Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.     

Nonalcoholic Fatty Liver Disease after Liver Transplant

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in the world. The rising prevalence of nonalcoholic steatohepatitis (NASH) has led to a 170% increase in NASH cirrhosis as the listing indication for liver transplantation from 2004 to 2013. As of 2018, NASH has overtaken hepatitis C as an indication for liver transplantation in the USA. After liver transplantation, the allograft often develops recurrent NAFLD among patients with known NASH cirrhosis. In addition to recurrent disease, de novo NAFLD has been reported in patients with other indications for liver transplantation. In this review, we will discuss the risk factors associated with recurrent and de novo NAFLD, natural course of the disease, and management strategies after liver transplantation.     

Serum Resistin Levels in Adult Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Background and AimsPrevious studies reported that serum resistin levels were remarkably changed in patients with nonalcoholic fatty liver disease (NAFLD) but the conclusions were inconsistent. The aim of this study was to investigate accurate serum resistin levels in adult patients with NAFLD.MethodsA complete literature research was conducted in the PubMed, Embase, and Cochrane Library databases, and all the available studies up to 7 May 2020 were reviewed. The pooled standardized mean difference (SMD) values were calculated to investigate the serum resistin levels in patients with NAFLD and healthy controls.ResultsA total of 28 studies were included to investigate the serum resistin levels in patients with NAFLD. Patients with NAFLD had higher serum resistin levels than controls (SMD=0.522, 95% confidence interval [CI]: 0.004–1.040, I²=95.9%). Patients with nonalcoholic steatohepatitis (NASH) had lower serum resistin levels than the healthy controls (SMD=−0.44, 95% CI: −0.83–0.55, I²=74.5%). In addition, no significant difference of serum resistin levels was observed between patients with NAFL and healthy controls (SMD=−0.34, 95% CI: −0.91–0.23, I²=79.6%) and between patients with NAFL and NASH (SMD=0.15, 95% CI: −0.06–0.36, I²=0.00%). Furthermore, subgroup and sensitivity analyses suggested that heterogeneity did not affect the results of meta-analysis.ConclusionsThis meta-analysis investigated the serum resistin levels in adult patients with NAFLD comprehensively. Patients with NAFLD had higher serum resistin levels and patients with NASH had lower serum resistin levels than healthy controls. Serum resistin could serve as a potential biomarker to predict the development risk of NAFLD.     

Methylenetetrahydrofolate Reductase C677T Mutation and Nonalcoholic Fatty Liver Disease

A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is known as one of the causes of hyperhomocyteinemia. The oxidation products of homocysteine can initiate lipid peroxidation, which has a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to assess the possible role of the MTHFR C677T mutation in the progression of simple steatosis to an advanced form of NAFLD. Thirty-four patients with NAFLD diagnosed by histologic analysis and 282 healthy controls were included in the study. The discrimination of nonalcoholic steatohepatitis (NASH) from another NAFLD was made by NAFLD activity score (NAS), and a NAS≥5 was considered NASH. Patients with either NASH or nonalcoholic fatty liver (NAFL) and controls were evaluated for frequency of the MTHFR C677T mutation. The frequency of the MTHFR C677T mutation was 53.5% (CT, 44.7%; TT, 8.9%) in controls and 41.5% (CT, 37.7%; TT, 3.8%) in patients (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34–1.12). There was no statistical difference in the frequency of this genotype between patients with NAFL and those with NASH (36% [CT, 28%; TT, 8%] vs 46.4% [CT, 46.4; TT, 0%]; OR, 0.65; 95% CI, 0.22–1.96). According to this study, the MTHFR C677T mutation does not seem to be a risk factor for the progression of NAFL to NASH.     

Risk Factors and Ultrasound Can Predict Chronic Hepatitis Caused by Nonalcoholic Fatty Liver Disease

The diagnosis of nonalcoholic fatty liver disease (NAFLD) is underrecognized. The aim of this study was to develop a scoring system that separates NAFLD diagnosis as a cause of chronic hepatitis from controls by using clinical features and liver ultrasound. A retrospective review of consecutive NAFLD cases and other liver disease controls was undertaken selecting patients from an abnormal liver function test code. To qualify for analysis all patients had to have elevated liver injury tests for more then 6 months, a biopsy-confirmed diagnosis, and an ultrasound as part of the evaluation. There were 84 cases of NAFLD and 75 liver disease controls. The NAFLD group had a larger body mass index (BMI) (34.9 versus 26.1; P ≤ 0.0001), a larger liver span (9.8 versus 8.1 cm; P ≤ 0.0001), and higher triglycerides (252 versus 142.6; P ≤ 0.0001). The ultrasound reports recorded features consistent with fatty infiltration in 65.5% of NAFLD cases, compared to 5.3% of other liver diseases (P ≤ 0.0001). Diabetes mellitus was found in 35% of NAFLD and 6.7% of other cases (P ≤ 0.0001). The BMI was >30 in 79.8% of NAFLD cases and 22.7% of other liver disease cases (P ≤ 0.0001). The liver span was >8 cm in 78.6% of NAFLD cases and in only 16% of controls (P = 0.0001). On multivariate analysis using logistic regression, the odds ratio of having ultrasound report findings suggestive of fatty infiltration was 15.9 (CI, 4.1–60). The odds ratio was 9.4 (CI, 2.3–37.9) for diabetes, 5.0 (CI, 1.7–14.6) for BMI >30, and 2.3 for liver span >8 cm (CI, 1.36–3.90). A scoring system using clinical features and ultrasound was shown to reliably separate NAFLD from other cases of chronic hepatitis.     

Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available in vitro, in vivo and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.