Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non‐specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient‐reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health‐care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non‐alcoholic steatohepatitis (NASH)‐specific instrument called “Chronic Liver Disease Questionnaire (CLDQ)‐NAFLD/NASH” has been developed. CLDQ‐NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ‐NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test–retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ‐NAFLD/NASH. We also examine the validity of CLDQ‐NAFLD/NASH in Japanese patients and alterations in CLDQ‐NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ‐NAFLD/NASH in phase 3 clinical trials and in a real‐world clinical setting.

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20–40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI −0.17 vs. −0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240–4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062–4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.

The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). 1383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (<3.5 g/dL). Unadjusted hazard ratio [HR] of the intermediate albumin group, compared with the high albumin group, were 3.6 for death or OLT, 11.2 for liver-related death, 4.6 for HCC, 8.2 for decompensated cirrhosis, and 6.2 for gastroesophageal varices (all risks were statistically significant). After adjusting confounding factors, albumin remained significantly associated with death or OLT (intermediate vs. high albumin group: HR 3.06, 95% confidence interval [CI] 1.59–5.91, p < 0.001; low vs. high albumin group: HR 22.9, 95% CI 8.21–63.9, p < 0.001). Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin.