This study aims to validate the application of abdominal four-dimensional flow magnetic resonance imaging (MRI) for cirrhotic patients and quantify its effectiveness in assessing the hemodynamic impacts of cirrhosis to evaluate varices.

All consecutive patients who underwent MRIs between September 2022 and June 2023 were enrolled. Groups were divided into varicose, non-varicose, and healthy groups. ANOVA and post hoc LSD-t tests were used for statistical analysis. The correlation between hemodynamic parameters and liver function grade was evaluated using Kendall's correlation coefficient.

A total of 80 patients were included (53 cirrhotic, 27 healthy). Significant disparities were found in main portal vein flow (MPV-FR), splenic vein flow (SV-FR), and vessel diameters (MPV-VD, SV-VD) among the groups (p < 0.05). MPV-FR was higher in the varicose group (24.81 ± 8.52) compared to non-varicose (19.52 ± 5.07) and healthy groups (17.26 ± 5.48). The most robust assessment of variceal risk was achieved by combining the flow rates (FRs) and VDs of MPV and SV (AUC 0.83, 95% CI 0.72-0.94).

The combined indices of FRs and VDs of MPV and SV effectively predict the occurrence of varicose veins in cirrhotic patients.

Question Non-invasive prediction of variceal risk is essential for the clinical management of advanced chronic cirrhosis, yet existing clinical examinations are inadequate. Findings The effective assessment of variceal risk was achieved by combining the flow rates and vessel diameters of the main portal vein and splenic vein. Clinical relevance Four-dimensional flow MRI can reveal hemodynamic changes in cirrhotic patients and assist in identifying gastroesophageal varices, serving as a marker for varices risk prediction.

The Streptococcus salivarius (S. salivarius) group, which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut. Researchers have reported that patients with minimal HE had an increased abundance of the S. salivarius group, which is a specific change in the gut microbiota that distinguishes them from healthy individuals. The correlation between the aggregation of specific bacterial species and fibrosis progression in chronic liver disease (CLD) is yet to be fully elucidated.

To quantify S. salivarius using digital PCR (dPCR) as a liver fibrosis marker of CLD.

This study retrospectively analysed 52 patients with CLD. To quantify S. salivarius in patients with CLD using dPCR, we evaluated the specificity and sensitivity of S. salivarius bacterial load using dPCR for a type strain. Next, we evaluated the clinical usefulness of dPCR for S. salivarius load quantification for detecting liver fibrosis in patients with CLD. The liver fibrosis stage was categorized into mild and advanced fibrosis based on pathological findings.

The dPCR assay revealed that S. salivarius was highly positive for the tnpA gene. The lower limit of quantification for dPCR using the tnpA gene with a 1 μL template comprising 1.28 × 102 CFU/mL was 4.3 copies. After considering the detection range in dPCR, we adjusted the extracted DNA concentration to 5.0 × 10-4 ng/μL from 200 mg stool samples. The median bacterial loads of S. salivarius in stool sample from patients with mild and advanced fibrosis were 1.9 and 7.4 copies/μL, respectively. The quantification of S. salivarius load was observed more frequently in patients with advanced fibrosis than in those with mild fibrosis (P = 0.032).

Quantifying of S. salivarius load using digital PCR is a useful biomarker for liver fibrosis in patients with CLD.

The significance of imaging-based assessment of muscles and malnutrition in patients with primary hepatocellular carcinoma (HCC) remains unclear. This study aimed to elucidate the prognostic role of the combination of Low Muscle Volume and Value (LMVV) and malnutrition.

A total of 714 Child-Pugh grade A/ B patients with first-diagnosed HCC were enrolled, and analyzed factors associated with overall survival. LMVV was defined using psoas muscle mass index and computed tomography values of multifidus muscle at the level of the third lumbar vertebra. We used hypoalbuminemia, Child-Pugh grade B, Subjective Global Assessment (SGA) grade B/C, and Royal Free Hospital Nutrition Prioritizing Tool (RFH-NPT) score > 2 as malnutrition factors in this study.

At baseline, 29% showed LMVV, and 59% met one or more of the malnutrition criteria. No items meeting the criteria of LMVV and malnutrition was observed in 41%, 1 of them was found in 29%, and both were found in 29%. The number of items meeting criteria was an independent factor for a shorter survival. The frequency of liver-related deaths did not differ by presence of LMVV alone, while it was associated with malnutrition. In contrast, the incidence of other types of deaths was influenced by LMVV and malnutrition.

The combination of LMVV and malnutrition is a prognostic factor in patients with primary HCC.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.

Introduction Sarcopenia is a common secondary muscle-related complication observed in patients with chronic liver disease (CLD), along with muscle cramping. The present study aimed to assess the daily activity levels to explore the relationship between the number of steps taken and muscle cramping in patients with cirrhosis (LC) in Japan. Methods Fifty patients were enrolled (male 25, Child-Pugh A, B=42:8). Daily steps were recorded over six months using a pedometer, and seasonal sub-analyses were performed. Sarcopenia was diagnosed in accordance with the guidelines of the Japan Society of Hepatology. Results The median number of steps per day was 3,881, with no significant seasonal differences. Muscle cramping, reduced handgrip strength and sarcopenia were noted in 66.0%, 34.0% and 23.9% of the patients, respectively. However, no significant relationships were found between muscle cramping, handgrip strength, and the average number of steps per day. Although no significant differences in daily steps were noted in the comparisons of patients with varying degrees of hepatic function or the sarcopenia status, those with muscle cramping had a worse modified ALBI grade (≥2b) than those without (42.4% vs. 5.9%, P=0.009). The median average number of steps per day was not significantly different between the patients with and without muscle cramping (3,673 vs. 4,775, P=0.292). Conclusions The present study revealed that the average number of steps per day in LC patients is low. Although no significant relationship between daily activity and muscle cramping was observed, the establishment of appropriate intervention strategies to maintain daily activity and prevent sarcopenia progression is urgently required.

Jiang et al explored the diagnostic capabilities of EncephalApp, a smartphone-based Stroop Test, in patients with nonalcoholic liver disease. The study included 160 patients with nonalcoholic cirrhosis and utilized the psychometric hepatic encephalopathy score as a benchmark for diagnosing minimal encephalopathy. The identified optimal cutoff times were > 101.93 seconds for the "off" time and > 205.86 seconds for the combined "on + off" time, demonstrating sensitivities of 0.84 and 0.90, and specificities of 0.77 and 0.71, respectively. The findings suggest the necessity of employing different cutoffs for patients with alcoholic vs nonalcoholic liver cirrhosis, reflecting the distinct pathophysiologies underlying each condition. Additionally, alcohol consumption itself may influence Stroop test outcomes. Therefore, it is reasonable to establish separate benchmarks for alcoholic and nonalcoholic cirrhotic patients. Further validation in larger patient cohorts with clinical outcomes is essential. The demand for noninvasive liver disease assessments remains high in clinical practice.

This study aimed to assess the prognostic significance of hand grip strength (HGS) and skeletal muscle mass index (SMI) in patients with alcohol-related cirrhosis.

535 patients with liver cirrhosis (LC) were assessed for HGS and computed tomography (CT)-based SMI. They were categorized into alcohol-related liver disease (ARLD; n = 226), metabolic dysfunction-associated steatohepatitis (MASH; n = 119), and virus-related cirrhosis (VC, n = 190) groups.

Overall prevalence of sarcopenia was 16.4%, 11.8%, and 27.4% in the ARLD, MASH, and VC groups, respectively. Three factors including low SMI, low albumin (Alb) levels, low sodium (Na) levels, and two factors including low HGS and low Alb levels, and three factors including the presence of ascites, low cholinesterase (Ch-E) levels, and low HGS were identified as prognostic factors for mortality in the ARLD, MASH and VC groups, respectively. In the ARLD group, overall survival (OS) was significantly lower in low SMI + low HGS and normal HGS + low SMI (pre-sarcopenia) than in normal SMI and HGS. OS was significantly lower in sarcopenia than in normal SMI + low HGS (dynapenia). In the MASH group, OS was significantly lower in sarcopenia and dynapenia than in normal SMI and HGS. In the VC group, OS was significantly lower in sarcopenia and dynapenia than in normal SMI and HGS; OS was significantly lower in sarcopenia than in pre-sarcopenia.

In the ARLD group, SMI could serve as a more powerful predictor of survival than HGS.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer deaths worldwide. The etiology of HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). The main pathogenesis of MASLD-related HCC is the hepatic lipid accumulation of hepatocytes, which causes chronic inflammation and the subsequent progression of hepatic fibrosis. Chronic hepatic inflammation generates oxidative stress and DNA damage in hepatocytes, which contribute to genomic instability, resulting in the development of HCC. Several metabolic and molecular pathways are also linked to chronic inflammation and HCC in MASLD. In particular, the MAPK and PI3K-Akt-mTOR pathways are upregulated in MASLD, promoting the survival and proliferation of HCC cells. In addition, MASLD has been reported to enhance the development of HCC in patients with chronic viral hepatitis infection. Although there is no approved medication for MASLD besides resmetirom in the USA, there are some preventive strategies for the onset and progression of HCC. Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class of medications, has been reported to exert anti-tumor effects on HCC by regulating metabolic reprogramming. Moreover, CD34-positive cell transplantation improves hepatic fibrosis by promoting intrahepatic angiogenesis and supplying various growth factors. Furthermore, exercise improves MASLD through an increase in energy consumption as well as changes in chemokines and myokines. In this review, we summarize the recent progress made in the pathogenic mechanisms of MASLD-associated HCC. Furthermore, we introduced new therapeutic strategies for preventing the development of HCC based on the pathogenesis of MASLD.

Cachexia is a systemic response syndrome characterized by disabling wasting during disease progression. This study aimed to elucidate factors associated with cachexia in patients with cirrhosis and to examine the impact of cachexia on patient survival.

This multicenter retrospective cohort study included patients with cirrhosis admitted to two distinct institutes in Japan. Cachexia was diagnosed according to the criteria proposed by the Asian Working Group for Cachexia. Factors associated with cachexia and the prognostic impact of cachexia were assessed using logistic regression and Cox proportional hazards regression, respectively.

Of the 723 patients enrolled (median [interquartile range] age, 71 [64-77] years; 456 [63%] were male; and 390 [54%] had viral hepatitis), 200 (28%) met the criteria for cachexia diagnosis, with the prevalence increasing with Child-Pugh class from A (17%) to B (40%) and C (66%). Multivariable logistic regression analysis revealed that age and indices of liver function reserve, including Child-Pugh score, were associated with cachexia, whereas sex, etiology of cirrhosis, and complications with hepatocellular carcinoma (HCC) were not. During a median follow-up period of 3.2 years, 264 (37%) patients died. Multivariable Cox regression analyses showed that cachexia was independently associated with increased mortality (adjusted hazard ratio, 1.59; 95% confidence interval, 1.43-1.77), along with factors related to liver function, HCC, and alcohol-associated liver disease as the etiology.

Cachexia is associated with poor liver function in patients with cirrhosis and is an independent prognostic factor.

Background/Objective: Recently, there has been an increasing need to implement the diagnosis of the presence of covert hepatic encephalopathy (CHE) in patients with cirrhosis. The aim of this study was to identify novel factors associated with CHE in clinical practice. Methods: This retrospective study enrolled a total of 402 patients with cirrhosis at 17 institutions. The Stroop test was performed to diagnose CHE at each center. Results: The patients comprised 233 males and 169 females, with a median age of 69 (IQR, 61-75) years. The median albumin and 25(OH)D3 levels were 3.9 (3.5-4.3) g/dL and 15.4 (11.0-21.0) ng/mL, respectively. This cohort included 181 patients with esophageal varices (EV). Multivariate analysis revealed that low 25(OH)D3 (p < 0.05) and EV (p < 0.05) were independent risk factors for CHE. When limited to only laboratory factors, low albumin (p < 0.01) and low 25(OH)D3 (p < 0.05) were independent factors for CHE. The optimal cut-off values of albumin and 25(OH)D3 for predicting CHE were 3.7 g/dL and 16.5 ng/mL, respectively. The prevalence of CHE was 59.2% for 25(OH)D3 < 16.5 ng/mL and EV, 53.8% for albumin < 3.7 g/dL and 25(OH)D3 < 16.5 ng/mL, and 66.7% for albumin < 3.7 g/dL, EV, and 25(OH)D3 < 16.5 ng/mL. Conclusions: Low 25(OH)D3 and albumin levels, and the EV were positively associated with CHE in patients with cirrhosis. Specifically, the prevalence of CHE increased with a decrease in 25(OH)D3 levels. Patients with such risk factors should be actively and carefully examined for the presence of CHE.

Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan.

A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated.

Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams.

Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.

This study aimed to evaluate whether the subjective global assessment (SGA) could effectively predict energy malnutrition, as assessed by indirect calorimetry, and mortality in hospitalized patients with cirrhosis. Energy malnutrition was defined by a nonprotein respiratory quotient (npRQ) < 0.85 using an indirect calorimetry. The usefulness of the SGA in identifying energy malnutrition and predicting mortality was assessed by the logistic regression and Cox proportional hazards models, respectively. Out of the 230 patients analyzed, 43% were found to have energy malnutrition. The distribution of SGA classifications was 54% for SGA-A, 32% for SGA-B, and 14% for SGA-C. Multivariable analysis indicated that both SGA-B (odds ratio, 3.59; 95% confidence interval [CI], 1.59-8.10) and SGA-C (odds ratio, 19.70; 95% CI, 3.46-112.00), along with free fatty acids (FFA), were independently linked to energy malnutrition. Regarding mortality, 125 patients (54%) died over a median follow-up period of 2.8 years. After adjustment, SGA-B (hazard ratio, 1.81; 95% CI, 1.08-3.03) and SGA-C (hazard ratio, 3.35; 95% CI, 1.28-8.76) were predictors of mortality in cirrhosis patients, while energy malnutrition and FFA were not. The SGA is a valuable tool for identifying energy malnutrition and predicting mortality in patients with cirrhosis.

Rapid turnover proteins (RTPs), including retinol-binding protein (RBP), prealbumin, and transferrin, are useful in evaluating dynamic nutritional status. This study aimed to investigate the relationship between serum RTP levels and mortality in patients with chronic liver disease (CLD).

We evaluated 341 patients with CLD admitted between October 2011 and December 2021. Those with RBP levels below 2.7 mg/dL for males and 1.9 mg/dL for females were included in the low RBP group. Factors associated with mortality and low RBP were evaluated using the Cox proportional hazard regression and logistic regression models.

The median age of the included patients was 67 years, and 48% were male. The median model for end-stage liver disease (MELD) score was 8 points, and the median RBP, prealbumin, and transferrin levels were 1.5 mg/dL, 11 mg/dL, and 227 mg/dL, respectively. During a median observational period, 23% of the patients died. Multivariate analysis showed that the RBP level (hazard ratio, 0.62; 95% confidence interval [CI], 0.46-0.81) was independently associated with mortality, while prealbumin and transferrin were not. Additional analysis revealed that male sex (odds ratio, 8.62; 95% CI, 2.56-29.00) and albumin level (odds ratio, 0.10; 95% CI, 0.04-0.26) were significantly associated with the low RBP levels in patients with CLD.

The serum RBP level is a dynamic biomarker associated with mortality in patients with CLD, independent of liver functional reserve, and it may be a useful indicator for nutritional intervention in these patients.

In cirrhosis, activation of renin-angiotensin-aldosterone system leads to sodium and water retention causing ascites. Dapagliflozin, a sodium glucose linked transporter-2 inhibitor, induces natriuresis in patients with heart failure. A similar natriuretic effect may improve ascites in patients with cirrhosis. In this pilot study, we evaluated the safety and efficacy of dapagliflozin in patients with cirrhosis and recurrent ascites.

Forty patients with recurrent ascites and cirrhosis were randomized to 1:1 in a double blinded fashion to receive either dapagliflozin (10 mg/day) with standard medical therapy (Group A) or placebo with standard medical therapy (Group B). The primary outcome was control of ascites at 6 months. Secondary outcomes were urine output, 24-h urinary sodium, Child Turcotte Pugh (CTP), model for end-stage liver disease (MELD) scores, survival at 6 months, incidence of acute kidney injury (AKI) and infections.

The 2 groups were comparable at baseline. Control of ascites at 6 months was significantly better in group A than that in Group B (p = 0.04). Change in urinary sodium was significantly higher in Group A (p < 0.001]. However, there was no difference in change in urine output, CTP or MELD scores and survival (65% vs 72.2%, p = 0.75) between the groups at 6 months. Incidence of AKI (50% vs 15%, p = 0.04) and infections (55% vs 20%, p = 0.04) were significantly higher in Group A.

Significantly better control of ascites and higher natriuresis are observed with dapagliflozin. However, it does not improve disease severity scores or survival, and is associated with increased AKI and infections (NCT05014594).

Background/Objectives: Sarcopenia is an important clinical feature of patients with chronic liver disease (CLD). However, special devices are required to determine skeletal muscle mass. We evaluated the usefulness of body surface area (BSA) for estimating muscle mass and diagnosing sarcopenia in patients with CLD. Methods: We retrospectively studied 1889 Japanese patients with CLD who underwent bioimpedance analysis (BIA) (training cohort, n = 983; validation cohort, n = 906). The optimal cutoff values for predicting low skeletal muscle mass index (SMI) were determined using ROC analysis. We also assessed 1229 patients whose BSA and grip strength (GS) data were obtained on the same day and evaluated the diagnostic performance of the determined cutoff values of BSA for the diagnosis of sarcopenia. Results: In the training cohort, a strong correlation was observed between the SMI and BSA (r = 0.883, p < 0.0001). The cutoff values of BSA for predicting low SMI were 1.68 m2 for men and 1.48 m2 for women. Regarding the presence of low SMI, 776 (78.9%) and 730 (80.5%) patients were correctly diagnosed in the training and validation cohorts, respectively. The sensitivity and specificity of the combination of BSA and GS for sarcopenia were 82.7% and 97.1%, respectively, and 1175 patients (95.6%) were correctly diagnosed. Conclusions: BSA was highly correlated with SMI, suggesting that BSA could facilitate noninvasive estimation of low skeletal muscle mass in patients with CLD.

To systematically evaluate the efficacy and safety of tenofovir and entecavir in chronic hepatitis B-related cirrhosis.

A comprehensive search was conducted in databases including PubMed, Web of Science, Embase and Cochrane Library from the inception until June 2024. Studies on the use of tenofovir and entecavir for chronic hepatitis B-related cirrhosis were collected.

A total of 14 studies involving 14,208 patients were included. The meta-analysis revealed that tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality compared to entecavir in East Asian popupation, while in non East Asian populations, the two groups are roughly equivalent. After 48 weeks, the hepatitis B virus-deoxyribonucleic acid clearance rate in the tenofovir group were comparable to the entecavir group. Both tenofovir and entecavir showed similar effect in reducing the incidence of hepatic encephalopathy. Compared with the entecavir group, patients in the tenofovir group, including tenofovir disoproxil fumarate and tenofovir alafenamide fumarate showed a significant increase in estimated glomerular filtration rate after 48 weeks of treatment.

Compared to entecavir, tenofovir significantly reduced the cumulative incidence of hepatocellular carcinoma and cumulative mortality in chronic hepatitis B-related cirrhosis in East Asian population. However, both drugs were comparable in terms of hepatitis B virus-deoxyribonucleic acid clearance and hepatic encephalopathy. Tenofovir did not significantly cause renal dysfunction, but instead improved estimated glomerular filtration rate levels compared with entecavir. Randomized controlled trials with larger sample size are still needed for validation.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024588432.

Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions.

This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated.

CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1 µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60 µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211 days, OHE developed in 18 patients (14.3%). The administration of more than 20 mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207).

Cirrhotic patients with serum zinc levels below 60 µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20 mg or more of furosemide.

Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)-related liver cirrhosis (HCV-LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct-acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin-like metalloproteinase with thrombospondin type-1 motif 13 (ADAMTS13) can predict EGV progression with HCV-LC after SVR achievement.

This retrospective study enrolled 47 patients with HCV-LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty-nine patients did not experience EGV progression after the SVR was achieved (non-EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment.

The EGV progression group had significantly higher plasma VWF antigen levels (p = 0.00331) and VWF-to-ADAMTS13 ratios (p = 0.000249) than the non-EGV progression group. Multivariate logistic regression models found that a VWF-to-ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08-109; p = 0.00138). During the observation period, patients with a VWF-to-ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF-to-ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78-22.96; p = 0.0044).

The VWF-to-ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement.

The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied.

We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated.

Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group).

The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

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.

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.

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).

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.

It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an adequate intervention method for harm reduction of alcohol use, such as brief intervention (BI) or BI and nalmefene, should be considered. This study aimed to elucidate the clinical effectiveness of BI for CLD patients affected by harmful alcohol use.

From June 2021 to 2023, 123 Japanese CLD outpatients (hepatitis B virus : hepatitis C virus : alcoholic liver disease : others = 32:18:42:31) with an Alcohol Use Disorders Identification Test (AUDIT) score of ≥8 at the initial interview and a repeat interview with AUDIT 9 months later were enrolled. Clinical features related to patient behavior following the initial AUDIT interview were retrospectively evaluated, and compared between patients without and with BI treatment.

For the non-BI and BI groups, baseline AUDIT score (median 10 [interquartile range (IQR) 9-13] vs. 12 [IQR 10-17], p = 0.016) and relative change in AUDIT score (median 0 [IQR -3 to 2] vs. -3 [IQR -7 to 0], p < 0.01) showed significant differences, whereas there was no significant difference between the groups for AUDIT score at the time of the second interview (p = 0.156). Following BI, significant improvements were observed for items 1, 2, 3, 4, 5, 8, and 10 of AUDIT (each p < 0.05).

Patients with an alcohol use disorder as well as those with alcohol dependency who received BI showed a significant decline in AUDIT score, although the score of the follow-up AUDIT indicated continued alcohol use disorder. In addition to BI, medication with nalmefene should be considered, based on individual factors.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear.

We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix.

The median age was 70 years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p < 0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p = 0.120). Across 35.7 months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p = 0.001). In the multivariate analysis, high-risk varix (p < 0.001), high baseline gamma-glutamyl transpeptidase levels (p < 0.001), and virologic failure (p = 0.004) were significantly involved in varix-related events.

The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis.

This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively.

Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis.

Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.

Rapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear.

A total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤  - 3.1%), and the association between ΔSMA/year and mortality were examined.

Patients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, - 5.7%) than those with hepatitis B (ΔSMA/year, - 2.8%) and hepatitis C cirrhosis (ΔSMA/year, - 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤  - 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤  - 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12-5.28) and ΔSMA/year ≤  - 3.1% (HR, 3.68; 95% CI 2.46-5.52) were also predictive of mortality.

These results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients.

Primary biliary cholangitis (PBC) is an autoimmune-mediated cholestatic liver disease that can progress to biliary cirrhosis and liver-related death. The associations between baseline myostatin levels and clinical outcomes in PBC patients are unknown. We aimed to clarify the influence of myostatin levels on the clinical outcomes of PBC patients.

A total of 119 PBC patients were analyzed in this study. Myostatin levels were measured in stored sera before ursodeoxycholic acid treatment, and their associations with the clinical features and prognosis of PBC patients were analyzed. We analyzed the correlation between serum myostatin and chemokines/cytokines.

Serum myostatin was significantly lower in PBC patients (2343 pg/mL) than in healthy controls (4059 pg/mL, P < 0.001). The prevalence of patients with low myostatin levels increased according to the severity of histological fibrosis. The serum myostatin concentration was negatively correlated with the IL-6 and leucine-rich α2 glycoprotein levels, but the chemokine concentration was not correlated with the myostatin concentration. Low myostatin in PBC patients was associated with shorter survival without liver-related complications (hazard ratio [HR], 3.598; 95% confidence interval [CI], 1.27-10.1; P = 0.015) and shorter transplant-free survival (HR, 3.129; 95% CI, 1.02-9.56; P = 0.045) independent of pretreatment GLOBE score. Patients with both high pretreatment GLOBE scores and low myostatin levels had poor prognoses (log-rank test: P < 0.001).

A low serum myostatin concentration at diagnosis was associated with poor clinical outcomes. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with PBC.

For cirrhotic refractory ascites, diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management. However, their therapeutic effects are limited, and most refractory ascites do not respond to medication treatment, necessitating consideration of drainage or surgical interventions. Consequently, numerous drainage methods for cirrhotic ascites have emerged, including large-volume paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, automated low-flow ascites pump, cell-free and concentrated ascites reinfusion therapy, and peritoneal catheter drainage. This review introduces the advantages and disadvantages of these methods in different aspects, as well as indications and contraindications for this disease.

Acute kidney injury (AKI) is a serious complication of cirrhosis. This study analyzed the prognostic effect of AKI in patients with cirrhosis and its risk factors, particularly in relation to amino acid imbalance.

This retrospective study reviewed 808 inpatients with cirrhosis at two institutes in Gifu, Japan. AKI was diagnosed according to the recommendations of the International Club of Ascites. Amino acid imbalance was assessed by measuring serum branched-chain amino acid (BCAA) levels, tyrosine levels, and the BCAA-to-tyrosine ratio (BTR). Factors associated with mortality and AKI development were assessed using the Cox proportional hazards regression model with AKI as a time-dependent covariate and the Fine-Gray competing risk regression model, respectively.

Of the 567 eligible patients without AKI at baseline, 27% developed AKI and 25% died during a median follow-up period of 4.7 years. Using a time-dependent covariate, AKI development (hazard ratio [HR], 6.25; 95% confidence interval [CI], 3.98-9.80; p < 0.001) was associated with mortality in patients with cirrhosis independent of potential covariates. In addition, alcohol-associated/-related liver disease, metabolic dysfunction-associated steatohepatitis, Child-Pugh score, and BTR (subdistribution HR 0.78; 95% CI 0.63-0.96; p = 0.022) were independently associated with AKI development in patients with cirrhosis. Similar results were obtained in the multivariate model that included BCAA and tyrosine levels instead of BTR.

AKI is common and associated with mortality in Japanese patients with cirrhosis. An amino acid imbalance is strongly associated with the development of AKI in patients with cirrhosis.

Dual energy X-ray absorptiometry (DXA) is the gold standard for diagnosing sarcopenia. However, comparative studies using bioelectrical impedance analysis (BIA) would be required in the Korean population. This study aimed to evaluate the correlation between total-body bone density measuring devices (Hologic and GE Lunar) and a bioelectrical impedance measurement device (InBody 970) as well as the correlation between upper body muscle mass.

A total of 119 participants were involved in this study, aged 20 to 70 years, with specific body mass index ranges and no severe health conditions used both DXA (or DEXA) and BIA technologies to assess body composition. The participants were scanned using a Hologic QDR-4500W DXA scanner and GE-Lunar Prodigy DXA systems, and the InBody 970 type of multi-frequency BIA machine. Statistical analysis was performed to determine the correlation between the devices, with a coefficient of at least 0.8.

The muscle mass measurement comparisons between the InBody 970 and Hologic devices demonstrated remarkably high correlation coefficients (exceeding 0.9) across all limbs. Similarly, the muscle mass comparison between the Inbody 970 and GE Lunar devices also revealed substantial correlation coefficients, ranging from 0.83 upwards, across all limbs.

Limb muscle mass measurements using Hologic and GE Lunar whole-body DXA and Inbody 970 BIA demonstrated particularly high levels of concordance. In addition, a conversion formula that bridges limb muscle mass measurements from two widely used whole-body DXA machines and a BIA machine will facilitate sarcopenia research and patient management.