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 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.

Impact of body fat accumulation on metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease in Japanese male young adults.

AIM: Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) are global concerns. The aim of this study was to reveal the relationship between body composition and NAFLD and MAFLD in male young adults. METHODS: We recruited 335 male graduate students from Gifu University who underwent a health checkup in April 2022. The diagnosis of NAFLD and MAFLD was based on health checkup data and ultrasonography. Muscle and fat mass were measured using bioelectrical impedance analysis and demonstrated as skeletal muscle mass index and fat mass index (FMI), respectively. We assessed factors associated with NAFLD and MAFLD using the logistic regression, decision tree, and random forest analyses. RESULTS: The median age of the participants was 22 years, and 9% were overweight or obese (body mass index ≥25 kg/m2 ), 8% had MAFLD, and 16% had NAFLD. In the multivariate logistic regression analysis, FMI was independently associated with NAFLD (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.26-1.75; p < 0.001) and MAFLD (OR, 1.93; 95% CI, 1.51-2.46; p < 0.001). The decision tree and random forest analyses revealed that the strongest classifier for NAFLD and MAFLD was FMI. Additional analyses among nonobese individuals also showed the strong relationship between FMI, NAFLD, and MAFLD. CONCLUSION: Our study revealed that fat accumulation plays a key role in the development of NAFLD and MAFLD in male young adults, even in nonobese individuals. The results could shed new light on the pathophysiology of NAFLD and MAFLD in young adults.

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.

Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) and large-volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA. METHODS: From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8-week observation period. RESULTS: Among all patients at entry (median age, 63 years; 52% men; 60% Child-Pugh B and 40% Child-Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health-related quality of life (HRQOL) and prominent ascites-related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP. CONCLUSIONS: CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis.

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.

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.

Skeletal Muscle Depletion: A Risk Factor for Pneumonia following Gastric Endoscopic Submucosal Dissection in Elderly Patients.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective treatment for gastric neoplasms in elderly patients; however, it involves several adverse events, including pneumonia. This study aimed to investigate whether skeletal muscle depletion (SMD) was associated with the development of pneumonia in elderly patients who underwent gastric ESD. METHODS: This retrospective observational cohort study included 157 patients (≥80 years) who had undergone gastric ESD. The skeletal muscle cross-sectional area was measured by CT, and the value of the third lumbar vertebra skeletal muscle index (L3 SMI) was evaluated. The SMD was defined as an L3 SMI value ≤38.0 cm2/m2 for women and ≤42.0 cm2/m2 for men. Pneumonia was also diagnosed using CT to identify all included patients. RESULTS: Among 157 patients, 66 (42.0%) showed SMD. In the SMD group, the incidence of pneumonia was 21.2%, whereas it was 7.7% in the non-SMD group (p = 0.018). The longest hospitalization duration was 19 days. Antibiotics were administered in 61.9% of the patients. Procedure time was not significantly different between the groups (72 ± 54 min vs. 62 ± 44 min, p = 0.201). On multivariate analysis, SMD was an independent risk factor for the development of pneumonia (odds ratio = 3.16, 95% confidence interval, 1.18-8.50, p = 0.023). CONCLUSIONS: SMD was not a rare entity in patients aged ≥80 years with gastric neoplasms. SMD was a significant risk factor for pneumonia related to gastric ESD in elderly patients.

Proposal of Stroop test cut-off values as screening for neuropsychological impairments in cirrhosis: A Japanese multicenter study.

AIM: Despite its relevant clinical impact and high prevalence, covert hepatic encephalopathy (HE) still remains underdiagnosed. As patients with liver cirrhosis tend to be older in Japan, more suitable tests for the elderly and cut-off values based on this attribute are needed. Recently, a Stroop test has been developed and validated for the screening and diagnosis of covert HE in the United States. The present study aims to establish the cut-off values of the Stroop test to screen covert HE. METHODS: This study was a prospective multicenter cross-sectional endeavor. We undertook a survey of 311 cirrhotic patients, administering the number connection test (NCT)-A and -B and the Stroop-off and -on test. RESULTS: We determined the cut-off values of Stroop test results for cirrhotic patients in a variety of age ranges. The cut-off value of the Stroop test was strongly correlated with age. There was a significant correlation between the results of NCT-B and age, and Stroop-on test results showed a correlation with serum albumin (Alb) levels. Serum Alb ≤3.2 g/dl could have the potential to be an objective biomarker of covert HE. In addition, stepwise logistic regression analysis revealed a relationship between the results of the Stroop-on test and plasma ammonia levels. CONCLUSIONS: We established the cut-off values of Stroop test results and confirmed the efficacy of the Stroop test as a simple tool for assessing cognitive alterations. The Stroop test could be suitable as a necessary minimum for the diagnosis of covert HE.

Zinc deficiency predicts overt hepatic encephalopathy and mortality in liver cirrhosis patients with minimal hepatic encephalopathy.

AIM: Minimal hepatic encephalopathy (MHE) is associated with poor outcomes and the development of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis (LC). Zinc plays a key role in the detoxification of ammonia, a risk factor of hepatic encephalopathy. This study aimed to investigate whether zinc deficiency predicts OHE occurrence and mortality in LC patients with MHE. METHOD: This retrospective study included 100 LC patients with MHE. MHE was diagnosed using a computer-aided neuropsychiatric test. Predictors associated with the development of OHE were analyzed using the Fine-Gray competing risk regression model. Cox proportional hazards regression analysis was carried out to evaluate the risk factors of mortality. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Of the 100 LC patients with MHE, 41% had zinc deficiency (<60 µg/dl). Zinc deficiency was observed more frequently in the patients with reduced liver function reserve. During the median follow-up period of 9.9 months, 16% of the patients with MHE developed OHE. The patients with zinc deficiency had a higher risk of OHE than those without zinc deficiency (p = 0.03). Zinc deficiency was also associated with poor survival (p = 0.004). Multivariate analyses showed that zinc predicts the development of OHE (subdistribution hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.92-0.99; p = 0.008) and mortality (HR, 0.96; 95% CI, 0.93-0.99; p = 0.02), independently of liver function reserves. CONCLUSION: Zinc deficiency is likely to be a predictor of both OHE development and mortality in LC patients with MHE.

Reduced handgrip strength is predictive of poor survival among patients with liver cirrhosis: A sex-stratified analysis.

AIM: Handgrip strength (HGS) is a marker of sarcopenia and has been used to stratify an individual's risk of death. We aimed to assess the prognostic significance of HGS in patients with liver cirrhosis. METHODS: In this retrospective study, we collated data of 563 consecutive patients admitted to our hospital with cirrhosis (375 men). A dynamometer was used to measure HGS. Body composition (including skeletal muscle and adipose tissue volumes) was estimated using computed tomography. Predictors of mortality were identified using sex-stratified multivariate analyses. RESULTS: After adjustments for age, cirrhosis etiology, Child-Pugh score, and other confounding variables, HGS, but not body composition, was independently associated with mortality in male patients (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.99; P < 0.01) and female patients (HR, 0.91; 95% CI, 0.84-0.99; P = 0.02). Men with low HGS (<30 kg) had a higher risk of mortality (HR, 2.09; 95% CI, 1.39-3.17; P < 0.001), as did women with low (<15 kg) HGS (HR, 2.14; 95% CI, 1.16-4.01; P = 0.02). We could stratify the sex-specific risk of mortality in cirrhotic patients using HGS, regardless of coexistent hepatocellular carcinoma and the Child-Pugh class. CONCLUSIONS: Reduced HGS, rather than skeletal muscle and adipose tissue volumes, is associated with an increased risk of mortality in patients of both sexes with liver cirrhosis. Measurement of HGS is a simple, cost-effective, and appropriate bedside assessment for the prediction of survival in patients with cirrhosis.

Effect of loop diuretics on skeletal muscle depletion in patients with liver cirrhosis.

AIM: Sarcopenia, the loss of skeletal muscle mass, impairs prognosis of patients with liver cirrhosis. The aim of this study was to investigate the effect of loop diuretics, which are frequently used to treat hepatic edema/ascites, on skeletal muscle depletion and the prognosis in patients with liver cirrhosis. METHODS: This retrospective study evaluated 226 patients with liver cirrhosis. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured using computed tomography. The relative change in skeletal muscle area per year (ΔSMA) was calculated, and the association between ΔSMA and therapeutic dosage of loop diuretics was examined. RESULTS: The therapeutic dosage of loop diuretics was inversely correlated with ΔSMA by simple (r = -0.27, P < 0.0001) and multiple regression analyses (t = -3.07, P = 0.002). During a median follow-up period of 49 months, 82 patients died. Overall survival rates were lower in patients treated with loop diuretics at >20 mg than in those who received ≤20 mg (median, 66 vs. 97 months; P = 0.002). Multivariate analysis revealed that loop diuretics of >20 mg (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.03-3.24; P = 0.039) and ΔSMA of ≤-3.1% (HR, 3.87; 95% CI, 2.32-6.60; P < 0.0001) were independently associated with mortality. CONCLUSIONS: A higher dose of loop diuretic use was associated with more rapid skeletal muscle depletion and poor survival in patients with liver cirrhosis, independent of the severity of liver disease.

Prognostic significance of minimal hepatic encephalopathy in patients with liver cirrhosis in Japan: A propensity score-matching analysis.

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) represents the mildest form of the hepatic encephalopathy spectrum. This study aimed to clarify the prognostic significance of MHE in cirrhotic patients. METHODS: This retrospective study evaluated 357 consecutive patients with liver cirrhosis. MHE was diagnosed using a neuropsychiatric test. A propensity score-matching analysis was employed to adjust significant differences in the baseline characteristics between patients with and without MHE. RESULTS: Of 269 eligible patients, 56 patients (21%) were diagnosed as having MHE. The Child-Pugh score, model for end-stage liver disease score, and serum ammonia levels were significantly increased, while serum albumin levels were reduced in patients with MHE. By contrast, no significant difference was found between the two groups in matched patients. During the median follow-up period of 13.4 months, 67 patients (24.9%) died. Overall survival rates were significantly lower in patients with MHE (median, 25.4 vs 48.8 months; P < 0.001). Multivariate analysis revealed that male sex (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.03-3.18; P = 0.038), stage III/IV hepatocellular carcinoma (HR, 6.32; 95% CI, 3.30-12.79; P < 0.001), the Child-Pugh score (HR, 1.35; 95% CI, 1.12-1.62; P = 0.002), and MHE (HR, 1.92; 95% CI, 1.09-3.29; P = 0.024) were independently associated with mortality in all patients as well as in matched patients. CONCLUSION: Minimal hepatic encephalopathy is associated with an increased risk of mortality in patients with liver cirrhosis, independent of hepatocellular carcinoma stage or Child-Pugh score.

Homeostatic Model Assessment of Insulin Resistance for Predicting the Recurrence of Hepatocellular Carcinoma after Curative Treatment.

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan⁻Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 µU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.

Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis.

AIM: Minimal hepatic encephalopathy (MHE) and sarcopenia impair the health-related quality of life and prognosis of patients with liver cirrhosis; however, the relationship between MHE and sarcopenia remains unclear. The aim of this study was to investigate their relationship and to identify the predictors of MHE in cirrhotic patients. METHODS: This retrospective study evaluated 120 cirrhotic patients who were tested for MHE and sarcopenia. Minimal hepatic encephalopathy was diagnosed by using the computer-aided neuropsychiatric test. Sarcopenia was diagnosed based on the assessment criteria recommended by the Japan Society of Hepatology. Muscle mass and muscle strength were measured by using bio-impedance analysis and digital grip strength dynamometer. Univariate and multivariate logistic regression analyses were carried out to identify the predictors of MHE. RESULTS: Of the 120 cirrhotic patients, 28 (23%) and 32 (27%) were diagnosed with MHE and sarcopenia, respectively. The prevalence of MHE was higher in patients with sarcopenia than in those without sarcopenia (P = 0.01). By the univariate analysis, MHE was significantly complicated with sarcopenia (P < 0.01). In the multivariate analysis, sarcopenia (odds ratio = 3.31, 95% confidence interval = 1.19-9.42; P = 0.02) and serum branched-chain amino acids levels <327 nmol/mL (odds ratio = 2.98, 95% confidence interval = 1.08-8.34; P = 0.03) were found to be associated with MHE. CONCLUSIONS: Sarcopenia and serum branched-chain amino acids levels were predictors of MHE. The amelioration of sarcopenia and/or amino acids imbalance may improve MHE in patients with liver cirrhosis.

Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis.

AIM: Sarcopenia impairs the outcome of patients with liver cirrhosis independently of liver function reserves. The aim of this study was to investigate whether the rate of skeletal muscle wasting predicts mortality in cirrhotic patients. METHODS: This retrospective study evaluated 149 cirrhotic patients who visited our hospital between March 2004 and September 2012. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured by computed tomography, from which the skeletal muscle index was obtained for diagnosis of sarcopenia. The relative change in skeletal muscle area per year (ΔSMA/y) was calculated in each patient. Cox proportional hazards regression analysis was performed to evaluate risk factors for mortality. RESULTS: Of the 149 cirrhotic patients, 94 (63%) were diagnosed with sarcopenia. The median of ΔSMA/y in all patients was -2.2%. For patients in Child-Pugh class A, B and C, ΔSMA/y was -1.3%, -3.5% and -6.1%, respectively. During a median follow-up period of 39 months (range, 1-110), 45 patients (30%) died. The optimal cut-off value of ΔSMA/y for predicting mortality was -3.1%; the survival rate in patients with ΔSMA/y of -3.1% or less was significantly lower than in patients with ΔSMA/y of more than -3.1% (P < 0.0001). The multivariate Cox proportional hazards model found ΔSMA/y of -3.1% or less to be significantly associated with mortality in cirrhotic patients (hazard ratio = 2.73, 95% confidence interval = 1.43-5.44, P < 0.01). CONCLUSION: ΔSMA/y is useful for predicting mortality in patients with liver cirrhosis. Management of skeletal muscle may contribute toward improving the outcome of cirrhotic patients.

Efficacy and safety of cisplatin versus miriplatin in transcatheter arterial chemoembolization and transarterial infusion chemotherapy for hepatocellular carcinoma: A randomized controlled trial.

AIM: Transcatheter arterial chemoembolization (TACE) and transarterial infusion chemotherapy (TAI) are the main therapeutic strategies for treatment of advanced hepatocellular carcinoma (HCC). We conducted a randomized controlled trial to compare the efficacy and safety of cisplatin and miriplatin in TACE and TAI. METHODS: Patients with HCC of indication for TACE or TAI were randomly assigned to receive either cisplatin or miriplatin (49 patients per group) between April 2010 and May 2013. The primary end-point was the therapeutic effect (TE) 3 months after initial treatment, and the secondary end-point was overall survival. RESULTS: TE could be evaluated in 26 patients of the cisplatin group and 20 patients of the miriplatin group. In the cisplatin group, 11 (42.3%) and 15 (57.7%) patients were classified as showing TE3 + 4 and TE1 + 2, respectively, while in the miriplatin group, each number was nine (45.0%) and 11 (55.0%) (P = 0.8551). Furthermore, no significant difference in overall survival was found between two groups for all patients (P = 0.905) or those treated only with TAI (10 in the cisplatin group and eight in the miriplatin group; P = 0.695). TE3 + 4 group showed better overall survival than TE1 + 2 group (P = 0.0263). Grade 4 or higher adverse event did not occur in either group. Creatinine levels in the cisplatin group rose 3 days after TACE or TAI (P = 0.0397). CONCLUSION: Cisplatin and miriplatin had equal efficacy for TACE and TAI, but cisplatin should be avoided for patients with renal dysfunction or inadequate hydration. Good TE improved overall survival.

Impact of serum glycosylated Wisteria floribunda agglutinin positive Mac-2 binding protein levels on liver functional reserves and mortality in patients with liver cirrhosis.

AIM: Serum glycosylated Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA(+) -M2BP) levels are a non-invasive and reliable marker to assess the degree of liver fibrosis. We investigated the use of WFA(+) -M2BP levels to predict mortality in patients with liver cirrhosis (LC). METHODS: This retrospective study consisted of 59 consecutive patients. Liver fibrosis was estimated by hyaluronic acid (HA), 7S fragment of type IV collagen (7S collagen), aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 index. The severity of liver disease was evaluated by Child-Pugh classification and the Model for End-Stage Liver Disease (MELD) score. Cox proportional hazards regression analysis was performed to evaluate risk factors for mortality, and the diagnostic accuracy of WFA(+) -M2BP levels to predict mortality was examined using receiver-operator curves. RESULTS: Serum WFA(+) -M2BP levels of Child-Pugh class A, B and C had cut-off indexes (COI) of 2.90, 6.15 and 9.45, respectively. WFA(+) -M2BP levels were positively correlated with HA, 7S collagen, APRI, FIB-4 index, Child-Pugh class and MELD score. Multivariate analysis identified WFA(+) -M2BP levels as an independent risk factor of mortality (hazard ratio = 1.19, 95% confidence interval = 1.02-1.41, P = 0.03), and the optimal cutoff point to predict mortality was 5.0 COI. The survival rate was significantly lower in patients with WFA(+) -M2BP levels 5.0 or more COI than in patients with WFA(+) -M2BP of less than 5.0 COI (P = 0.002). CONCLUSION: Serum WFA(+) -M2BP levels were significantly correlated with both liver function reserves and liver fibrosis, and were independently associated with mortality in patients with LC.