Hepatology Research最新文献

Background: There are few reports on the factors that contribute to liver function at the time of disease progression after first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). Therefore, our multicenter study investigated these factors in u-HCC patients treated with atezolizumab plus bevacizumab (ATZ/BEV).

Methods: We enrolled 101 patients with u-HCC who had preserved liver function, Child-Pugh (CP) Class A at baseline, and were treated with ATZ/BEV as the first-line systemic chemotherapy. All were evaluated for progressive disease (PD) during the observational period, and those who had Child-Pugh Class A at evaluation of PD were classified as Group A, with those who had Child-Pugh Class B at evaluation of PD being classified as Group B.

Results: Comparing the two groups, Group A had significantly higher platelet counts than Group B (p = 0.008). Receiver operating characteristic curve analysis for differentiating CP Class A versus B at the time of evaluation of PD, using platelet counts, showed that the area under the curve was 0.690 and the optimal cutoff value was 12.8 × 10⁴/μL. Multivariate analysis showed that only the low platelet count was associated with CP Class B at the time of evaluation of PD (< 12.8/≥ 12.8 × 10⁴/μL: OR 3.780, p = 0.022).

Conclusions: The data suggest that the platelet count can be used to predict liver function at the time of evaluation of PD after ATZ/BEV therapy in patients with u-HCC. Treatment strategies in u-HCC patients with low platelet counts should be conducted by taking into account deterioration of liver function after ATZ/BEV therapy.

Background: The Japan Liver Cancer Association and the Japanese Society of Hepato-Biliary-Pancreatic Surgery proposed oncological resectability criteria for hepatocellular carcinoma (HCC), classifying tumors as R, BR1, or BR2. However, serum tumor markers, such as alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), despite their prognostic value, were not incorporated.

Methods: We retrospectively analyzed 803 patients undergoing curative liver resection for HCC. Significant tumor marker elevation (TM-high) was defined as AFP > 500 ng/mL or DCP > 1000 mAU/mL. Overall survival (OS) and relapse-free survival (RFS) were compared according to resectability status and tumor marker levels.

Results: TM-high status was observed in 171 patients with R (32.3%), 75 patients with BR1 (27.5%), and 46 patients with BR2 (70.1%). In the R group, TM-high patients had significantly worse outcomes than non-TM-high patients (median survival time [MST], RFS: 26.9 vs. 55.9 months, and p < 0.001; OS: 120.7 vs. 160.8 months and p = 0.008). No significant difference in the OS was observed between R/TM-high and BR1/non-TM-high patients (120.7 vs. 103.1 months and p = 0.159) or BR1/TM-high and BR2/non-TM-high patients (58.7 vs. 58.5 months and p = 0.657). Multivariate analyses confirmed that a TM-high status was an independent predictor for both the RFS (HR 1.36 and p < 0.003) and OS (HR 1.50 and p < 0.001).

Conclusion: AFP and DCP provide independent prognostic information beyond the oncological resectability criteria. Incorporating tumor markers may refine risk stratification and optimize multidisciplinary treatment strategies for HCC.

Aim: Curative resection is possible for hepatocellular carcinoma (HCC) if the disease is detected early. However, recurrence patterns are variable, and it is difficult to control recurrent lesions in some cases.

Methods: We identified patients with HCC who underwent curative resection as their initial treatment between January 2011 and December 2020 and divided them into three groups according to recurrence pattern. Treatment of recurrent lesions and patient outcomes were compared between groups, and predictors of recurrence beyond the Milan criteria were identified.

Results: Data for 351 patients were analyzed. During a median observation period of 69.0 months, 132 patients (37.6%) had no recurrence, 90 (25.6%) had recurrence within the Milan criteria, and 129 (36.8%) had recurrence beyond the Milan criteria. Patient outcomes were comparable between the group with recurrence within the Milan criteria and the group without recurrence (hazard ratio 1.019 and P = 0.95). However, outcomes were significantly worse in the group with recurrence beyond the Milan criteria than in the group without recurrence (hazard ratio 5.059 and p < 0.01). Male sex, alfa fetoprotein > 500 ng/mL, PIVKA-II > 400 mAU/mL, two or more tumors, portal vein invasion, and liver cirrhosis were identified as risk factors for recurrence beyond the Milan criteria after curative resection for HCC. Overall survival was stratified by number of risk factors.

Conclusions: This study suggests that the recurrence pattern determines the outcome after curative resection of HCC rather than recurrence itself. Further investigations are needed to develop perioperative treatment for patients with risk factors for recurrence beyond the Milan criteria.

Aim: In patients with decompensated liver cirrhosis, water retention often leads to complications such as acute kidney injury and poor prognosis. Soluble CD14 (sCD14), a marker of bacterial translocation, may have clinical relevance in this setting. Therefore, we aimed to investigate the prognostic value of sCD14 in patients with decompensated liver cirrhosis and water retention, and to determine its association with diuretic responsiveness, acute kidney injury development, and short-term mortality.

Methods: We retrospectively analyzed 134 patients with decompensated liver cirrhosis and refractory fluid retention treated with tolvaptan. Associations between serum sCD14 levels and diuretic response, acute kidney injury development, and liver-related mortality were evaluated. sCD14 was compared with other bacterial translocation markers (soluble CD163 and mannose receptor) in a subset excluding patients with advanced hepatocellular carcinoma.

Results: Lower sCD14 levels were associated with improved short- and long-term diuretic responses and a lower acute kidney injury incidence. Patients with sCD14 ≤ 2340 pg/mL had significantly better liver-related survival than those with higher levels (median survival time: 24.5 vs. 4.8 months, respectively; p < 0.01). In the multivariate analysis, sCD14 > 2340 pg/mL independently predicted liver-related mortality (hazard ratio = 2.71, p < 0.01). Compared with sCD163 and mannose receptor, sCD14 demonstrated superior prognostic value. Concomitant rifaximin use was significantly associated with lower sCD14 levels.

Conclusions: sCD14 is a potential biomarker for predicting prognosis, diuretic response, and acute kidney injury development in patients with decompensated liver cirrhosis and water retention. Its predictive capacity surpasses that of other bacterial translocation markers and may be influenced by administering therapeutic interventions, including rifaximin.

Background: A substantial proportion of chronic hepatitis B (CHB) patients with indeterminate phase have significant liver injury, yet only a small proportion of these patients receive liver biopsy. We compared the clinical characteristics of indeterminate CHB patients with and without liver biopsy.

Methods: A total of 2928 untreated CHB patients with indeterminate phases were retrospectively included. The indeterminate phase was identified and classified based on the AASLD 2018 guidance.

Results: The median age of patients was 39.0 years and male accounted for 65.0%. A total of 288 (9.8%) CHB patients with the indeterminate phase underwent liver biopsy. Patients with liver biopsy were older (42.0 vs. 39.0 years, p < 0.001) and had higher HBV DNA (3.4 log₁₀IU/mL vs. 2.7 log₁₀IU/mL, p < 0.001), APRI (0.42 vs. 0.36, p < 0.001), FIB-4 (1.18 vs. 0.99, p < 0.001), and liver stiffness values (9.9 vs. 6.6 kPa, p < 0.001), whereas lower platelets (169.0 × 10⁹/L vs. 192.0 × 10⁹/L, p < 0.001) than those without liver biopsy. Patients with PLT< 150.0 × 10⁹/L (OR 1.587, 95% CI 1.207-2.085, p < 0.001) and high HBV DNA (OR 1.458, 95% CI 1.298-1.637, p < 0.001) were more likely to receive liver biopsy in the indeterminate phase.

Conclusion: Only 9.8% of indeterminate CHB patients underwent liver biopsy in our cohort. These patients exhibited higher values on noninvasive fibrosis tests. Hepatic histologic findings from biopsied patients should be interpreted with caution and should not be generalized to all patients in the indeterminate phase.

Background: Liver fibrosis is central to chronic liver disease prognosis, including metabolic dysfunction-associated steatotic liver disease (MASLD). Mac-2 binding protein glycan isomer (M2BPGi) is a recognized liver fibrosis marker, but lacks an established reference range in healthy populations, thereby limiting clinical use.

Methods: This cross-sectional study analyzed 3623 Japanese adults undergoing routine health checks (2020-2021), excluding those with hepatitis B or C. Participants had physical and laboratory assessments, including serum M2BPGi, metabolic parameters, and liver indices. The fatty liver index (FLI) and Fibrosis-4 (FIB-4) index assessed hepatic steatosis and fibrosis. Multiple regression identified independent determinants of M2BPGi, and a normal reference range was established from participants with all metabolic and liver factors within normal limits.

Results: Participants' mean age was 42.3 years (90.5% male). Median M2BPGi was 0.44 COI (IQR: 0.32-0.60). Higher M2BPGi correlated with increased BMI, waist circumference, glucose, lipid levels, liver enzymes, FLI and FIB-4. Regression analysis identified age, sex, BMI, waist, AST, GGT, HDL-C, fasting glucose, and FIB-4 as independent predictors of M2BPGi; alcohol intake was not significant. Females displayed significantly higher M2BPGi than males. Among 1350 participants with completely normal parameters, the reference M2BPGi was 0.41-0.43 COI in male and 0.46-0.54 COI in female.

Conclusions: M2BPGi levels are independently influenced by metabolic factors and sex, and the study establishes sex-specific normal reference ranges in healthy Japanese adults. M2BPGi above these limits should prompt further metabolic and hepatic evaluation.