Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.

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.

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.

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.

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.

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.

Skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma treated with sorafenib.

The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the L3 skeletal muscle index (L3 SMI) was obtained. The factors contributing to overall survival, sorafenib dose reduction, and discontinuation of sorafenib were analyzed using the Cox proportional hazards model. L3 SMI (p = 0.020) and log (α-fetoprotein (AFP)) (p = 0.010) were identified as independent prognostic factors in HCC patients treated with sorafenib. The initial dose of sorafenib (p = 0.008) was an independent risk factor for sorafenib dose reduction, and log (AFP) (p = 0.008) was the only significant risk factor for the discontinuation of this drug. L3 SMI was not a risk factor for either dose reduction (p = 0.423) or the discontinuation (p = 0.132) of sorafenib. A multiple linear regression analysis determined the following relationship between skeletal muscle mass (assessed as L3 SMI) and the explanatory factors: L3 SMI = -0.1896 × (Age) - 10.3441 × (Child-Pugh score) - 9.3922 × (log (AFP)) + 1.6139 × (log (AFP)) × (Child-Pugh score) + 112.9166. Skeletal muscle depletion is inversely associated with age, Child-Pugh score, and log (AFP). Moreover, it is an independent prognostic factor for HCC patients treated with sorafenib.

Free fatty acid as a marker of energy malnutrition in liver cirrhosis.

AIM: Protein-energy malnutrition is frequently observed in patients with liver cirrhosis (LC). Non-protein respiratory quotient (npRQ) measured by indirect calorimetry is a good marker to estimate energy malnutrition, and predicts the prognosis of patients with LC. However, measurement of npRQ is limited because of the high cost of indirect calorimetry. Our aim was to find out an alternative marker to npRQ that can be used in the routine clinical setting. METHODS: One hundred and fifty-six patients with LC were enrolled in this study. Indirect calorimetry and blood examinations were conducted after overnight fasting, and anthropometry was performed by an expert dietician. The correlation between npRQ and other parameters were calculated by simple and multiple regression analysis. Receiver-operator curve (ROC) analysis was used to identify the cut-off value that would best predict the threshold npRQ of 0.85. RESULTS: Plasma levels of free fatty acid (FFA) was significantly correlated with npRQ value by simple (r = -0.39, P < 0.0001) and multiple regression analysis (t = -2.96, P = 0.0052). Free fatty acid rose in parallel with the increasing disease severity as defined by Child-Pugh classification (P < 0.05). FFA was also correlated with increasing oxidation rate of fat (r = 0.38, P < 0.0001) and decreasing oxidation rate of carbohydrate (r = -0.39, P < 0.0001). The cut-off value of FFA to predict npRQ = 0.85 was 660 µEq/L by ROC analysis. CONCLUSION: FFA is a useful alternative marker to represent npRQ in patients with LC.

Impact of serum chemerin levels on liver functional reserves and platelet counts in patients with hepatocellular carcinoma.

Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson's correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = -0.3732, p = 0.0126), serum alanine aminotransferase levels (r = -0.3864, p = 0.0105), and total bilirubin levels (r = -0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis.

[Bacillus cereus septicemia and necrotizing fasciitis in a patient with liver cirrhosis: a case report].

A 54-year-old woman with hematemesis was referred to our hospital. She had a history of liver cirrhosis and diabetes mellitus. After inserting a Sengstaken-Blakemore tube, we performed endoscopic variceal ligation for ruptured esophageal varices. On the third day of admission, she developed septicemia and necrotizing fasciitis caused by Bacillus cereus. She was successfully treated with early debridement of both lower extremities and intravenous treatment with vancomycin, ciprofloxacin, and clindamycin. Although B. cereus is an attenuate bacterium, it can occasionally cause fatal infection in immuno-compromised individuals, such as those with liver cirrhosis.

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 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.