Although the fibrosis-4 (FIB-4) index is widely used for the noninvasive assessment of liver fibrosis, incorporating age into the index increases false-positive results in elderly patients. To address this limitation, we developed the fibrosis-3 (FIB-3) index, an age-independent score calculated using aspartate aminotransferase, alanine aminotransferase, and platelet count. In the derivation (n = 735) and validation (n = 324) cohorts, both including participants with metabolic dysfunction-associated steatotic liver disease, the diagnostic performance of the FIB-3 and FIB-4 indices was comparable (AUROC, 0.764 and 0.762, respectively), whereas the FIB-3 index reduced false-positive rates among older individuals. Subsequent studies in Japanese cohorts, including health screening and occupational populations, have expanded its potential research applications to hepatocellular carcinoma risk stratification, assessment of metabolic dysfunction-associated steatohepatitis and anemia risk, and comparison with serum glycan markers. This review summarizes the development and current evidence on the utility of the FIB-3 index.

Background: We evaluated a community-based referral pathway, the Liver Fibrosis Evaluation Program, in which primary care physicians measured mac-2 binding protein glycosylation isomer (M2BPGi) in patients with steatotic liver disease or diabetes and referred patients according to the results.

Methods: We retrospectively analyzed 108 cases of nonviral liver disease referred through this program since 2019. The referral threshold was M2BPGi ≥1.00 cutoff index. At a specialist hepatology center, vibration-controlled transient elastography (VCTE) was used to stratify patients into risk categories of <7.0, 7.0-11.0, or ≥11.0 kPa. The primary outcome was the occurrence of liver-related events.

Results: VCTE stratification identified 46 low-risk, 23 intermediate-risk, and 39 high-risk patients. After excluding hepatocellular carcinoma (HCC; n = 1) and intrahepatic cholangiocarcinoma (n = 1) detected at baseline, six liver-related events occurred during follow-up, all in the high-risk group (HCC, n = 4; esophageal varices, n = 2).

Conclusions: This two-step, community-linked pathway-M2BPGi screening in primary care followed by VCTE assessment at a specialist hepatology center-effectively identifies high-risk patients with steatotic liver disease and facilitate their management within a regional care network.

The present study aimed to reveal the prevalence of hepatitis C virus (HCV) infection caused by tattooing in Japan. The health examination records of all 465 prisoners detained in Miyagi Prison, Japan, as of May 12, 2025, were investigated. Among them, 90 had tattoos but no history of taking drug stimulants. Of these, 67 participated in this study. Only three participants, who received tattoos in 1966, 1974, and 1975, tested positive for HCV antibodies. While three of the 13 prisoners who were tattooed by 1975 were infected with HCV, none of the 54 prisoners who were tattooed after 1976 were infected. Since 1976, professional tattooists have reportedly stopped reusing tattooing ink and needles. However, 33.3% of the participants experienced ink-and-needle reuse; these individuals were tattooed by their acquaintances even after HCV detection.

A hepatitis C awareness campaign was delivered by care managers (CMs), targeting older adults requiring care and their family caregivers. Each CM received informational leaflets, a training video, and a test. Those who completed the video‑and‑test training were categorized as the education group (n = 89), with all others categorized as the non‑education group (n = 73). Participating CMs reported that 41 clients/family caregivers underwent hepatitis C virus (HCV) testing (education group: n = 15; non-education group: n = 26) with two individuals testing positive in the education group and one of them initiating treatment. Although testing rates were not notably different between the groups, the education group distributed more number of leaflets (mean: 16.8 vs. 12.8) and employed a broader range of messages (mean: 2.4 vs. 1.5). Testing was associated with leaflet quantity, message variety used, and the presence of specific messages offering free testing and oral treatment. Providing educational materials increased CM engagement and promoted behavioral improvements among clients/families. Therefore, CM involvement in HCV awareness campaigns may enhance the scope and efficacy of outreach activities.

A woman in her 60s with hepatocellular carcinoma (HCC) and sustained virological response following hepatitis C-related cirrhosis underwent multiple systemic treatments for metastatic disease, including immune checkpoint inhibitors (ICIs). In May (20xx+10), she developed epigastric pain 15 days following sorafenib initiation. Laboratory tests indicated increased serum amylase levels, and abdominal computed tomography revealed diffuse pancreatic enlargement with peripancreatic inflammation, leading to a diagnosis of acute pancreatitis.

Typical etiologies of pancreatitis were considered unlikely based on clinical history, laboratory findings, and imaging results. The patient's condition deteriorated despite discontinuing sorafenib and intensive conservative management. Considering the refractory clinical course and prior ICI exposure, immune-related pancreatic injury was considered in the differential diagnosis. On day 6 of hospitalization, steroid pulse therapy was initiated, causing rapid clinical, biochemical, and radiological improvements.

Although drug-induced pancreatitis associated with sorafenib remains a crucial consideration, this case suggests that immunological mechanisms related to previous ICI therapy can contribute to pancreatic injury, even after treatment discontinuation. In the era of sequential systemic therapy for HCC, clinicians should consider immune-related pancreatic disorders in the differential diagnosis of pancreatitis, particularly in severe or treatment-refractory cases.

Spontaneous fungal peritonitis (SFP) is a rare but highly fatal complication in patients with decompensated liver cirrhosis. Herein, we present a case of SFP complicating decompensated alcoholic liver cirrhosis. A man in his 70s with decompensated alcoholic liver cirrhosis had undergone repeated paracentesis for refractory ascites and had a recent history of spontaneous bacterial peritonitis. He was admitted to the hospital with fever, abdominal distension, and lower extremity edema. Laboratory findings revealed elevated inflammatory markers and Child-Pugh class C liver dysfunction. Abdominal ultrasonography demonstrated massive ascites with septated, fibrin-like structures. Although antibacterial therapy was initiated for suspected spontaneous bacterial peritonitis, there was limited clinical response. Subsequent fungal culture of the ascitic fluid detected Candida albicans, leading to a diagnosis of SFP. Antifungal therapy was initiated, and the regimen was eventually changed to an echinocandin based on susceptibility tests, resulting in gradual clinical improvement. The findings of this case emphasize the need for considering SFP in patients with cirrhosis who respond poorly to antibacterial therapy and exhibit multiple risk factors.

A woman in her 80s underwent surgical resection for hepatocellular carcinoma (HCC) in liver segments 6/7 and developed repeated intrahepatic recurrences, treated with transcatheter arterial chemoembolization and radiofrequency ablation. Three years later, disease progression with multiple intrahepatic and pulmonary metastases was observed, and combination therapy with atezolizumab plus bevacizumab was initiated. The second cycle was postponed after the first administration due to COVID-19 infection. Nevertheless, follow-up computed tomography performed before the second cycle demonstrated complete disappearance of intrahepatic lesions and pulmonary metastases. Furthermore, serum levels of alpha-fetoprotein and protein induced by vitamin K absence-II normalized, and the overall response was assessed as complete according to RECIST version 1.1. The patient remained recurrence-free and experienced no treatment-related adverse events during follow-up. Complete response is rare in advanced HCC with multiple intrahepatic lesions and pulmonary metastases after locoregional therapy followed by atezolizumab plus bevacizumab. This report presents a clinically crucial case of early deep response achieved in this setting.

Hepatitis B virus (HBV) persists in hepatocyte nuclei as covalently closed circular DNA (cccDNA), whose transcriptional activity is regulated by epigenetic modifications. Although cccDNA can remain transcriptionally suppressed in patients who are HBV surface antigen-negative and anti-HBV core antibody-positive, HBV reactivation may occur following immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation. Valemetostat, a selective EZH1/2 inhibitor approved for relapsed or refractory adult T-cell leukemia/lymphoma, may impact the epigenetic regulation of HBV cccDNA; however, its role in HBV reactivation remains unclear. Here, we present two patients with adult T-cell leukemia/lymphoma who received valemetostat after undergoing hematopoietic stem cell transplantation and experienced increases in HBV DNA levels. One patient with previously resolved HBV infection experienced HBV reactivation, whereas the other patient, an HBV carrier receiving tenofovir therapy, experienced an increase in HBV DNA levels.

Prompt identification and treatment of hepatitis C virus (HCV) infection are crucial for preventing progression to advanced liver disease, including hepatocellular carcinoma. However, some patients with initially positive anti-HCV antibodies do not receive appropriate evaluation or referral to specialists. To overcome this issue, we developed and evaluated a case-finding system led by medical clerks, a type of nonmedical staff, certified as Hepatitis Medical Coordinators. The clerks identified patients with initially positive anti-HCV antibodies from infection control reports, excluded cases not requiring referral, and notified the ordering departments. Subsequently, physicians explained the results and recommended referral to a gastroenterologist. The nonreferral rate before implementation (2017-2018) was 40%-41%, which decreased to 11%-23% following implementation (2019-2021). This clerk-led system effectively enhanced referral to gastroenterology.