In recent years, an increase in the incidence of liver diseases has been reported all over the world. This study aims to comprehensively summarize and quantitatively analyze the existing evidence concerning the effectiveness of grape-derived products on liver enzymes through a systematic review and meta-analytic approach. PubMed, Scopus, Cochrane Library, and ISI Web of Science were comprehensively searched until January 2024. Articles that reported the effect of grape-derived products on serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were included. Weighted mean differences (WMDs) were pooled using a random-effects model. Nine studies were included in the meta-analysis. The results revealed that grape-derived products did not significantly change the concentrations of ALT (WMD: -2.70 IU/L, 95% CI: -6.14 to 0.75, p = 0.12), and AST (WMD: -1.42 IU/L, 95% CI: -3.54 to 0.70, p = 0.18). However, a significant reduction was observed in serum ALP levels (WMD: -5.49 IU/L, 95% CI: -9.57 to -1.4, p = 0.008). The present findings suggest that grape-derived products positively influence serum ALP levels among adults. However, a more comprehensive decision necessitates additional studies.

BACKGROUND: The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.
METHODS: Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).
RESULTS: Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.
CONCLUSIONS: Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.

OBJECTIVE: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia.
METHODS: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes.
RESULTS: Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; P < .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; P < .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; P = .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; P = .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; P > .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, P < .05; 0.39, 95% CI: 0.04-0.73, P < .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo.
CONCLUSIONS: OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.

OBJECTIVE: Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST).
METHODS: The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes.
RESULTS: Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction.
CONCLUSIONS: Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.

OBJECTIVE: A simple noninvasive score, the Agile 3+ score, combining liver stiffness measurement, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for the identification of advanced fibrosis in patients with suspected NAFLD. We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease, so currently, the two terms are interchangeable.
RESULTS: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the April 24, 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤ 0.451) and rule-in (≥ 0.679) cutoffs. We included 6 observational studies (total of 6955 participants) with biopsy-proven NAFLD [mean age 53 (SE 4) years, mean body mass index 30.9 (SE 2.3) kg/m 2 , 54.0% men, prevalence of diabetes 59.6%]. The pooled prevalence of advanced fibrosis (≥ F3) was 42.1%. By the rule-out cutoff, the overall sensitivity and specificity were 88% (95% CI: 81-93%; I2 = 89.2%) and 65% (95% CI: 54-75%; I2 = 97.6%), respectively. By the rule-in cutoff, the overall sensitivity and specificity were 68% (95% CI: 57-78%; I2 =91.1%) and 87% (95% CI: 80%-92%; I2 =96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age ( p < 0.01), body mass index ( p < 0.01), and, although not statistically significant, sex ( p = 0.06).
CONCLUSIONS: Our systematic review and meta-analysis suggests that Agile 3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

BACKGROUND: Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying.
OBJECTIVE: To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.
METHODS: The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.
RESULTS: A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80.
CONCLUSIONS: Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Early identification of dengue patients at risk of adverse outcomes is important to prevent hospital overcrowding in low- to middle- income countries during epidemics. We performed a systematic review to identify which biomarkers measured in first 96 h of fever could predict dengue haemorrhagic fever (DHF, World Health Organization 1997 clinical classification) or severe dengue (SD, WHO 2009, clinical classification). PubMed, Scopus, CINAHL, Web of Science, and EMBASE databases were searched for prospective cohort and nested case-control studies published from 1997 to Feb 27, 2022. The protocol for the study was registered in PROSPERO (ID: CRD42021230053). After screening 6747 publications, and analysing 37 eligible studies reporting on 5925 patients, elevated C-reactive protein, aspartate aminotransferase, interleukin-8 and decreased albumin levels were strongly associated with dengue haemorrhagic fever (by meta-analyses of multiple studies, p < 0.05), while elevated vascular cell adhesion protein 1, syndecan-1, aspartate aminotransferase and C-reactive protein levels were strongly associated with severe dengue (by meta-analyses of multiple studies, p < 0.05). Further 44 and 28 biomarkers were associated with the risk of DHF and SD respectively, but only in a single study. The meta-analyses suggest the importance of early acute inflammation with hepatic involvement in determining the subsequent course of illness in dengue.

Νon-alcoholic fatty liver disease (NAFLD) is a common cause of end-stage liver disease in developed countries. Oxidative stress plays a key role during the course of the disease and vitamin E supplementation has shown to be beneficial due to its antioxidative properties. We aim to investigate the effect of vitamin E supplementation on serum aminotransferase levels in patients with NAFLD. Three electronic databases (MEDLINE, CENTRAL, and Embase) were reviewed for randomized trials that tested vitamin E supplementation versus placebo or no intervention in patients with NAFLD, published until April 2023. A total of 794 patients from 12 randomized trials were included in this meta-analysis. Notwithstanding the studies\' heterogeneity and moderate internal validity in certain cases, among studies testing vitamin E supplementation at 400 IU/day and above, the values of alanine aminotransferase (ALT) were reduced compared with placebo or no intervention [ALT Mean Difference (MD) = -6.99 IU/L, 95% CI (-9.63, -4.35), for studies conducted in Asian countries and MD = -9.57 IU/L, 95% CI (-12.20, -6.95) in non-Asian countries]. Regarding aspartate aminotransferase (AST), patients in the experimental group experienced a reduction in serum levels, though smaller in absolute values [AST MD = -4.65 IU/L, 95% CI (-7.44, -1.86) in studies conducted in Asian populations] and of lower precision in non-Asian studies [MD = -5.60 IU/L, 95% CI (-11.48, 0.28)].

COVID-19 is primarily known for its respiratory tract involvement, often leading to severe pneumonia and exacerbation of underlying diseases. However, emerging evidence suggests that COVID-19 can result in multiorgan failure, affecting organs beyond the respiratory system. We present the case of a 62-year-old male with COVID-19 who developed acute liver failure (ALF) and rhabdomyolysis in the absence of respiratory failure. Initially, the patient presented with significantly elevated aspartate transaminase (5398 U/L) and alanine transaminase (2197 U/L) levels. Furthermore, a prolonged prothrombin time international normalized ratio (INR) of 2.33 indicated the diagnosis of ALF without hepatic coma, according to Japanese diagnostic criteria. The patient also exhibited elevated creatine kinase (9498 U/L) and a mild increase in creatinine (1.25 mg/dL) levels, but both values improved with intravenous fluid support and molnupiravir administration. To our knowledge, this is the first reported case presenting with both ALF and rhabdomyolysis associated with COVID-19. In addition, we review the existing literature to summarize previously reported cases of ALF triggered by SARS-CoV-2. This case report underscores the significance of recognizing COVID-19 as a significant contributing factor in the development of multiorgan failure. Furthermore, it suggests that COVID-19 can lead to severe illness, irrespective of the absence of respiratory failure.

Extreme transaminase elevation > 1000 international units per liter (IU/L) is typically caused by hepatocellular injury due to ischemia, drugs, or viral infection. Acute choledocholithiasis can also present with marked transaminase elevation mimicking severe hepatocellular injury, contrary to the presumed cholestatic pattern.
We searched PubMed/Medline, EMBASE, Cochrane Library, and Google Scholar for studies reporting the proportion of marked elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000 IU/L in patients with common bile duct (CBD) stones. A proportion meta-analysis with a corresponding 95% confidence interval (CI) was used to pool the proportion of patients with extreme transaminase elevation. I2 was used to examine heterogeneity. We used CMA software utilizing a random effect model for statistical analysis.
Three studies (n = 1328 patients) were included in our analysis. The reported frequency of ALT or AST > 1000 IU/L in choledocholithiasis patients ranged between 6 and 9.6%, with pooled frequency of 7.8% (95% CI 5.5-10.8%, I2 61%). The frequency of patients with ALT or AST > 500 IU/L was higher, ranging between 28 and 47%, with pooled frequency of 33.1% (95% CI 25.3-42%, I2 88%).
This is the first meta-analysis to study prevalence of severe hepatocellular injury in patients with CBD stones. Results revealed that approximately one-third of patients with choledocholithiasis present with ALT or AST > 500 IU/L. Furthermore, levels > 1000 IU/L are not uncommon. An elaborate work-up for alternative etiologies of severe transaminase elevation is likely unwarranted in cases with clear evidence of choledocholithiasis.