Hepatology Research最新文献

Aim: This study aimed to comprehensively assess the incidence of immune-related adverse events (irAEs) and the detection systems in place for patients with liver cancer undergoing treatment with immune checkpoint inhibitors (ICIs), using a self-administered anonymous questionnaire. The questionnaire was designed to gather crucial insights into the management of irAEs in these patients.

Methods: A self-administered anonymous questionnaire was sent to 456 liver disease collaborative base hospitals and cancer care coordination base hospitals in Japan.

Results: Responses were received from 112 facilities, indicating a response rate of 25%. The region with the highest response rate was Kanto (22%, 24 sites), followed by Kyushu (19%, 21 sites), Chubu (14%, 15 sites), and Kinki (14%, 15 sites). The number of patients with hepatocellular carcinoma (HCC) who received ICI treatment varied, with a mean ± SD of 20.4 ± 19.4 cases per year per facility. The number of full-time physicians who provided ICI treatment for HCC was 4.2 ± 3.3 (mean ± SD), ranging from 0 to 24 per facility. Of these, the majority included hepatologists and oncologists, whose numbers were 3.3 ± 2.4 (mean ± SD) (range, 0-11) and 0.8 ± 1.0 (0-3), respectively. Gastroenterologists and internal medicine specialists participated in the treatment at some facilities.

Conclusions: The survey results revealed that physicians administered ICI therapy for an average of 20 HCC cases per institution, with more than 17 types of irAEs reported. The most common irAEs were hepatic dysfunction, followed by thyroid dysfunction, skin disorders, interstitial pneumonia, and renal dysfunction.

Partial splenic embolization (PSE) has developed as an alternative to surgical splenectomy, mainly to improve hypersplenism and esophagogastric varices in cirrhotic patients. We proposed the novel concept that splenic infarction volume, rather than the splenic infarction ratio, is essential for patients receiving PSE. A splenic infarction volume between 388 and 540 mL is suitable for a sufficient increase in platelet count and less severe PSE-related complications. When restricted to patients with massive splenomegaly >700 mL, the noninfarcted volume of the spleen plays an important role in increasing platelet counts. Based on the splenic volume concept, PSE or laparoscopic splenectomy should be selected. Partial splenic embolization is effective for cancer patients with hypersplenism. Hypersplenism can occur due to portal vein congestion by thrombosis or tumor thrombosis, and hepatic sinusoidal obstruction syndrome after oxaliplatin-including chemotherapy other than liver cirrhosis. Therefore, PSE has been emphasized as a pretreatment intervention for invasive treatments for cancer patients and is applied synchronously with systemic chemotherapy or chemoembolization for patients with liver malignancies. It was reported that additional PSE on chemoembolization can prolong progression-free survival for patients with hepatocellular carcinoma. Moreover, PSE can improve liver function and fibrosis, promote liver regeneration, and activate host immunity. Partial splenic embolization can result in thrombocytosis (<200 × 10⁹/L), but this platelet count is unlikely to promote cancer progression. Partial splenic embolization can improve hypersplenism caused by various factors related to the patient's comorbidity and cancer treatment. Our splenic volume concept helps identify appropriate treatment procedures. A proper understanding of PSE and its dissemination is strongly required.

Aim: The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD.

Methods: This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed.

Results: Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4.

Conclusions: The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Aim: Fontan-associated liver disease (FALD) is a complication after Fontan surgery, and a common cause of liver tumors and cirrhosis. However, no diagnostic criteria for FALD have been established, leading to an underestimation of its prevalence.

Methods: We conducted a national survey to elucidate the characteristics of FALD by collecting data from high-volume centers managing patients who had undergone the Fontan surgery in Japan. In total, 1168 patients were enrolled in the study. First, we examined typical liver findings on ultrasonography after the Fontan surgery. Next, we proposed diagnostic criteria for FALD and advanced FALD based on blood tests, imaging, liver tumors, and pathological examinations. We investigated the sensitivity of histologically diagnosed FALD and advanced FALD based on criteria for blood or imaging tests.

Results: Hepatomegaly, hepatic venous dilatation, caudate lobe enlargement, splenomegaly, liver atrophy, ascites, hepatocellular carcinoma, and hepatic tumors other than hepatocellular carcinoma were observed in 37.7%, 29.9%, 18.4%, 33.2%, 3.2%, 6.0%, 0.85%, and 10.0% of patients, respectively. Typical ultrasound findings of FALD included hepatomegaly, hepatic vein dilatation, and splenomegaly, reflecting liver congestion. With the progression of fibrosis, caudate lobe enlargement and splenomegaly became more prominent. Based on these findings, we proposed diagnostic criteria for FALD. Using these criteria, FALD was diagnosed in 1014 (86.8%) of the patients, and all patients with a pathological diagnosis of FALD were successfully identified. Eight patients were found to have pathological cirrhosis, and all were diagnosed with advanced FALD using our criteria based on blood tests or imaging.

Conclusion: Our diagnostic criteria facilitate detection of FALD or advanced FALD after the Fontan surgery. The accuracy of these criteria should be further evaluated.

Aim: Atezolizumab/bevacizumab is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria is considered a significant adverse event that may cause bevacizumab interruption. Studies have shown that proteinuria might predict improved prognosis, although data are scarce and the association remains controversial, and the mechanisms and predictive factors remain unclear. We aimed to clarify these.

Methods: In this multicenter retrospective study, we screened patients with HCC treated with atezolizumab/bevacizumab. The prognostic impact of grade ≥2 proteinuria was examined in patients with proper clinical data and preserved serum for growth factor analysis. For biomarker analysis predicting proteinuria, baseline serum vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D levels were analyzed.

Results: This study included 75 patients, and 32 (42.7%) experienced grade ≥2 proteinuria. No significant differences were observed between those with or without proteinuria, except for aspartate transaminase and alanine transaminase levels. Time-dependent Cox proportional hazards analysis revealed that grade ≥2 proteinuria was significantly associated with better prognosis (hazard ratio 0.221; 95% confidence interval 0.082-0.592; p = 0.003). In biomarker analysis, low baseline serum VEGF-C and VEGF-D levels were significantly associated with proteinuria, and multivariate analysis demonstrated that baseline serum VEGF-D level was significantly associated with grade ≥2 proteinuria (hazard ratio 0.101; 95% confidence interval 0.029-0.357; p < 0.001).

Conclusions: Grade ≥2 proteinuria in patients with unresectable HCC treated with atezolizumab/bevacizumab indicates a better prognosis, and baseline serum VEGF-D levels can help predict its occurrence. These findings can help in managing adverse events and prognosis in advanced HCC treated with atezolizumab/bevacizumab.

Aim: Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases.

Methods: Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74 years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C, 59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated.

Results: The median observation period was 7.2 months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p = 0.028) (median PFS: without vs. with = 5.6 vs. 2.7 months, p < 0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p = 0.523 and p = 0.038, respectively).

Conclusion: History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

Aim: The term MetALD has been introduced to describe individuals who have metabolic dysfunction-associated steatotic liver disease (MASLD) with greater alcohol consumption, according to the new nomenclature for steatotic liver disease (SLD). This study aims to evaluate the prevalence and clinical characteristics of MetALD in the general population.

Methods: This study is a retrospective, cross-sectional analysis that utilizes the population-based data from the Korea National Health and Nutrition Examination Survey (KNHANES) undertaken between 2019 and 2021. A total of 16 521 participants aged over 18 years were included in the analysis. The presence of hepatic steatosis was determined based on a hepatic steatosis index of 36 or higher.

Results: The prevalence of MetALD was 2.8% (95% confidence interval, 2.5-3.2). Individuals with MetALD were predominantly men (85.4%) and tended to be younger compared to those with MASLD. They showed a higher prevalence of hypertension and had significantly higher levels of fasting glucose, triglycerides, high-density lipoprotein cholesterol, and creatinine compared to individuals with MASLD. The average daily total energy intake was higher in the MetALD group. In addition, the MetALD group had a lower proportion of unemployment with higher income compared to the MASLD group.

Conclusion: Patients with MetALD showed distinct clinical characteristics from those with MASLD. The characteristics of MetALD were similar to those with alcohol-related liver disease. Further analysis of MetALD across various regions and ethnic groups would be needed.

Aim: In Japan, despite low nationwide hepatitis C (HCV) incidence, new infections among people who inject drugs (PWID) and men who have sex with men (MSM) hinder HCV elimination. We explored HCV transmission dynamics and screened HCV recombination within these populations.

Methods: This cross-sectional study recruited HCV-infected patients from Osaka National Hospital, Osaka, Japan, from January 2010 to September 2023. Data from questionnaires and medical records were analyzed. Serum samples collected before anti-HCV treatment underwent HCV RNA extraction, and sequencing of full core (576 bp) and NS5B (267 bp) regions using the Sanger method. Genotype distribution was determined by phylogenetic analysis, and recombinant screening was conducted.

Results: A total of 115 patients were categorized into non-MSM PWID (31), MSM PWID (15), MSM non-PWID (25), and non-MSM non-PWID (44). Positive amplification rates were 99.1% (114/115) for the full-core region, and 96.5% (111/115) for NS5B. No intergenotypic recombination was detected. The predominant genotype in non-MSM PWID was 2a (58%), whereas genotype 1b was most common in MSM PWID, MSM non-PWID, and non-MSM non-PWID groups (79%, 64%, and 68%, respectively). Nucleotide sequence similarity of 94.75%-100% was found in HCV strains from MSM PWID and MSM non-PWID in both full-core and NS5B regions, whereas strains from non-MSM PWID and non-MSM non-PWID were distinct.

Conclusion: The findings suggest that the transmission route in PWID is determined by MSM status, whereas MSM groups showed the same transmission route regardless of PWID. HCV control measures should be focused not only on PWID, but also on MSM to achieve HCV elimination in Japan.