International Journal of Hepatology最新文献

Purpose: 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.

Methods: 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.

Results: A total of eight RCTs (n = 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; p < 0.0001, I² = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; p = 0.002, I² = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; p = 0.006, I² = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; p = 0.003, I² = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; p = 0.07, I² = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; p = 0.99, I² = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; p = 0.60, I² = 34%).

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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 (n = 39,814), SCH was linked to 46% higher odds of MASLD (pooled OR = 1.46, 95% CI 1.23-1.73; I ² = 36%). Across four longitudinal cohorts (n = 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 ² = 0).

Conclusions: 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.

Background: 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.

Methods: 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 (r) 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.

Results: 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, β-lactamase, and steroids were significant predictors of elevated liver enzymes (p < 0.05). Interestingly, Saudi patients (p = 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 (p < 0.05) in terms of qSOFA score. Moreover, older age, diabetes, qSOFA score, and elevated hepatitis enzymes were associated with mortality (p = 0.043).

Conclusions: Elevated liver enzyme levels were common in patients with COVID-19 and were associated with the severity and prognosis of clinical outcomes.

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.

Background: Shock is a rare life-threatening complication in patients with adult-onset Still's disease (AOSD) complicated by macrophage activation syndrome (MAS). This study aims to summarize the clinical characteristics and prognosis of this condition.

Methods: We performed a retrospective study of 14 patients hospitalized from January 2017 to December 2023 who experienced shock secondary to AOSD complicated by MAS.

Results: Among the 14 patients, 11 presented with a progressive rash, and 10 exhibited a remittent fever prior to shock onset. Compared to levels at admission, serum ferritin (SF), lactate dehydrogenase (LDH), and procalcitonin levels were significantly elevated, while serum albumin (ALB) levels were significantly decreased, both at the time of MAS diagnosis and at the onset of shock. Shock resolved in nine patients, and five died. All the improved patients were treated with high-dose glucocorticoids (equivalent prednisolone dose ≥ 1 mg/kg/day) prior to MAS diagnosis, and received glucocorticoid pulse therapy. Among them, five (55.6%) received combination therapy with low-dose etoposide and cyclosporine, one (11.1%) received etoposide alone, one (11.1%) received a combination of cyclosporine and tocilizumab, and two (22.2%) receive no additional immunosuppressive therapy. Of the five patients who died, four (80%) received glucocorticoids therapy (two before MAS diagnosis), and only two received a combination of cyclosporine. None of the deceased patients received tocilizumab or etoposide. Compared to patients who died, the patients who improved had significantly higher rates of early glucocorticoid therapy (100% vs. 40%, p = 0.027) and etoposide use (66.7% vs. 0%, p = 0.028).

Conclusion: Shock is a life-threatening condition secondary to AOSD with MAS. The early combined use of high-dose glucocorticoids and etoposide may be key to improving outcomes in this critical condition.

Background: The objective was to develop consensus on minimal screening criteria for Wilson disease (WD) diagnosis in US gastroenterology and neurology settings for implementation in clinical practice to support the timely diagnosis of WD.

Methods: A modified Delphi panel with three rounds was conducted. The first round survey was developed with input from a steering committee of four clinical experts in WD who set the analysis rules (consensus: ≥ 80%). Other US gastroenterologists/hepatologists or neurologists with experience treating WD were recruited using purposive sampling, and 32 were invited to participate.

Results: Eleven panelists completed the three rounds. Consensus was reached for 94/126 (74.6%) statements. All panelists agreed that hepatomegaly, splenomegaly, or stigmata of liver disease are suggestive of WD in patients with a neuropsychiatric manifestation; a neurologic exam, 24-h urine copper, ceruloplasmin, and Kayser-Fleischer (KF) ring examination should be performed; and liver biopsy and liver copper determination can be a useful final stage to confirm WD diagnosis. Panelists agreed that noninvasive testing should be performed prior to invasive testing and that the absence of KF rings does not exclude a diagnosis of WD. Panelists agreed that it is important to collaborate in a multidisciplinary team.

Conclusions: This study identified minimal criteria to raise suspicion of WD, minimal tests to confirm or rule out a WD diagnosis, and areas with poor consensus to be explored in future research. These results can complement clinical practice guidance and support cross-specialty collaboration.

Aim: Alcoholic liver disease (ALD) is a major global health burden, with alcoholic hepatitis (AH) and severe alcoholic hepatitis (SAH) contributing significantly to mortality. Inflammation plays a central role in disease progression, and various anti-inflammatory therapies, particularly corticosteroids, have been employed to improve survival. However, clinical outcomes across different treatments vary. This systematic review is aimed at evaluating the effectiveness of anti-inflammatory pharmacological therapies compared to corticosteroids in improving short-term survival at 1, 3, and 6 months and to assess the incidence of adverse events in patients with ALD.

Methods: The review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, and Clarivate Web of Science using MeSH terms. Inclusion criteria consisted of full-text, open-access, English articles (2014-2024) that reported survival outcomes and adverse events in patients with ALD treated with corticosteroids versus alternative or adjunctive anti-inflammatory therapies. Studies lacking a corticosteroid comparator were excluded.

Results: Nine randomized controlled trials (RCTs) involving patients with AH and SAH were included. The interventions compared to corticosteroids included pentoxifylline, anakinra, metadoxine, S-adenosylmethionine (SAMe), granulocyte colony-stimulating factor (G-CSF), rifaximin, and fecal microbiota transplantation (FMT) as monotherapies or combination regimens. Among anti-inflammatory therapies, combination therapy with corticosteroids and metadoxine significantly improves 3- and 6-month survival rates in patients with ALD. Similarly, corticosteroids combined with SAMe demonstrate efficacy in enhancing 1- and 6-month survival rates. Notably, the metadoxine-based combination regimen exhibited a superior safety profile, with fewer adverse events compared to other anti-inflammatory therapies evaluated in this review.

Conclusions: Even though corticosteroids remain the current standard of care for severe AH, this review suggests that certain combination therapies, particularly those involving metadoxine or SAMe, may offer some survival benefits. FMT also shows promise by potentially improving survival while maintaining a favorable safety profile. Among these, the metadoxine-based regimen has been explored as a promising therapeutic strategy in some contexts. However, these findings must be interpreted with caution. The evidence is limited by significant study heterogeneity and a lack of high-quality RCTs. These limitations underscore the critical need for well-powered, rigorous RCTs with standardized survival and safety outcomes.

Introduction: The issue of fatty liver disease is becoming more widely acknowledged as a global health concern. This disorder manifests as inflammation brought on by varied degrees of fat buildup in the liver tissue. Since studies have shown that fatty liver is a major factor affecting the prognosis of patients with chronic hepatitis, the coexistence of viral hepatitis and fatty liver is noteworthy. Transient elastography is a useful technique for identifying and measuring the degree of steatosis. The liver stiffness measurement (LSM) index might be a good substitute for these patients if it shows a high diagnostic value in identifying hepatic steatosis.

Methods: This pilot study presents an analytical cross-sectional analysis of 53 hepatitis B patients (26 men and 27 women) who sought care at Aria Hospital in Ahvaz, Iran, between April 2023 and November 2024. Participants were divided into two groups: 34 patients in the treatment group and 19 patients in the nontreatment group. The subjects' prevalence of hepatic fibrosis was evaluated using transient elastography and the LSM index. Further comparisons between treatment-receiving and nonreceiving patients were conducted using LSM.

Results: The prevalence of steatosis was found to be 25% in the untreated group and 26.7% in the treatment group. In the treatment group, the incidence of fibrosis was 58.8%, while in the untreated group, it was 57.9%. In both the treatment-treated and nontreated groups of hepatitis B patients, the associations between the study variables and the LSM index were evaluated. Every correlation that was found was not statistically significant. Additionally, the LSM's diagnostic value for hepatic steatosis was evaluated. In the treatment group, the test showed limited diagnostic value, while in the untreated group, it showed satisfactory diagnostic value.

Conclusions: In patients with hepatitis B, the LSM derived from transient elastography does not show a statistically significant correlation with factors such as age, gender, body mass index (BMI), or degree of hepatic steatosis. According to this study, the LSM number is not a reliable indicator for identifying hepatic steatosis in patients with hepatitis B when compared to the CAP score (AUC = 0.69 and 0.74).

Background/aims: Neurotoxicity is commonly seen in liver transplant (LT) patients receiving tacrolimus. We sought to determine the impact of LCP tacrolimus on neurologic toxicity in LT recipients.

Methods: This single-center, semiblinded, parallel group randomized controlled trial compared neurotoxicity burden in LT patients receiving immediate-release (IR) tacrolimus versus LCP tacrolimus. Thirty LT recipients transplanted between January 2020 and February 2022 were enrolled between 15 and 364 days posttransplant and followed for 6 months postrandomization. The primary endpoint was change from baseline to 6 months in composite Patient Global Impression of Improvement (PGI-I) score. Select secondary endpoints included change in Fahn-Tolosa-Marin (FTM) Tremor Rating Scale, IMAB-Q10, SF-12, and Medical Symptom Validity Test (MSVT) scores.

Results: No significant differences were seen in composite PGI scores, though all patients saw improvement in overall PGI scores (IR -5 [-13.5 to -0.25] vs. LCP -4 [-9.5 to -0.5], p = 0.78). Other tests examining neurotoxicities showed no difference between groups but an overall trend toward improvement in symptoms between baseline and end of study. One episode of moderate rejection (rejection activity index [RAI] score of 6) was reported in the LCP group, with no episodes in the IR group (p = 0.31). No graft loss or mortality occurred in either group.

Conclusions: Our study showed LCP tacrolimus had similar rates of neurotoxicity in LT recipients compared to IR without increasing the risk of rejection, graft loss, or mortality; these results suggest LCP tacrolimus can be a safe alternative in LT recipients.

Trial registration: ClinicalTrials.gov identifier: NCT03823768.