The Baveno meetings, that are held to establish consensus on portal hypertension and its complications, are international conferences held under the auspices of the European Association for the Study of the Liver. The Japanese Society of Hepatology has participated since Baveno VII. As it is often difficult to clearly distinguish cirrhosis from stage F3 advanced fibrosis, the term c (ACLD) is used in Europe and the United States to describe the state progressed from chronic liver disease (CLD). This ACLD is clinically classified into compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH). Furthermore, although the measurement of hepatic venous pressure gradient (HVPG) remains the gold standard for diagnosing portal hypertension, few institutions in Japan currently measure HVPG. In recent years, the use of non-invasive biomarkers for the diagnosis of portal hypertension has become increasingly common.

Liver transplantation, being the only curative treatment for liver failure, is limited by a severe shortage of donor organs, rendering the development of alternative therapeutic strategies urgently needed. Advances in liver organoid technologies derived from pluripotent and tissue stem cells have recently contributed to regenerative medicine approaches aimed at replacing or supplementing lost organ function closer to clinical reality. This review summarizes recent advancements in liver organoid research, including diversification of cellular sources; systematic optimization of culture conditions; and technological developments, such as multicellular organization incorporating nonparenchymal cells and vascularization strategies. Furthermore, to expand our understanding of human-specific disease biology, we introduce patient-derived organoid studies that utilize genome editing, advanced imaging technologies, and multi-omics analyses. Moreover, we briefly discuss emerging bioartificial liver technologies as an example of organoid platform-based regenerative therapeutic strategies. Integrated therapeutic approaches focused on organoid technologies may present a novel paradigm for liver disease research and management.

This study aimed to clarify changes in the hepatitis C virus (HCV) genotype ratios across age groups among HCV-infected individuals in correctional facilities. A majority of the individuals infected with HCV in Japanese correctional facilities have a history of sharing needles to inject stimulants. The participants were 615 prisoners who underwent antiviral treatment for hepatitis C at Miyagi Prison between March 2008 and May 2025. Of these, 8, 181, 249, 167, 1, and 1 had genotypes 1a (1.3%), 1b (29.8%), 2a (41.0%), 2b (27.5%), 3a (0.2%), and 3b (0.2%), respectively. When analyzing year of birth in five-year increments, the proportion of genotypes gradually changed, with 1b, 2a, and 2b being the most common among those born before 1950, between 1951 and 1975, and after 1976.

Background/Aims: We assessed the performance of the fibrosis-3 (FIB-3), fibrosis-4 (FIB-4), and a novel platelet-free cirrhosis outcome risk estimator (CORE) score for the detection of significant liver fibrosis in Japanese individuals undergoing health checkups. Methods: In a cohort of 591 participants, liver stiffness was measured using 2D shear-wave elastography, and a value of ≥7.0 kPa was defined as significant fibrosis. The Areas under the receiver operating characteristic curves (AUROCs) were calculated and stratified according to age, fatty liver, and alcohol consumption history. Results: Significant fibrosis was observed in 53 cases (9.0%). The AUROCs of CORE, FIB-4, and FIB-3 were 0.690, 0.637, and 0.618, respectively. Although not statistically significant, CORE demonstrated a numerically higher overall performance. In the nondrinking subgroup, CORE significantly outperformed FIB-3 (p = 0.045). In multivariate analysis, CORE remained an independent predictor of significant liver stiffness (odds ratio, 1.22; p = 0.005). Conclusions: Although the standalone accuracy of CORE is modest in low-prevalence settings, the platelet-free CORE score represents a highly practical and effective tool for broad screening in primary care and health checkups.

Promoting direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) -positive individuals is an urgent priority. In April 2023, following the strengthening of measures to prevent failures in communicating test results, our hospital established a system for the rapid and efficient identification of treatment candidates. This initiative was implemented through collaboration among the Medical Safety Management Office, Data Center, and Central Laboratory, using data warehouse/business intelligence (DWH/BI) tools while taking HCV antibody titers into consideration. Furthermore, hepatologists played a central role in directly encouraging treatment among HCV-positive patients in collaboration with nonspecialists and affiliated community physicians. Specifically, in the retrospective group, 15 cases (45.5% of HCV-RNA positive cases) received treatment, whereas 33 cases (67.3%) in the prospective group received treatment following identification using DWH/BI tools. Consequently, the annual number of treated cases increased from 6 in 2022 to 18 in 2023 and 24 in 2024. Rapid and efficient identification combined with direct intervention is highly effective in promoting DAA therapy within medical institutions.

A woman in her 60s with hepatocellular carcinoma following sustained virologic response for hepatitis C-related cirrhosis had undergone eight lines of systemic therapy, including atezolizumab plus bevacizumab. After receiving steroid pulse therapy for immune-related pancreatitis, atezolizumab plus bevacizumab was reintroduced. Subsequently, she developed nausea and anorexia. Upper gastrointestinal endoscopy revealed a solitary gastric ulcer and multiple duodenal ulcers. Although acid-suppressive therapy improved the gastric ulcer, the duodenal ulcers persisted. Biopsy was performed to differentiate immune-related adverse events from infection. Immunohistochemical analysis revealed cytomegalovirus-positive cells, leading to the diagnosis of cytomegalovirus reactivation-associated duodenal ulcer. Treatment with ganciclovir improved both the symptoms and ulcers. In patients undergoing prolonged multiline immune checkpoint inhibitor-based therapy, cytomegalovirus reactivation after steroid treatment should be considered in the differential diagnosis of refractory upper gastrointestinal ulcers.

A man in his 70s with chronic hepatitis B carrier status was observed to have gradually enlarging hypervascular lesions in liver segments 6 and 8 during surveillance. Contrast-enhanced computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging revealed mild arterial-phase enhancement without definite washout, whereas positron emission tomography/CT demonstrated only mild fluorodeoxyglucose uptake. B-mode and contrast-enhanced ultrasonography (CEUS) did not reveal a clear Kupffer-phase defect; however, arterial-phase imaging showed homogeneous hyperenhancement accompanied by intratumoral vascular structures. Targeted biopsy of the arterial-phase-enhancing area enabled a definitive diagnosis. Histopathological examination demonstrated infiltration of small- to medium-sized lymphoid cells that were positive for CD20 and CD79a and negative for CD10, findings consistent with primary hepatic mucosa-associated lymphoid tissue lymphoma. In addition, numerous CD68-positive macrophages were identified within the lesion, potentially accounting for the absence of a Kupffer-phase defect. This case underscores the impact of intratumoral macrophages on imaging characteristics and supports the utility of arterial-phase CEUS-guided biopsy for diagnosis.

A 40-year-old woman with a 2-year history of ingesting health supplements to achieve weight loss presented to her primary care physician with generalized fatigue, and blood tests revealed severe hepatic dysfunction. At admission, following referral to our hospital for further examination, she was alert and reported no abdominal pain. Blood tests acute liver and renal failure accompanied by disseminated intravascular coagulation, whereas no findings suggested acute viral hepatitis or autoimmune liver diseases. Contrast-enhanced computed tomography revealed hepatomegaly, gallbladder atrophy, and gallbladder wall thickening. A drug lymphocyte stimulation test demonstrated strong positive reactions to health supplements including, spirulina and chlorella. The DDW-J2004 Drug-Induced Liver Injury Workshop score was 10 points, suggesting a diagnosis of hepatocellular-type drug-induced liver injury. Ischemic liver injury due to circulatory failure was an important differential diagnosis due to elevated brain natriuretic peptide and troponin I levels. Intravenous steroid administration improved liver and renal failure and disseminated intravascular coagulation. Consequently, the patient was discharged on the 28^th hospital day. The present case report highlights the importance of considering multiple contributing factors in the evaluation of liver failure. Although intensive care was life-saving, earlier improvement in interleukin-6 levels may predict potential recovery.

We report a case of duodenal bulb perforation occurring during treatment with atezolizumab plus bevacizumab for hepatocellular carcinoma in an 80-year-old woman. Upper gastrointestinal endoscopy before chemotherapy revealed no apparent ulcerative lesions in the esophagus, stomach, or duodenal bulb. She developed acute epigastric pain 14 days after the second treatment cycle. Computed tomography revealed the presence of intraperitoneal free air and fluid accumulation around the duodenal bulb, and emergency surgery was performed. A perforation, measuring approximately 2 mm in size, was identified on the anterior wall of the duodenal bulb and was closed by suturing. The perforation site was not histopathologically examined. Although the precise mechanism of perforation was uncertain, the clinical course did not suggest direct tumor invasion or immune-related enteritis. Instead, a bevacizumab-related mechanism, such as impairment of mucosal repair or microcirculatory impairment, was suspected. The present case illustrates that gastrointestinal perforation may occur even in patients without apparent pre-treatment ulcerative lesions.

Wilson disease is an autosomal recessive disorder of copper metabolism. Measurement of serum ceruloplasmin is important for the clinical management of Wilson disease. We report a patient with an unexpected serum ceruloplasmin value. A 41-year-old male had been treated for Wilson disease from childhood and was in a stable condition. His ceruloplasmin concentration had usually been approximately 2 mg/dL. On a medical examination day, his ceruloplasmin concentration was 32 mg/dL. His serum triglyceride concentration was 537 mg/dL. Serum ceruloplasmin was measured using nephelometry. Ultracentrifugation of the serum reduced the concentration of ceruloplasmin to 7 mg/dL. Chylous serum may affect the measured concentration of ceruloplasmin. Therefore, care should be taken when interpreting ceruloplasmin levels in the presence of elevated serum triglycerides.

Timely identification of patients with hepatitis C virus (HCV) antibody positivity is crucial for evaluation and referral. By repurposing a robotic process automation (RPA) tool already deployed for other hospital tasks, we reconstructed our workflow to integrate automated list generation into the existing multidisciplinary framework. Before implementation, laboratory technologists extracted records of HCV antibody-positive patients weekly from the data warehouse and manually entered them into a list. Following implementation, RPA automatically executed the data extraction function and generated the list daily. During the study period, 356 positive results were obtained from 15,506 HCV antibody tests. Manual transcription was eliminated, and a 1-month parallel comparison confirmed RPA–manual extraction concordance. Repurposing existing RPA resources may provide a low-burden approach to enhance hepatitis care workflows in community hospitals.