T he scientific, academic, medical and data science communities have come together in the face of the COVID-19 pandemic crisis to rapidly assess novel paradigms in artificial intelligence (AI) that are rapid and secure, and potentially incentivize data sharing and model training and testing without the usual privacy and data ownership hurdles of conventional collaborations 1,2 . Healthcare providers, researchers and industry have pivoted their focus to address unmet and critical clinical needs created by the crisis, with remarkable results [3][4][5][6][7][8][9] . Clinical trial recruitment has been expedited and facilitated by national regulatory bodies and an international cooperative spirit 10-12 . The data analytics and AI disciplines have always fostered open

Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.

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Background and Aim Although low skeletal muscle mass (LSMM) is known to increase the risk of non‐alcoholic fatty liver disease (NAFLD), limited reports have described the relationship between LSMM and advanced fibrosis. Here, we investigated the association between LSMM and advanced liver fibrosis in NAFLD patients. Methods Fatty liver was diagnosed using ultrasound, and appendicular skeletal muscle mass (ASM) was measured using bioelectrical impedance analysis. LSMM was defined in two ways: ASM/body weight percentage (LSMM‐BW) and ASM/body mass index. Liver fibrosis stage was assessed by two models, the NAFLD fibrosis score and the Fibrosis‐4 index, which determined low and high cutoff values (COVs). Results Of 10 711 NAFLD patients, 615 were diagnosed with LSMM‐BW. LSMM patients were older (47.6 vs 52.5 years, P = 0.001) and had higher body mass index values (23.6 vs 29.1 kg/m2, P < 0.001) and waist circumferences (80.1 vs 93.3 cm, P < 0.001) than non‐LSMM patients. LSMM was an independent risk factor for advanced fibrosis assessed by a low COV for the Fibrosis‐4 index regardless of its classification (adjusted for metabolic and lipid profiles and sex, odds ratio [OR], 1.27–2.01; all P < 0.05). LSMM was an independent risk factor for advanced fibrosis assessed by both COVs of NAFLD fibrosis score (adjusted for obesity, hypertension, lipid profile, and sex; OR, 1.64–2.01, P < 0.01 in the low COV group; OR, 2.68–3.12, P = 0.002 in the high COV group). Conclusions Low skeletal muscle mass is associated with advanced fibrosis in NAFLD patients independent of metabolic risk factors.

Background/Aims: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.<br/>Methods: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.<br/>Results: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, <i>P</i>=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (<i>P</i><0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, <i>P</i>=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20–17.02;<i>P</i>=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04–9.30; <i>P</i>=0.042) in COVID-19 patients.<br/>Conclusions: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

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.

ObjectiveThe 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.DesignRetrospective multicentre cohort study.SettingFive tertiary hospitals of Daegu, South Korea.Participants1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs.MethodsThe 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.OutcomeIn-hospital mortality for any reason within 56 days.ResultsOf 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).ConclusionFIB-4 index is a useful predictive marker for mortality in patients with COVID-19 regardless of its severity.