Advanced liver fibrosis is associated with decreased gait speed in older patients with chronic liver disease.

This study investigated whether the progression of liver fibrosis affects the prevalence of sarcopenia and incidence of decreased gait speed in older patients with chronic liver disease (CLD). Patients with CLD aged ≥ 60 years were classified into low, intermediate, and high fibrosis 4 (FIB-4) index groups according to the degree of liver fibrosis. The prevalence of sarcopenia and incidence of decreased gait speed (< 1.0 m/s) were compared among the three groups. Logistic regression analysis was performed to investigate factors affecting the risk of decreased gait speed. No significant difference was observed in the prevalence of sarcopenia among the three groups, but the incidence of decreased gait speed significantly differed (p = 0.029). When analyzed individually, a significant difference in decreased gait speed incidence was observed between the high and low FIB-4 index groups (p = 0.014). In logistic regression analysis, the progression of liver fibrosis (odds ratio: 1.32, 95% confidence interval: 1.13-1.55) and lower extremity muscle strength (LEMS) (odds ratio: 0.92, 95% confidence interval: 0.88-0.97) were significantly associated with decreased gait speed. As liver fibrosis progresses in older patients with CLD, it becomes important to focus on not only skeletal muscle mass and grip strength, but also gait speed and LEMS.

Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab.

INTRODUCTION: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. METHODS: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. RESULTS: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. CONCLUSION: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Impact of fibrosis on liver-related event incidence in nonalcoholic fatty liver disease: A multicenter observational study.

AIM: There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. METHODS: Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. RESULTS: The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. CONCLUSIONS: The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.

Impact of skeletal muscle volume on patients with BCLC stage-B hepatocellular carcinoma undergoing sorafenib therapy.

AIM: Skeletal muscle volume has been reported to be an important factor that determines overall survival (OS) and post-progression survival (PPS) in patients with hepatocellular carcinoma (HCC). However, the impact of skeletal muscle volume on HCC with Barcelona Clinic Liver Cancer (BCLC) stage B (BCLC-B) remains unclear. We conducted sub-analyses of a previous study on BCLC-B and compared our findings with data on HCC with BCLC stage C (BCLC-C). METHODS: We retrospectively enrolled 356 patients with HCC (BCLC-B, n = 78; and BCLC-C, n = 278) undergoing sorafenib therapy. Prognostic factors were analyzed using various parameters, including skeletal muscle volume. Muscle volume (MV) depletion was designated as less than the median value of the skeletal muscle index for each gender (cutoff value: 45.0 cm2 /m2 for male and 38.0 cm2 /m2 for female participants). RESULTS: Both OS and PPS showed no significant differences in patients with non-MV depletion and those with MV depletion in the BCLC-B group (Median OS [MST] 19.3 vs. 13.5 months [p = 0.348]; median PPS 9.7 vs. 10.8 months [p = 0.578]). In the BCLC-C group, patients with non-MV depletion had a significantly longer OS and PPS compared to patients with MV depletion (MST 12.4 vs. 9.0 months [p = 0.001] and median PPS 7.9 vs. 5.4 months [p = 0.002]). Multivariate analysis revealed that MV depletion was an independent prognostic factor of OS and PPS in the BCLC-C group but not in the BCLC-B group. CONCLUSIONS: Skeletal muscle volume showed little impact on the clinical outcomes of patients with BCLC-B undergoing sorafenib therapy.

Clinical features of patients with chronic liver disease in Japan related to alcohol use: Nationwide examination using alcohol use disorders identification test.

AIM: Patients often do not respond truthfully to physicians' interviews concerning alcohol. Few reports regarding the level of alcohol dependence in patients with chronic liver disease (CLD) have been presented. This study aimed to elucidate severity distribution in patients with CLD using the alcohol use disorders identification test (AUDIT). METHODS: From March to June 2022, 2034 Japanese outpatients with CLD, including 415 cases associated with hepatitis C virus, 436 with hepatitis B virus, 173 with alcohol-related liver disease (ARLD), and 1010 with other factors, were interviewed using AUDIT. Clinical features related to alcohol use in these patients were then retrospectively evaluated. RESULTS: In all patients, an AUDIT score 8-14 (harmful use) was noted in 5.8% of hepatitis C virus, 8.9% of hepatitis B virus, 24.3% of ARLD, and 4.4% of other groups, respectively (P < 0.001), while a score ≥15 (dependency) was noted in 3.4%, 3.0%, 27.7%, and 1.9%, respectively (P < 0.001). When the country was divided into regions, the percentages remained similar. Comparisons between patients with and without an AUDIT score ≥8 (n = 1412), performed after exclusion of those without related data (n = 622), showed no significant differences for hepatic reserve function, while those with harmful alcohol use were significantly younger (66 vs. 70 years, P = 0.006) and had a larger percentage of men (80.4% vs. 45.1%, P < 0.001). CONCLUSION: Harmful alcohol and alcohol dependency were observed in approximately 10% of patients with viral or non-viral CLD, after excluding patients with ARLD. Assessment of alcohol intake by use of the AUDIT questionnaire as well as adequate intervention should be considered necessary.

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Management of Systemic Therapies and Hepatic Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma Based on Sarcopenia Assessment.

Background: Sarcopenia, defined as the loss of skeletal muscle mass (MM), physical performance, and strength, has been associated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients treated with several therapies. As systemic therapies, including molecular targeted agents, have a strong impact on sarcopenia, we aimed to review the impact of sarcopenia in patients receiving systemic therapies, especially sorafenib and hepatic arterial infusion chemotherapy (HAIC). Summary: Several studies have demonstrated that sarcopenia is associated with poor clinical outcomes in patients receiving sorafenib or lenvatinib, while HAIC has no association with overall survival (OS) and sarcopenia. Furthermore, based on our previous study, we developed the management of sorafenib score (MS score) to stratify patients' survival according to the positivity of three parameters (skeletal MM, disease control of sorafenib, and post-sorafenib therapy), ranging from 0 to 3. Patients with an MS score ≥2 (median survival time [MST], 16.4 months) showed significantly longer survival than those with an MS score ≤1 (MST, 8.4 months) (p < 0.001). This result indicates that patients need at least two positive parameters to prolong OS. Although performance status (PS) has been used in the Barcelona Clinic Liver Cancer staging system, we consider that the assessment of sarcopenia has the potential to replace PS. Key Messages: Sarcopenia is associated with poor clinical outcomes in patients of HCC receiving sorafenib or lenvatinib. The MS score, based on the positivity of three prognostic factors, including skeletal MM, in patients receiving sorafenib, can be a reliable indicator of prolonged survival.

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma.

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin-bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

Proposal for new sleep disorder criteria in patients with chronic liver disease: Influence of liver-related complications.

AIM: Sleep disorder is common in patients with chronic liver disease (CLD). Liver-related silent complications, including muscle cramps, covert hepatic encephalopathy (HE), and sarcopenia, often reduce the quality of life of patients with CLD and have been reported to cause sleep disorders. In this study, we clarified the prevalence of liver-related complications associated with sleep disorders in patients with CLD. METHODS: We conducted a multicenter cohort study of 271 patients with CLD. The Athens Insomnia Scale, muscle cramps questionnaires, and Stroop test were used to assess insomnia, muscle cramps, and covert HE, respectively. In addition, sarcopenia, dynapenia, and myopenia were diagnosed according to the guidelines of the Japan Society of Hepatology. RESULTS: In total, 136 patients (50.2%) had sleep disorders. Serum albumin and hemoglobin levels and prothrombin time activity were significantly lower in patients with sleep disorders than in those without sleep disorders. On univariate and multivariate analyses adjusted with inverse probability weighting, muscle cramps, covert HE, and dynapenia were associated with a sleep disorder. Sleep disorder was categorized as follows: cramp, covert HE, dynapenia, multiple complications, and others. In total, 106 of 136 patients (77.9%) with sleep disorder had at least one liver-related complication, whereas 75 patients had multiple liver-related complications. CONCLUSION: Sleep disorder in patients with CLD was classified into four categories (muscle cramp, covert HE, dynapenia, and others). Questionnaire for sleep disorder might be an easy primary step for surveillance of high-risk patients with silent complications associated CLD.

Construction of an anti-hepatitis B virus preS1 antibody and usefulness of preS1 measurement for chronic hepatitis B patients: Anti-HBV PreS1 antibody.

OBJECTIVES: The preS1 region plays an essential role in hepatitis B virus (HBV) infection. We construct an antibody that binds to preS1 and a measurement system for serum preS1 in chronic HBV-infected patients. METHODS: Hybridoma clones that produce anti-preS1 antibodies were obtained by the iliac lymph node method. Epitope mapping was conducted, and an enzyme-linked immunosorbent assay (ELISA)-based method was developed. Using this ELISA system, serum preS1 levels were measured in 200 chronic HBV-infected patients. RESULTS: Eight types of hybridomas were obtained, of which antibody 3-55 using amino acids 38-47 as the epitope showed high binding affinity to preS1. Serum preS1 levels measured by ELISA using 3-55 antibody were correlated with HBsAg, HBcrAg and HBV DNA levels. Among HBeAg-negative patients without antiviral therapeutic objective (HBV DNA <3.3 log IU/mL or alanine aminotransferase ≤30 U/L), preS1 was significantly higher in subjects who had progressed to the point of requiring antiviral therapy compared to subjects who had maintained their status for the preceding three years (p<0.01). CONCLUSIONS: We constructed an antibody against preS1 and an ELISA system capable of measuring serum preS1 levels. PreS1 may serve as a novel tool to predict the need for antiviral therapy in HBeAg-negative HBV-infected patients.

Underestimation of impaired glucose tolerance and usefulness of a continuous glucose monitoring system in chronic liver disease.

BACKGROUND AND AIM: The prevalence of glucose intolerance in chronic liver disease patients is high, but glucose intolerance may be overlooked in a single blood test. The purpose of this study is to evaluate blood glucose variability in patients with chronic liver disease by a continuous glucose monitoring system (CGMS) and to examine the discrepancy between hemoglobin A1c (HbA1c) levels estimated from average blood glucose levels and HbA1c. METHODS: This study included 335 patients with chronic liver disease associated with glucose intolerance. A fasting blood test and 72-h CGMS were performed. The estimated HbA1c was calculated from the average blood glucose level, and the correlation between hepatic functional reserve and blood glucose-related parameters was analyzed. From the obtained data, we created a new formula to calculate HbA1c without using CGMS. RESULTS: As hepatic functional reserve decreased, average blood glucose and insulin resistance increased while HbA1c decreased (P < 0.0001). The discrepancy between the estimated HbA1c calculated from the mean blood glucose level and the serum HbA1c (ΔHbA1c) increased as the liver reserve decreased. Using multiple regression analysis, a formula based on fasting blood glucose, HbA1c, body mass index, albumin, and liver function was constructed, and its validity was demonstrated in a study using a different control group. CONCLUSIONS: Hemoglobin A1c may be underestimated because of decreased hepatic functional reserve. CGMS was useful in assessing accurate glycemic control of blood glucose and in detecting postprandial hyperglycemia and nocturnal hypoglycemia. Patients with chronic hepatic impairment should be corrected for hepatic functional reserve before glycemic control.

Utility of the SARC-F Questionnaire for Sarcopenia Screening in Patients with Chronic Liver Disease: A Multicenter Cross-Sectional Study in Japan.

Diagnosing sarcopenia is challenging. This multicenter cross-sectional study aimed to evaluate the utility of the SARC-F score system for identifying sarcopenia in patients with chronic liver disease (CLD). We enrolled 717 patients from five participating centers who completed the SARC-F between November 2019 and March 2021. Sarcopenia was diagnosed based on the Japan Society of Hepatology Working Group on Sarcopenia in Liver Disease Consensus. Muscle strength was estimated using a grip dynamometer, and muscle mass was assessed using computed tomography or bioelectrical impedance analysis. The association between SARC-F and sarcopenia was analyzed using a logistic regression model. The optimal SARC-F cutoff value for identifying sarcopenia was determined using receiver operating characteristic (ROC) curve analysis. Of the 676 eligible patients, 15% were diagnosed with sarcopenia. The SARC-F distribution was 0 points in 63% of patients, 1 point in 17%, 2 points in 7%, 3 points in 4%, and ≥4 points in 8%. The SARC-F items of "Strength" (odds ratio (OR), 1.98; 95% confidence interval (CI), 1.03-3.80) and "Falls" (OR, 2.44; 95% CI, 1.48-4.03) were significantly associated with sarcopenia. The SARC-F value of 1 point showed a higher discriminative ability for identifying sarcopenia than the 4 points that are conventionally used (p < 0.001), with an area under the ROC curve of 0.68, sensitivity of 0.65, specificity of 0.68, positive predictive value of 0.27, and negative predictive value of 0.92. SARC-F is useful for identifying patients with CLD who are at risk of sarcopenia.

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study.

BACKGROUND: We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. METHODS: The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. RESULTS: NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5-60.3%: P = 0.008), hypertension (48.5-57.4%: P = 0.047), and hyperlipidemia (39.2-53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37-3.61: P = 0.026) and the median platelet count increased (15.1-17.9 × 104/µL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC. CONCLUSIONS: The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib.

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.

Skeletal Muscle Volume Is an Independent Predictor of Survival after Sorafenib Treatment Failure for Hepatocellular Carcinoma.

Few studies exist on the relationship between post-progression survival (PPS) and skeletal muscle volume in hepatocellular carcinoma (HCC) patients receiving sorafenib. This study aimed to analyze the effects of muscle volume on clinical outcomes. We retrospectively enrolled 356 HCC patients. Various clinical parameters, including skeletal muscle index, were analyzed as predictors of overall survival (OS), progression-free survival (PFS), and PPS. Patients with high muscle volume showed longer survival or PPS than those with low muscle volume (median survival time: 12.8 vs. 9.5 months, p = 0.005; median PPS: 8.2 vs. 6.3 months, p = 0.015); however, no differences in PFS were found. Multivariate analysis indicated that muscle volume was an independent predictor of PPS and OS. Skeletal muscle volume was a PPS predictor in HCC patients receiving sorafenib. Therefore, survival can be prolonged by the upregulation of skeletal muscle volume, especially in HCC patients with skeletal muscle depletion.

Serum PreS1 and HBsAg ratio reflects liver fibrosis and predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

While the preS1 region of the large hepatitis B surface protein plays an essential role in hepatitis B virus (HBV) infection, the effect of preS1 on liver fibrosis and hepatocarcinogenesis in chronic hepatitis B (CHB) patients is not well known. In this study, we measured serum preS1 levels by chemiluminescent immunoassay technology in 690 CHB patients and evaluated the correlation between serum preS1 levels and HBV, liver function markers and liver inflammation, fibrosis assessed by histological findings. Predictive factors for hepatocellular carcinoma (HCC) development in patients who had no previous history of HCC at the time of preS1 level measurement were also analysed. Median hepatitis B surface antigen (HBsAg) and preS1 levels were 3.08 log IU/mL and 98 ng/mL, respectively. PreS1 values were significantly correlated with serum HBsAg (p <0.001), hepatitis B core-related antigen (HBcrAg) (p <0.001) and HBV DNA levels (p <0.01). PreS1 values were also significantly correlated with serum alanine aminotransferase levels (p <0.001) and were significantly higher in patients who had higher grading of liver inflammatory activity (p <0.05). HBsAg level was correlated, but preS1/HBsAg ratio reflected liver fibrosis staging more directly than HBsAg alone. Multivariate analysis identified age ≥53 years (hazard ratio [HR], 18.360 for <53 years; p = 0.021) and preS1/HBsAg ratio ≥0.12 (HR, 6.205 for <0.12; p = 0.040) as significant and independent factors for HCC development in CHB patients. The preS1/HBsAg ratio directly reflects liver fibrosis, and the ratio might be a predictive marker for HCC development in CHB patients.

Therapeutic effects of sleeve gastrectomy for non-alcoholic steatohepatitis estimated by paired liver biopsy in morbidly obese Japanese patients.

ABSTRACT: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.

Reduced handgrip strength predicts poorer survival in chronic liver diseases: A large multicenter study in Japan.

AIM: Sarcopenia has a high prevalence and can be an adverse predictor in patients with chronic liver diseases (CLDs). We sought to assess the prevalence of sarcopenia and its prognostic significance in patients with CLDs at multiple centers in Japan. METHODS: In this retrospective study, we collated the data of 1624 patients with CLDs (976 men). The diagnosis of sarcopenia was determined by the sarcopenia assessment criteria of the Japan Society of Hepatology. Predictors of mortality were identified using univariate and multivariate analyses. RESULTS: Muscle weakness and skeletal muscle loss occurred in 33.5% and 29.3% of all subjects, respectively, while sarcopenia occurred in 13.9% of all patients. Patients with sarcopenia had a poorer prognosis among all patients, patients with hepatocellular carcinoma (HCC), and those without HCC by log-rank test. The multivariate Cox proportional hazards model identified female gender (hazard ratio [HR], 0.59; p = 0.03), alcoholic liver disease (HR, 4.25; p < 0.01), presence of HCC (HR, 6.77; p < 0.01), Child-Pugh classes A (HR, 1.42; p < 0.05), B (HR, 2.70; p < 0.01), and C (HR, 6.30; p < 0.01), and muscle weakness (HR, 2.24; p < 0.01) as significant adverse predictors. The cut-off values of handgrip strength (HGS) for prognosis determined by maximally selected rank statistics were calculated as 27.8 kg for men and 18.8 kg for women. CONCLUSION: Reduced HGS in patients with CLD was an independent adverse predictor of mortality, with cut-off values of 27.8 kg for men and 18.8 kg for women.

Hepatic Arterial Infusion Chemotherapy Combined with Radiation Therapy for Advanced Hepatocellular Carcinoma with Tumor Thrombosis of the Main Trunk or Bilobar of the Portal Vein.

BACKGROUND: Overall survival of patients with advanced hepatocellular carcinoma (HCC) with Vp4 (tumor thrombosis of the main trunk or bilobar of the portal vein) is extremely poor. PURPOSE: The purpose of this study is to clarify the prognosis of hepatic arterial infusion chemotherapy (HAIC) combined with radiation therapy (RT) for advanced HCC with Vp4 and to analyze the factors that contribute to the prognosis. METHODS: In this retrospective cohort study, 51 HCC patients who were treated with HAIC and RT for portal vein tumor thrombosis and met the following criteria were enrolled: (i) with Vp4; (ii) Child-Pugh score of 5-7; (iii) Eastern Cooperative Oncology Group performance status of 0 or 1; (iv) no history of systemic therapy; and (v) from September 2004 to April 2019. RESULTS: Median overall survival and median progression-free survival were 12.1 and 4.2 months, respectively. Multivariate analysis showed >50% of relative tumor volume in the liver (HR, 3.027; p = 0.008) and extrahepatic spread with (HR, 3.773; p = 0.040) as significant and independent factors of OS. The total overall response rate (ORR) was 19.6%; ORR in main tumor was 13.7%; and ORR in Vp4 was 51.0%. None of the patients who received HAIC combined with RT for advanced HCC with Vp4 developed hepatic failure. This combination therapy of HAIC with RT was safe and well tolerated in all cases. CONCLUSION: Combination therapies of HAIC and RT might be good therapy for advanced HCC with Vp4.

Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.