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)].

OBJECTIVE: Studies have demonstrated a high prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients. The aim was to review the effect of tofogliflozin on hepatic outcomes in T2DM patients.
METHODS: A literature search in PubMed, Science Direct and Cochrane Central Register of Controlled Trials was conducted for randomised clinical trials of tofogliflozin by applying predetermined inclusion and exclusion criteria.
RESULTS: A total number of four randomised clinical trials, including 226 subjects, were included in the review. There was a significant decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in the tofogliflozin group as compared to the control or active comparator groups. Additionally, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) levels were also significantly decreased in the tofogliflozin group. However, no significant difference was observed in levels of adiponectin.
CONCLUSIONS: Overall, an improvement in levels of hepatic parameters was observed in T2DM patients with concurrent liver disorders. However, a large number of clinical trials are needed to prove the efficacy of tofogliflozin on hepatic outcomes in patients with T2DM.

Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors.
We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. We used CMA software for statistical analysis.
Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42-60%, I2 = 91%), viral hepatitis was 13.1% (95% CI 9.7-17.6%, I2 = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I2 = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4-13.6%, I2 = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9-44.8, P value < 0.0001, I2 = 64% Q 11.1).
This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000 IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.

UNASSIGNED: Nucleos(t)ide analogues (NAs) are effective in suppressing the replication of the hepatitis B virus. However, NAs cannot effectively induce hepatitis B surface antigen (HBsAg) seroclearance, which represents the optimal treatment endpoint in chronic hepatitis B (CHB). Hence, most CHB patients are advised for indefinite NA therapy, but recent data has supported the concept of finite NA therapy before HBsAg seroclearance.
UNASSIGNED: This article covered the latest evidence on stopping NAs in CHB, with a focused analysis on international guidelines. Articles were retrieved by a literature search on PubMed with the keywords \'chronic hepatitis B,\' \'antiviral therapy,\' \'nucleos(t)ide analogue,\' \'cessation,\' \'stopping\', and \'finite.\' Studies up till 1 December 2022 were included.
UNASSIGNED: Finite NA therapy in CHB has the potential in enhancing HBsAg seroclearance, however it also carries rare but potentially severe risks. NA cessation before HBsAg seroclearance is only suitable for a highly selected group of patients, whereas the majority of CHB patients should be treated indefinitely or until HBsAg seroclearance. Current guidelines have provided recommendations on stopping NAs, but further research is required to optimize the monitoring and retreatment protocol after stopping NAs.

The use of non-nutritive sweeteners (NNSs) is dramatically increasing in food commodities, and their effects on biochemical parameters have been the subject of great controversy. Liver enzymes as markers of liver injury may be helpful measures of non-alcoholic fatty liver disease (NAFLD), but the outcomes of randomized controlled trials (RCTs) suggest their associations with NNSs are contentious.
The current study was designed to provide a GRADE-assessed systematic review and meta-analysis of RCTs studying the consequences of NNS consumption on ALT, AST, and GGT concentrations (ie, the 3 main liver enzymes in adults).
Scopus, PubMed, and EMBASE were searched for relevant studies up to April 2021, with no time and language limitations.
Two independent researchers extracted information from qualified studies, and a third researcher rechecked it.
Of 3212 studies, 10 studies that enrolled a total of 854 volunteers were included. A random-effects or fixed-effects model was utilized to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity between studies was evaluated using Cochran\'s Q test and quantified using the I2 statistic. The pooled results demonstrated that, compared with control groups, NNS intake led to nonsignificant reductions in ALT (WMD: -.78, 95% CI: -2.14, .57, P = .25) and GGT (WMD: -.21, 95% CI: -1.46, 1.04, P = .74). Also, a small nonsignificant increasing effect on AST level was found (WMD: .02, 95% CI: -1.26, 1.30, P = .97). NNS significantly reduced AST levels in type 2 diabetes patients when subgroup analyses were performed. Also, in trials with ≥24-week intervention or studies that utilized stevioside for intervention, a significant reducing effect on ALT level was observed.
The results of this study showed that NNS intake has no significant effect on liver enzyme levels in adults.
PROSPERO registration no. CRD42021250067.

UNASSIGNED: Although Remdesivir has been evaluated for the treatment of coronavirus disease 2019 (COVID-19), few study has yet shown effective mortality reduction. It might be because, in almost all those studies, remdesivir therapy was started beyond 7th days from the onset of symptoms when the active viral replications have already gone.
UNASSIGNED: This study reviewed the effectiveness of early remdesivir therapy during viral phase of COVID-19 and safety of its administration at home or community care during the outbreak of COVID-19 from July to September 2021 in Myanmar. We retrospectively reviewed clinical records of 204 high risk COVID-19 patients who had received remdesivir therapy within 7 days from the onset of illness and before oxygen desaturation.
UNASSIGNED: All patients received remdesivir therapy according to standard five days course of 200 mg loading dose on day 1, followed by 100 mg daily for up to 4 additional days. Out of 204 patients, 60.75% (124/204) were aged 60 years and above with comorbidity; 21.1% (43/204) aged under 60 years with comorbidity and 18.1% (37/204) were aged more than 60 years old without comorbidity. The patients who received RDSV therapy within 1-4 days and within 5-7 days were 50.5% (103/204) and 49.5% (101/204) respectively. All patients survived to 21 days without ICU admission or mechanical ventilation. Eighty six percent of patients had no hypoxia and only five percent had moderate to severe hypoxia, requiring oxygen. Those who received RDSV therapy within 1 to 4 days from the onset of symptoms had significantly lower rate of hypoxia compared to those who received remdesivir therapy on 5 to 7 days. After RDSV therapy, increased lymphocyte count and decreased CPR were observed in 74.5% (152/204) and 52.9% (108/204) of the patients respectively. There was no report of major adverse events.
UNASSIGNED: Remdesivir, if given within first 4 days from the onset of symptoms, is the most effective strategy for prevention of oxygen desaturation, further progression of COVID-19 and death although it is still beneficial if given later, days 5 to 7. It is a safe drug to be prescribed in hospital at home care. It may be cost-benefit if high-risk group of patients with COVID-19 were selected for early remdesivir therapy in the community.

Despite controversies, no study has systematically summarized findings from earlier studies on the effect of berberine (BBR)-silymarin on liver enzymes. Therefore, the current systematic review and meta-analysis aimed to investigate the effect of berberis aristate and Silybum marianum on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in adults.
Relevant studies, published up to June 2021, were searched through PubMed/Medline, Scopus, ISI Web of Science, EMBASE and Google Scholar. The mean differences and standard deviations were pooled using a random-effects model. The studies\' quality was evaluated using the Cochrane Risk of Bias Tool.
Out of 80 citations, 5 trials that enrolled 549 participants were included. Berberis aristate and Silybum marianum resulted in no statistically significant change in ALT (weighted mean differences (WMD): -0.39 mg/dl; 95% CI: -1.67 to 0.89, P = 0.55), and AST (WMD: -0.44 mg/dl; 95% CI: -2.02 to 1.14, P = 0.58).
We did not find any significant reduction in liver enzymes following BBR-silymarin consumption in adults. Further clinical trials with high quality according to the challenges mentioned seem to be helpful to use BBR-silymarin as a supplement for improving liver function.

OBJECTIVE: Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins.
METHODS: We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups.
RESULTS: We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins.
CONCLUSIONS: In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients.

BACKGROUND Measuring serum alanine aminotransferase (ALT) enzyme is a routine clinical test commonly used to evaluate abnormalities in the body in general, and in the liver function in particular. Higher ALT levels are associated with some metabolic disorders. The upper limit normal (ULN) is considered as a reliable threshold for the definition of high ALT.
OBJECTIVE: To assess the existing evidence on the ULN for ALT in the general population.
METHODS: PubMed (Medline), EMBASE, Scopus, and Web of Science (ISI) were searched using a specified search strategy.
UNASSIGNED: We collected documents published from 1980 to 2018 in the English language, focusing on human samples at the population level and extracted the data after qualitative evaluation. METHODS We conducted this study in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We used specific search terms and their combinations to find documents from relevant databases. We used a snowballing approach to find documents not captured in the main phase of the search. Two authors separately conducted the search, screened the articles, and selected documents that were qualified for data extraction based on the defined inclusion criteria. Finally, data extraction was conducted by two authors using PRISMA checklist. Reported ULNs for ALT and 95% confidence intervals (CIs) were documented in previously developed datasheets. RESULTS Out of 15242 studies, 47 articles were included for data extraction and analysis. Data were sparse and lacked the consistency to precisely estimate ULN for serum ALT. The ULN of ALT was significantly diverse across various geographical locations and sexes. The lowest value of ULN for ALT was 19 IU/L in Chinese children (age range: 7 to < 10 years), and the highest value of ULN for ALT was 55 IU/L in children from Ghana aged < 5 years.
CONCLUSIONS: The main limitation of the current systematic review was the scarcity of the reported measures for ULN of ALT. CONCLUSION Based on the results of the current systematic review, it is suggested that the normal range of ALT be redefined, but this redefinition should be done according to the localized data. In order to redefine the ULN for ALT, regional differences, methods used in ALT measurements, and ULN determination should be considered.

Current evidence on the beneficial effects of garlic on liver enzymes is contradictory. Therefore, the aim of this systematic review and meta-analysis is to evaluate the effect of garlic supplementation on human liver enzymes, such as Alanine Transaminase (ALT/SGPT) and Aspartate Transaminase (AST/SGOT). To collect the required data, PubMed, Scopus, ISI Web of Science, and Google scholar databases were systematically searched from inception to June 2019. A meta-analysis was conducted using the random-effects model to evaluate the effects of garlic supplementation on ALT and AST levels. The Cochran\'s Q-test and inconsistency index were also used to evaluate heterogeneity among the studies. Among a total of 15,514 identified articles, six studies (containing 301 participants) met the inclusion criteria. Results of the meta-analysis showed that garlic supplementation significantly decreased AST level (Hedges\' g = -0.36, 95% confidence interval [CI]: -0.72, -0.004, p = .047); whereas, it had no significant effect on ALT level (Hedges\' g = -0.22, 95% CI: -0.64, 0.20, p = .310). Results showed that garlic supplementation reduced AST levels significantly; however, had no significant effect on ALT levels. Further studies are still needed to confirm the results.