Dysphagia risk evaluated by the Eating Assessment Tool-10 is associated with health-related quality of life in patients with chronic liver disease.

OBJECTIVE: This study aimed to reveal the prevalence and characteristics of individuals at risk of dysphagia in patients with chronic liver disease (CLD) and its association with health-related quality of life (HRQOL). METHODS: This cross-sectional study included 335 outpatients with CLD. Dysphagia risk, sarcopenia risk, malnutrition risk, and HRQOL were assessed using the Eating Assessment tool-10 (EAT-10), SARC-F, Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT), and Chronic Liver Disease Questionnaire (CLDQ), respectively. Dysphagia risk and low HRQOL were based on EAT-10 ≥3 and CLDQ overall score <5, respectively. Factors associated with dysphagia risk and low HRQOL were assessed using the logistic regression model. RESULTS: Dysphagia risk and lower HRQOL were observed in 10% and 31% of the patients, respectively. Patients with dysphagia risk were older, had lower liver functional reserve, were at higher risk for sarcopenia and malnutrition, and showed lower CLDQ overall score (median, 4.41 vs. 5.69; P < 0.001) than those without. After adjustment, SARC-F (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.02-1.50; P = 0.029) and RFH-NPT (OR, 1.71; 95% CI, 1.04-2.81; P = 0.034) scores were independently associated with dysphagia risk. EAT-10 (OR, 1.17; 95% CI, 1.04-1.30; P = 0.008) and SARC-F (OR, 1.37; 95% CI, 1.18-1.59; P < 0.001) scores were also independently associated with low HRQOL. CONCLUSIONS: Dysphagia risk was prevalent in approximately 10% of patients with CLD and was associated with a risk of sarcopenia and malnutrition. Furthermore, dysphagia risk was related to HRQOL in patients with CLD.

Nutritional counseling improves mortality and prevents hepatic encephalopathy in patients with alcohol-associated liver disease.

AIM: Nutritional counseling improves malnutrition, which determines the prognosis of patients with chronic liver disease. In this study, we investigated the effects of nutritional counseling on mortality and the risk of overt hepatic encephalopathy (HE) in patients with alcohol-associated liver disease. METHODS: In this retrospective cohort study, we included 211 patients with alcohol-associated liver disease who visited Gifu University Hospital between August 2008 and June 2023. Patients were classified into two groups according to the frequency of nutritional counseling by a registered dietitian. The primary outcomes were all-cause mortality and overt HE. Propensity score matching analysis was performed to adjust for potential confounders. RESULTS: Among the patients (median age 67 years; 88% men; and median Model for End-Stage Liver Disease score, 9), 86 (39%) were in the high-frequency (≥2) nutritional counseling group. The high-frequency group had a significantly higher survival rate (46% vs. 25%) and a lower incidence of overt HE (16% vs. 27%) at 5 years than the low-frequency group. Nutritional counseling was associated with a reduced risk of mortality (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.36-0.63) and overt HE (HR 0.64; 95% CI 0.42-0.99), independent of hepatocellular carcinoma and liver function reserve. After propensity score matching, nutritional counseling was still associated with a reduced risk of mortality (HR 0.34; 95% CI 0.19-0.59) and overt HE (HR 0.31; 95% CI 0.11-0.87). CONCLUSIONS: Nutritional counseling effectively improves mortality and prevents overt HE in patients with alcohol-associated liver disease, thereby proving essential for the management of these patients.

A Case of Unresectable Combined Hepatocellular-cholangiocarcinoma Treated with Combination Therapy Consisting of Durvalumab Plus Tremelimumab.

Combined hepatocellular cholangiocarcinoma is a rare and challenging primary liver malignancy that lacks any established standard treatments for unresectable cases. We herein present the first known case of a 49-year-old woman diagnosed with unresectable combined hepatocellular-cholangiocarcinoma, who underwent novel chemotherapy involving durvalumab plus tremelimumab combination therapy. The treatment was temporarily discontinued owing to immune-related adverse events, such as rash, and the patient was subsequently managed with systemic steroid therapy; however, the disease progressed after two courses of this treatment. Further studies are needed to validate the efficacy and safety of immune checkpoint inhibitors such as durvalumab and tremelimumab for the treatment of unresectable combined hepatocellular cholangiocarcinoma.

Animal naming test stratifies the risk of falls and fall-related fractures in patients with cirrhosis.

This study aimed to determine the relationship between animal naming test (ANT), falls, and fall-related fractures in patients with cirrhosis. Cognitive impairment and frailty were assessed using ANT and Karnofsky performance status (KPS), respectively. Factors stratifying the risk of previous falls and fall-related fractures within 1 year were assessed using a logistic regression model. Factors affecting patient performance in ANT were evaluated using multiple regression analysis. Of the 94 patients, 19% and 5% experienced falls and fall-related fractures, respectively. The performance in ANT was worse in patients who experienced falls (11 vs. 18; p < 0.001) and fall-related fractures (8 vs. 16; p < 0.001) than in those who did not. After adjustment, females, KPS, and ANT (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.65-0.93; p = 0.005) were associated with falls, while ANT was significantly associated with fall-related fractures (OR, 0.56; 95% CI 0.35-0.88; p = 0.012). Age and education affected the performance in ANT, whereas the use of Oriental zodiac did not. The ANT is useful for stratifying the risk of falls and fall-related fractures in patients with cirrhosis. The effects of age and education should be considered when applying ANT in the Japanese population.

Lenvatinib Exacerbates the Decrease in Skeletal Muscle Mass in Patients with Hepatocellular Carcinoma, Whereas Atezolizumab Plus Bevacizumab Does Not.

This study aimed to evaluate chronological changes in skeletal muscle index (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI), AFP, PIVKA-II, and ALBI scores during atezolizumab plus bevacizumab (AB) or lenvatinib (LEN) treatment for hepatocellular carcinoma (HCC) and the effect of these changes on survival. A total of 94 patients with HCC (37 were on AB and 57 on LEN) were enrolled. SMI, SATI, VATI, AFP, PIVKA-II, and ALBI scores were analyzed at the time of the treatment introduction (Intro), 3 months after the introduction (3M), at drug discontinuation (End), and the last observational time (Last). The differences between chronological changes were analyzed using the Wilcoxon paired test. The independent predictors for survival and the changes in SMI during AB or LEN (c-SMI%) were analyzed using the Cox proportional hazards model treating all these factors as time-varying covariates and the analysis of covariance, respectively. SMI in the AB group was maintained over time (42.9-44.0-40.6-44.2 cm2/m2), whereas that in the LEN group significantly decreased during the Intro-3M (p < 0.05) and 3M-End (p < 0.05) period (46.5-45.1-42.8-42.1 cm2/m2). SMI (p < 0.001) was an independent predictor for survival together with AFP (p = 0.004) and ALBI score (p < 0.001). Drug choice (AB or LEN; p = 0.038) and PIVKA-II (p < 0.001) were extracted as independent predictors for c-SMI%. AB treatment was significantly superior to LEN in terms of maintaining skeletal muscle, which is an independent predictor for survival.

A survey questionnaire evaluating physical activity patterns and determinants in patients with chronic liver disease.

BACKGROUND: Physical activity can reduce the risk of morbidity and mortality in patients with chronic liver disease (CLD), whereas physical inactivity adversely affects clinical outcomes. Since data on physical activity in CLD are scarce, we conducted a questionnaire survey to assess the physical activity patterns and determinants in patients with CLD. METHODS: We surveyed 437 patients from outpatient clinics at Gifu University Hospital about their physical activity patterns and determinants in 2022 using a validated questionnaire. The primary objective was to examine the proportion of patients who exercised and the clinical characteristics of patients who achieved high levels of physical activity. The secondary objectives were to explore the types, motivations, barriers, and preferences for physical activity. RESULTS: Among the 397 eligible patients (median age 68 years; 51% men; and median Model for End-Stage Liver Disease score 6), 55.4% reported performing physical activity less than once a week. Physical activity frequency was not associated with sex, body mass index, comorbidities, or hepatic reserve. Among the respondents, 60.4% expressed concern regarding physical strength, and 80.6% expressed concern regarding physical inactivity. The main barriers to physical activity were work, household chores, and health problems. However, many respondents expressed their willingness to increase their physical activity frequency with some promotional policies. Walking was the most common physical activity practiced in the past year and the activity most respondents wanted to try in the future. CONCLUSIONS: Patients with CLD are insufficiently active and need physical activity interventions, especially regarding walking.

A case of A20 haploinsufficiency complicated by autoimmune hepatitis.

AIM: A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease that manifests symptoms similar to those of Behçet's disease. However, little is known about the involvement of the liver in HA20. Here, we report a case of HA20 complicated by autoimmune hepatitis (AIH). CASE PRESENTATION: A 33-year-old woman was previously diagnosed with HA20 and chronic thyroiditis, and was treated with prednisolone (PSL; 7.5 mg/day) and levothyroxine sodium hydrate (125 µg/day). She experienced general malaise and jaundice, and biochemical evaluation revealed elevated liver function with an aspartate aminotransferase level of 817 U/L, an alanine aminotransferase level of 833 U/L, and a total bilirubin of 8.3 mg/dL. Pathological evaluation of the liver biopsy revealed interface hepatitis and the patient was diagnosed with acute exacerbation of AIH. Upon increasing the PSL dose to 60 mg/day, the liver enzyme levels rapidly decreased. During tapering of PSL, azathioprine 50 mg/day was added, and there was no relapse of AIH with combination therapy of PSL 7 mg/day and azathioprine 50 mg/day. CONCLUSION: This is the first report of biopsy-proven AIH in an Asian patient with HA20. This case has significant implications for the pathogenesis and treatment of AIH in patients with HA20.

Lenvatinib or Sorafenib Treatment Causing a Decrease in Skeletal Muscle Mass, an Independent Prognostic Factor in Hepatocellular Carcinoma: A Survival Analysis Using Time-Varying Covariates.

This study aimed to assess the effects of lenvatinib (LEN) or sorafenib (SOR) treatment for hepatocellular carcinoma (HCC) on body composition and changes in body composition on survival. This study enrolled 77 HCC patients. Skeletal muscle index (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI), AFP, PIVKA-II, and ALBI scores were analyzed at the time of LEN/SOR introduction, three months after the introduction, at treatment discontinuation, and the last observational time. The differences between chronological changes in these values were analyzed using a paired t-test. The Cox proportional hazards model was used to analyze prognostic factors using time-varying covariates. The chronological changes in each factor were 45.5-43.6-40.6-39.8 (cm2/m2) for SMI, 41.7-41.6-36.3-33.7 (cm2/m2) for SATI, 41.9-41.1-37.1-34.8 (cm2/m2) for VATI, 2.379-26.42-33.61-36.32 (×103 ng/mL) for AFP, 9.404-13.39-61.34-25.70 (×103 mAU/mL) for PIVKA-II, and -2.56--2.38--1.99--1.90 for the ALBI score. The presence of pre-treatment (p = 0.042), AFP (p = 0.002), PIVKA-II (p < 0.001), ALBI score (p < 0.001), and SMI (p = 0.001) were independent prognostic factors. Skeletal muscle mass decreases significantly during LEN/SOR treatment and is an independent prognostic factor for HCC.

FIB­4 index and NAFLD fibrosis score are useful indicators for screening high­risk groups of non­viral hepatocellular carcinoma.

Non-viral hepatocellular carcinoma (HCC) tends to appear in non-cirrhotic livers, rendering it difficult to screen for a high-risk group. The present study aimed to identify the most suitable indicator for screening high-risk groups of non-viral HCC. A total of 190 patients with non-viral HCC, including 126 with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), were enrolled in the present study. A total of two cut-off values, for low and high levels of fibrosis, were set for each of the indicators, including the Child-Pugh score (CPS; 6 and 7), platelet counts (15.8 and 10x104/µl), albumin-bilirubin (ALBI) score (-2.60 and -2.27), fibrosis 4 index (FIB-4 index; 1.30 and 2.67) and NAFLD fibrosis score (NFS; -1.455 and 0.675). The ratio of the number of patients who fell outside the cut-off value for all patients was defined as the overlooking rate. The overlooking rates of CPS, platelet counts, ALBI score, FIB-4 index and NFS for the low fibrosis cut-off value were 41.0, 48.9, 35.8, 4.2 and 5.8%, respectively. When performing analysis limited to the NAFLD cases, those of the FIB-4 index and NFS were 4.8 and 6.3%, respectively. Those for the high fibrosis cut-off value were 79.5, 73.2, 62.6, 30.0 and 37.4%, respectively. On the whole, the present study demonstrates that the cut-off values of ≥1.30 for the FIB-4 index or ≥-1.455 for the NFS may be used to screen high-risk groups of HCC among patients with non-viral hepatitis.

Changes in ALBI Score and PIVKA-II within Three Months after Commencing Atezolizumab Plus Bevacizumab Treatment Affect Overall Survival in Patients with Unresectable Hepatocellular Carcinoma.

In this study, we aimed to evaluate the efficacy and safety of atezolizumab plus bevacizumab (Atez/Bev) treatment for unresectable hepatocellular carcinoma (HCC) and to analyze the factors affecting overall survival (OS). A total of 69 patients who received Atez/Bev at our institutions for unresectable HCC were enrolled in this study. OS and progression-free survival (PFS) were estimated using the Kaplan−Meier method. Changes in clinical indicators within 3 months were defined as delta (∆) values, and the Cox proportional hazards model was used to identify which ∆ values affected OS. The median OS, PFS, objective response rate, and disease control rate were 12.5 months, 5.4 months, 23.8%, and 71.4%, respectively. During the observational period, 62 patients (92.5%) experienced AEs (hypertension (33.3%) and general fatigue), and 27 patients (47.4%) experienced grade ≥ 3 AEs (hypertension (10.1%) and anemia (7.2%)). There was a significant deterioration in the albumin-bilirubin (ALBI) score (−2.22 to −1.97; p < 0.001), and a reduction in PIVKA-II levels (32,458 to 11,584 mAU/mL; p = 0.040) within 3 months after commencing Atez/Bev. Both the worsening ∆ ALBI score (p = 0.005) and increasing ∆ PIVKA-II (p = 0.049) were significantly associated with the OS of patients.

Usefulness of the Global Leadership Initiative on Malnutrition criteria to predict sarcopenia and mortality in patients with chronic liver disease.

AIM: The Global Leadership Initiative on Malnutrition (GLIM) criteria, a newly developed global consensus around core diagnostic criteria for malnutrition, needs validation studies for use in daily clinical settings. This study aimed to determine whether the GLIM criteria could predict sarcopenia and mortality in patients with chronic liver disease (CLD). METHODS: We retrospectively reviewed 858 patients with CLD who were treated at our hospital between March 2013 and December 2019. Sarcopenia was diagnosed based on the criteria proposed by the Japan Society of Hepatology. Malnutrition was assessed using the GLIM criteria, subjective global assessment (SGA), and Royal Free Hospital-global assessment (RFH-GA) and their predictive ability for sarcopenia and mortality were assessed using the logistic regression analysis and the Cox proportional hazards regression model, respectively. RESULTS: Among the eligible 406 patients, 67% were men, the median age was 74 years, and 26% had sarcopenia. The prevalence of malnutrition according to the GLIM criteria, SGA, and RFH-GA was 21%, 35%, and 26%, respectively. Comparing malnourished with well-nourished patients, the odds ratio for complicating sarcopenia was 2.54 (95% confidence interval [CI], 1.44-4.49) for the GLIM criteria, 2.13 (95% CI, 1.09-4.15) for the SGA, and 2.78 (95% CI, 1.56-4.95) for the RFH-GA. During a median follow-up period of 2.0 years, 176 (43%) patients died. After adjusting for confounding factors, the GLIM criteria could independently predict mortality (hazard ratio, 1.95; 95% CI, 1.37-2.81). CONCLUSIONS: The GLIM criteria are useful in identifying sarcopenia and predicting mortality in patients with CLD.