age, diabetes, qSOFA score, and elevated hepatitis enzymes were associated with mortality (<i>p</i> = 0.043).</p><p><strong>Conclusions: </strong>Elevated liver enzyme levels were common in patients with COVID-19 and were associated with the severity and prognosis of clinical outcomes.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"7385050"},"PeriodicalIF":1.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679101","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":"Impact of Age on Mortality and Decompensation Events in Patients With Liver Cirrhosis: A Multicenter, Propensity Score Matched Study.","authors":"Muhammad Shabbir, Miguel Salazar, Zeid Kayali","doi":"10.1155/ijh/8852224","DOIUrl":"10.1155/ijh/8852224","url":null,"abstract":"<p><strong>Background: </strong>The incidence of cirrhosis is increasing in the older population. Limited data are available on the disease progression and mortality in the older population with cirrhosis. This study is aimed at evaluating the impact of age at diagnosis on all-cause mortality and decompensation events in patients with liver cirrhosis.</p><p><strong>Methods: </strong>This is a retrospective cohort study utilizing TriNetX. ICD codes were used to identify individuals with the diagnosis of liver cirrhosis between the ages of 20 and 80. Patients with the diagnosis of congestive heart failure (CHF), end-stage renal disease (ESRD), chronic kidney disease (CKD) Stage IV and V, human immunodeficiency virus (HIV), malignant neoplasm, and psychoactive substance abuse were excluded from the analyses. Patients were divided into two cohorts: Cohort 1 included individuals with the diagnosis of liver cirrhosis between the ages of 51 and 80, and Cohort 2 included individuals with the diagnosis between the ages of 20 and 50. Statistical analyses were conducted using TriNetX Live. A 1:1 propensity score matching was performed for variables including race, gender, ethnicity, comorbidities, laboratory values for MELD 3.0, and etiology of liver cirrhosis. There were 70,983 patients in each cohort after matching. The primary outcome was all-cause mortality, and the composite outcome of decompensation events at 5- and 10-year intervals from the age of diagnosis of liver cirrhosis. Secondary outcomes included the risk of decompensation events, all-cause hospitalization at 5-year intervals, and a subgroup analysis of all-cause mortality and decompensation events among males and females.</p><p><strong>Results: </strong>Older age at diagnosis of liver cirrhosis was associated with increased all-cause mortality at 5 years (aOR 1.378, 95% CI: 1.335-1.422; <i>p</i> < 0.001) and 10 years (aOR 1.418, 95% CI: 1.376-1.462; <i>p</i> < 0.001). These patients also demonstrated an increased risk of decompensation events at 5 years (aOR 1.236, 95% CI: 1.199, 1.275; <i>p</i> < 0.001) and at a 10-year interval (aOR 1.266, 95% CI: 1.229, 1.305; <i>p</i> < 0.001). At 5-year intervals, these patients (Cohort 1) were found to have an increased risk of variceal bleeding (aOR 1.309, 95% CI: 1.258-1.361; <i>p</i> < 0.001), ascites (aOR 1.114, 95% CI: 1.052-1.180; <i>p</i> < 0.001), hepatic encephalopathy (aOR 1.1, 95% CI: 1.026-1.180; <i>p</i> < 0.001), hepatopulmonary syndrome (aOR 1.45, 95% CI: 0.820-2.564; <i>p</i> = 0.101), and hepatocellular carcinoma (aOR 2.924, 95% CI: 2.477-3.453, <i>p</i> < 0.001). Conversely, in younger patients, there were increased odds of developing spontaneous bacterial peritonitis (SBP) (aOR 0.848, 95% CI: 0.720-0.998, <i>p</i> = 0.02) and hepatorenal syndrome (HRS) (aOR 0.753, 95% CI: 0.651-0.871, <i>p</i> < 0.01). The differences were persistent in a subgroup analysis among males (mortality, aOR 1.37, 95% CI: 1.319, 1.424; <i>p</i> < 0.001) and","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"8852224"},"PeriodicalIF":1.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662355","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}
Debasree Bishnu, Suman Santra, Swagata Purkait, Amal Santra
{"title":"Unraveling the Role of CYP2E1 in Antitubercular Drug-Induced Hepatotoxicity: From Molecular Mechanisms to Clinical Implications.","authors":"Debasree Bishnu, Suman Santra, Swagata Purkait, Amal Santra","doi":"10.1155/ijh/9980298","DOIUrl":"10.1155/ijh/9980298","url":null,"abstract":"<p><p>Antitubercular (AT) drugs, particularly isoniazid (INH), rifampicin (RIF), pyrazinamide (PYZ), and ethambutol (EMB), are the cornerstone of tuberculosis (TB) treatment. However, their use is often limited by the risk of hepatotoxicity, a potentially severe side effect. Among the factors implicated in drug-induced liver injury, cytochrome P450 2E1 (CYP2E1) is emerging as a key enzyme in the pathogenesis of hepatotoxicity. CYP2E1 is involved in the oxidative metabolism of many xenobiotics, including AT drugs, and is known to produce reactive oxygen species (ROS) during the metabolism process, which can lead to cellular damage. This review investigates the potential role of CYP2E1 in the mechanisms behind AT drug-induced hepatotoxicity and explores the biochemical and molecular pathways through which CYP2E1 might contribute to liver injury. Genetic polymorphisms in the CYP2E1 gene, which affect its activity, may also play a role in individual susceptibility to AT drug-induced hepatotoxicity. This review also deals with how multifactorial interactions including genetic polymorphisms in CYP2E1, N-acetyl transferase 2 (NAT2), and glutathione-S-transferase (GST), as well as factors such as drug-drug interactions, nutritional status, coexisting infections (e.g., hepatitis B/C), and alcohol consumption collectively modulate individual susceptibility to AT drug-induced hepatotoxicity. By elucidating the role of CYP2E1 in AT drug-induced hepatotoxicity, this review provides a foundation for future therapeutic strategies, including the development of safer drug formulations or adjunct therapies targeting CYP2E1 to mitigate hepatotoxicity.</p>","PeriodicalId":46297,"journal":{"name":"International Journal of Hepatology","volume":"2025 ","pages":"9980298"},"PeriodicalIF":1.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12660623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649541","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}