Background and Aims: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. Methods: Liver cirrhosis patients with Child–Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. Results: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221–0.684, p < 0.001). Conclusion: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

Background: Advanced liver fibrosis is the most important prognostic factor in nonalcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA), growth arrest-specific transcript 5 (GAS5), is associated with the inhibition of liver fibrogenesis, and its levels are decreased in cirrhotic liver. Methods: We analyzed 51 patients with NAFLD, the diagnosis of which was confirmed by liver biopsy. Expression of GAS5 in both the liver and plasma of the patients was analyzed using a quantitative real-time polymerase chain reaction according to the fibrosis stage. Results: Plasma GAS5 expression was significantly higher in patients with advanced fibrosis than in those without. As the fibrosis progressed, GAS5 expression in plasma increased, with the exception of that in cirrhotic livers. Plasma levels of GAS5 were lower in patients with cirrhosis than in those with advanced fibrosis. Conclusion: Elevated circulating levels of the lncRNA GAS5 are associated with the progression of liver fibrosis prior to the development of cirrhosis.

Se Young Jang, M.D., Won Young Tak, M.D., Soo Young Park, M.D., Young-Oh Kweon, M.D., Yu Rim Lee, M.D., Gyeonghwa Kim, Ph.D., Keun Hur, Ph.D., Man-Hoon Han, M.D., and Won Kee Lee, Ph.D.. Ann Lab Med 2021;41:302-9. https://doi.org/10.3343/alm.2021.41.3.302

Objective The reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with severe infection of COVID-19. Design Retrospective multicentre cohort study. Setting Five tertiary hospitals of Daegu, South Korea. Participants 1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs. Methods The clinical and laboratory features of patients with COVID-19 receiving respiratory support were analysed to ascertain the risk factors for mortality using the Cox proportional hazards regression model. The relationship between overall survival and risk factors was analysed using the Kaplan-Meier method. Outcome In-hospital mortality for any reason within 56 days. Results Of the 1005 patients, 289 (28.8%) received respiratory support, and of these, 70 patients (24.2%) died. In multivariate analysis, high fibrosis-4 index (FIB-4; HR 2.784), low lymphocyte count (HR 0.480), diabetes (HR 1.917) and systemic inflammatory response syndrome (HR 1.714) were found to be independent risk factors for mortality in patients with COVID-19 receiving respiratory support (all p<0.05). Regardless of respiratory support, survival in the high FIB-4 group was significantly lower than in the low FIB-4 group (28.8 days vs 44.0 days, respectively, p<0.001). A number of risk factors were also significantly related to survival in patients with COVID-19 regardless of respiratory support (0–4 risk factors, 50.2 days; 49.7 days; 44.4 days; 32.0 days; 25.0 days, respectively, p<0.001). Conclusion FIB-4 index is a useful predictive marker for mortality in patients with COVID-19 regardless of its severity.

Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0–14.9); 4.6 (4.0–6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590–0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25–395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH.