Masatsugu Ohara

Background and Aims: Although the widespread use of direct‐acting antivirals (DAAs) has reduced the proportion of hepatitis C virus (HCV) antibody‐positive patients eligible for antiviral treatment, the current proportion requiring referral for DAA therapy in ophthalmology departments, which have both high testing volumes and high HCV antibody‐positive rates, remains unclear. Methods: This nationwide multicenter retrospective cohort study included HCV antibody‐positive patients identified through testing in ophthalmology departments at 20 institutions in Japan between 2019 and 2023. The proportions of patients requiring referral for DAA therapy were assessed by electronic medical record (EMR) review across all 20 institutions and by a combination of EMR review and HCV antibody titer determination across nine institutions where antibody titers could be measured. Results: A total of 2792 HCV antibody‐positive patients were identified across 20 institutions. Based on EMR review, the proportions requiring referral for DAA therapy were 44.4%, 38.7%, 34.2%, 38.9%, and 42.5% in 2019, 2020, 2021, 2022, and 2023, respectively. Among 1255 HCV antibody‐positive patients from 9 institutions where HCV antibody titers could be determined, the corresponding proportions assessed by combined EMR review and antibody titer determination were 28.4%, 23.7%, 20.8%, 22.4%, and 25.9%, respectively. Despite a decline in HCV antibody‐positive rates over time, the proportion requiring referral remained high. Conclusions: Although the number of HCV antibody‐positive patients in ophthalmology departments has decreased, a considerable proportion could still be considered for DAA therapy. Combining HCV antibody titer determination with EMR review improves the efficiency of identifying patients requiring referral.

Aim: Cachexia in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) is associated with poor outcomes. Although C‐reactive protein (CRP) is used for diagnosis, its limited specificity may hinder detection of cachexia without systemic inflammation. Leucine‐rich α2‐glycoprotein 1 (LRG1) may identify cachexia when CRP is low; however, its significance in LC and HCC remains unclear. Methods: We retrospectively enrolled 243 patients with LC and/or HCC. Cachexia was defined according to the Asian Working Group for Cachexia criteria. Serum LRG1 levels were measured, and associations with cachexia, CRP, and survival were analyzed. Receiver operating characteristic curve analysis determined the optimal LRG1 cutoff. Results: Cachexia, observed in 65 patients (26.7%), was independently associated with shorter survival. Serum LRG1 levels were higher in patients with cachexia than in those without (median, 16.70 vs. 11.55 μg/mL; p < 0.001). Although LRG1 correlated with CRP, high LRG1 was observed in some patients with low CRP. In multivariable analysis, LRG1 remained independently associated with cachexia (odds ratio, 1.060; 95% confidence interval, 1.000–1.130; p = 0.045). The optimal LRG1 cutoff was 15.2 μg/mL; cachexia was more frequent in patients with high LRG1 than in those without (48.75% vs. 15.95%, p < 0.001). Among patients with cachexia having low CRP, 37.5% had high LRG1. In the low‐CRP subgroup, LRG1 remained independently associated with cachexia. Conclusions: Serum LRG1 is associated with cachexia in LC and/or HCC and may provide clinically relevant information not captured by CRP. LRG1 assessment may improve recognition and stratification of cachexia, even in patients with low CRP levels.

Aim: In patients with decompensated liver cirrhosis, water retention often leads to complications such as acute kidney injury and poor prognosis. Soluble CD14 (sCD14), a marker of bacterial translocation, may have clinical relevance in this setting. Therefore, we aimed to investigate the prognostic value of sCD14 in patients with decompensated liver cirrhosis and water retention, and to determine its association with diuretic responsiveness, acute kidney injury development, and short‐term mortality. Methods: We retrospectively analyzed 134 patients with decompensated liver cirrhosis and refractory fluid retention treated with tolvaptan. Associations between serum sCD14 levels and diuretic response, acute kidney injury development, and liver‐related mortality were evaluated. sCD14 was compared with other bacterial translocation markers (soluble CD163 and mannose receptor) in a subset excluding patients with advanced hepatocellular carcinoma. Results: Lower sCD14 levels were associated with improved short‐ and long‐term diuretic responses and a lower acute kidney injury incidence. Patients with sCD14 ≤ 2340 pg/mL had significantly better liver‐related survival than those with higher levels (median survival time: 24.5 vs. 4.8 months, respectively; p < 0.01). In the multivariate analysis, sCD14 > 2340 pg/mL independently predicted liver‐related mortality (hazard ratio = 2.71, p < 0.01). Compared with sCD163 and mannose receptor, sCD14 demonstrated superior prognostic value. Concomitant rifaximin use was significantly associated with lower sCD14 levels. Conclusions: sCD14 is a potential biomarker for predicting prognosis, diuretic response, and acute kidney injury development in patients with decompensated liver cirrhosis and water retention. Its predictive capacity surpasses that of other bacterial translocation markers and may be influenced by administering therapeutic interventions, including rifaximin.

Aim: Patients with chronic liver disease often experience significant physical, psychological, and financial burdens. These burdens result from repeated long‐term hospital visits or admissions caused by progression to decompensated cirrhosis or hepatocellular carcinoma. Patients with viral liver disease may fear discrimination or social prejudice. This study aimed to clarify the employment status of patients with liver disease in Japan and provide basic data to promote support for balancing treatment and work responsibilities. Methods: A cross‐sectional questionnaire survey on employment was conducted among patients attending 22 hospitals across Japan. Results: Of the 4022 respondents, 2183 were analyzed, including 1694 (77.6%) participants with liver disease. Patients with liver disease were predominantly male and in their 60 s. Disclosure of health information to the workplace was significantly lower among patients with viral liver disease (80.8%) than among those without liver disease or with nonviral liver disease. The intention to continue working after diagnosis was significantly higher among patients with malignancies than among those without. However, this intention did not significantly differ between liver disease and non‐liver disease groups. The awareness rate of the support system for balancing treatment and work program was 27.1%, with no significant difference observed between the liver disease and malignancy groups. Awareness was significantly higher in large workplaces, where full‐time occupational health physicians are mandated. Conclusion: Workers with viral liver disease may hesitate to disclose their condition owing to fear of discrimination or prejudice. Therefore, raising awareness of support systems that protect all workers with illnesses, while considering stigma and discrimination, is essential.

Aim: Cirrhotic cardiomyopathy (CCM) is a significant complication of liver cirrhosis; however, its prevalence and impact in Asian populations remain unclear. The aim of this study was to assess the prevalence of CCM in Japanese patients with liver cirrhosis and to evaluate its impact on clinical outcomes.Methods: In this retrospective study, 80 patients with liver cirrhosis confirmed using transient elastography (liver stiffness ≥ 12.5 kPa) were included. Study was performed at Hokkaido University Hospital between January 2014 and April 2024. CCM was diagnosed using the 2019 Cirrhotic Cardiomyopathy Consortium criteria. Subsequently, patient characteristics, survival, and the incidences of decompensation and cardiovascular events were analyzed.Results: The prevalence of CCM was 46.3% (37/80), with 78.4% of patients with CCM showing isolated systolic dysfunction based on global longitudinal strain. Patients with CCM were significantly older, had lower serum ammonia and bilirubin levels, and had higher platelet counts. CCM was associated with a significantly higher incidence of decompensation events (hazard ratio 3.97, 95% confidence interval 1.64–9.61, p = 0.003) and was an independent risk factor for decompensation in the multivariate analysis (hazard ratio 3.24, 95% confidence interval 1.29–8.11, p = 0.012). Patients with and without CCM showed no significant differences in overall survival or cardiovascular events.Conclusions: CCM is prevalent among Japanese patients with liver cirrhosis and is associated with an increased risk of hepatic decompensation. These findings highlight the importance of cardiac evaluation in patients with cirrhosis and suggest that CCM should be considered in the management of liver cirrhosis to improve patient outcomes.

Aim: Cachexia is a systemic response syndrome characterized by disabling wasting during disease progression. This study aimed to elucidate factors associated with cachexia in patients with cirrhosis and to examine the impact of cachexia on patient survival.Methods: This multicenter retrospective cohort study included patients with cirrhosis admitted to two distinct institutes in Japan. Cachexia was diagnosed according to the criteria proposed by the Asian Working Group for Cachexia. Factors associated with cachexia and the prognostic impact of cachexia were assessed using logistic regression and Cox proportional hazards regression, respectively.Results: Of the 723 patients enrolled (median [interquartile range] age, 71 [64–77] years; 456 [63%] were male; and 390 [54%] had viral hepatitis), 200 (28%) met the criteria for cachexia diagnosis, with the prevalence increasing with Child–Pugh class from A (17%) to B (40%) and C (66%). Multivariable logistic regression analysis revealed that age and indices of liver function reserve, including Child–Pugh score, were associated with cachexia, whereas sex, etiology of cirrhosis, and complications with hepatocellular carcinoma (HCC) were not. During a median follow‐up period of 3.2 years, 264 (37%) patients died. Multivariable Cox regression analyses showed that cachexia was independently associated with increased mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.24–2.12), along with factors related to liver function, HCC, and alcohol‐associated liver disease as the etiology. [Correction added on 22 May 2025, after first online publication: The adjusted hazard ratio and confidence interval in the Results section of Abstract have been changed from ‘1.59; 95% and 1.43–1.77’ to ‘1.62; 95% and 1.24–2.12’.]Conclusions: Cachexia is associated with poor liver function in patients with cirrhosis and is an independent prognostic factor.