Liver cirrhosis causes various complications due to impaired hepatocellular function and altered hepatic blood flow, resulting in reduced quality of life and a poorer prognosis. The management of hepatic encephalopathy represents an essential component of clinical care. Ammonia is significantly involved in the pathophysiology of hepatic encephalopathy, and blood ammonia measurement is valuable for diagnosis; however, disease severity correlates more closely correlated with arterial than with venous ammonia levels. This finding may reflects the fact that the brain is perfused by arterial blood, in which ammonia concentrations are higher.

Covert hepatic encephalopathy, which lacks overt clinical symptoms but can be detected using neuropsychological testing, has recently garnered increasing attention. Compared with overt hepatic encephalopathy, the association between covert hepatic encephalopathy and blood ammonia levels appears weaker, likely because venous ammonia levels, rather than arterial ammonia levels, are frequently assessed.

This article reviews the role of ammonia in the pathophysiology of liver cirrhosis, with a focus on hepatic encephalopathy.

The elimination of hepatitis C virus (HCV) requires strategies to identify undiagnosed carriers who cannot be reached by conventional screening. In a rural Japanese cohort of 5,027 adults, we implemented an opt-out approach through routine health checkups and clinic visits and an opt-in approach using a mail-in questionnaire survey. Between June 2021 and March 2024, 3,121 residents (62.1%) underwent HCV antibody testing, including 1,112, 1,461, and 548 individuals tested in clinics, during health checkups, and in response to the questionnaire survey, respectively. Among 2,451 unscreened residents, 1,071 (43.7%) returned the questionnaire. Although awareness of the free screening program was limited (32.2%), willingness to be tested was high (64.8%), particularly among younger adults. The overall screening rate improved from 51% to 62.1% by incorporating the mail-in questionnaire survey. These findings suggest that combining conventional health service-based screening with a mailed opt-in questionnaire survey is an effective strategy for detecting individuals who have not been reached and may facilitate regional HCV micro-elimination in Japan.

We implemented a mailed notification program for reconnecting individuals who tested positive for viral hepatitis, who were either undiagnosed or diagnosed but untreated, with medical care. Between July 2015 and March 2024, 419 patients with positive viral hepatitis results but no documented test report were identified. Following medical record review and exclusions, 53 patients (33 HBsAg-positive and 20 anti-HCV-positive) were selected for notification. Each letter included test results, general information on viral hepatitis, and guidance on accessing care and was mailed in June 2024. The response rate was 36% (19/53), and 19% of the patients (10/53) successfully reengaged in medical care or treatment. These findings suggest that institutional support via mailed notifications can contribute to promoting reengagement in care and achieving micro-elimination of hepatitis at the regional level.

A 66-year-old woman with stage IV hormone receptor-positive breast cancer developed severe liver injury following the initiation of abemaciclib (a CDK4/6 inhibitor) in combination with letrozole. Repeated improvement and relapse occurred upon discontinuation and reintroduction of abemaciclib. Despite permanent withdrawal of the drug, her AST and ALT levels increased to 1744 U/L and 1199 U/L, respectively. Based on her clinical course, drug-induced autoimmune-like hepatitis (DI-ALH) secondary to abemaciclib was suspected. Treatment with prednisolone (30 mg/day) led to a rapid reduction in hepatobiliary enzyme levels. After discharge, corticosteroids were gradually tapered and discontinued. The patient subsequently received palbociclib, another CDK4/6 inhibitor, without recurrence of liver injury. DI-ALH should be considered when liver injury develops during abemaciclib therapy and does not resolve after drug cessation. Corticosteroid therapy is effective for DI-ALH, and breast cancer treatment may continue safely with an alternative CDK4/6 inhibitor.

We report a rare case of simultaneous immune-related polyarthritis and hyperbilirubinemia occurring during combination therapy with atezolizumab and bevacizumab for hepatocellular carcinoma.

A man in his 70s with a history of hepatitis C cirrhosis achieving a sustained virologic response developed acute symmetrical polyarthritis in his limbs during his 12th course of immunotherapy. Given this patient's medical history, psoriatic arthritis was initially suspected. Steroid therapy was initiated based on orthopedic evaluation, resulting in prompt symptom relief.

Retrospective assessment of the clinical course and serologic findings suggested immune-related arthritis.

During the patient's 13th course, he experienced fatigue with a marked increase in total bilirubin (10.09 mg/dL). Imaging showed no biliary obstruction, and other hepatic causes were excluded.

Steroid therapy was again administered, leading to gradual improvement in liver function.

This case underscores the importance of recognizing simultaneous immune-related adverse events involving multiple organs, particularly in patients with underlying autoimmune conditions. Early diagnosis and steroid intervention might improve outcomes.

A female in her 50s developed a fever and right flank pain two months after undergoing surgery for peritonitis due to a perforated Meckel's diverticulum at another hospital. Laboratory tests and computed tomography revealed a liver abscess; however, antibiotic therapy was ineffective, and drainage was difficult because no liquefied component was observed. Liver biopsy revealed hepatic inflammatory pseudotumor (HIPT). Although symptoms temporarily improved, they recurred three months later, and a new lesion appeared in another hepatic segment, resulting in referral to our hospital. Imaging demonstrated a solid lesion, and a repeat biopsy confirmed the same diagnosis. Regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs) caused transient improvement; however, recurrence occurred one month later with necrosis within the lesion. Aspiration confirmed the presence of pus, and drainage with antibiotic therapy led to clinical and radiological improvement. This case suggests that NSAIDs can improve inflammation secondary to HIPT-induced by peritonitis.

Hepatocellular carcinoma (HCC) originating in a nonfibrotic liver without established risk factors is relatively rare, especially in very elderly individuals. We report a case of HCC in a male in his 90s that was incidentally detected using computed tomography. Histological examination revealed an Edmondson grade III HCC in the right hepatic lobe, whereas the nontumorous liver tissue showed neither fibrosis nor inflammatory changes (A0/F0).

Paired tumor and nontumor liver tissue whole-exome sequencing identified 3,430 single-nucleotide variants and 457 insertions/deletions. Among cancer-related genes, somatic mutations were detected in 16 genes; however, only a missense mutation in TP53 (p. G245V; NM_000546.6:c.734G>T) corresponded to a known HCC-associated hotspot mutation. Other major driver genes, including the TERT promoter, CTNNB1, or ARID1A, exhibited no alterations.

Although whole-exome sequencing poses limitations in assessing noncoding regions and certain copy number alterations, these findings suggest that TP53 dysfunction may have influenced hepatocarcinogenesis in this case. Furthermore, age-related hepatocyte senescence, declining immune surveillance, and other aging-associated biological factors likely contributed to tumor development.

This case underscores the occurrence of HCC in a very elderly patient without evident underlying liver disease and offers clinical insight into hepatocarcinogenesis in older adults, warranting further accumulation and investigation of similar cases.

A 60-year-old man was referred to our hospital for treatment of a 13.5 cm hepatocellular carcinoma occupying the right lobe and tested positive for anti-hepatitis C virus (HCV) antibodies. The patient was diagnosed with unresectable hepatocellular carcinoma and underwent three courses of combination therapy with tremelimumab and durvalumab, followed by transcatheter arterial embolization, resulting in significant tumor reduction. Subsequently, he developed liver injury, which was considered to be an immune-mediated adverse event, and was treated with steroids and immunosuppressive drugs without improvement. Hepatic function rapidly normalized after the initiation of glecaprevir and pibrentasvir therapy for HCV infection, and the patient continued treatment without recurrence of hepatic injury after tapering off steroids and immunosuppressive drugs and resuming durvalumab therapy. Acute exacerbation of chronic HCV infection and immune-mediated adverse events should be considered as potential causes of liver injury in patients with HCV infection.

This study investigated the distribution of hepatitis B virus (HBV) genotypes in western Shikoku, Japan, particularly focusing on genotype D. We retrospectively analyzed 707 HBsAg-positive patients who underwent HBV genotyping from 2011 to 2024. Patients were stratified by age: < 40, 40-49, 50-59, and ≥60 years. Genotype D was observed in 20%-30% of patients aged 40-59 years, but only 3.7% in those aged < 40 years, demonstrating the influence of perinatal transmission prevention and public health initiatives. Conversely, 1.6%-7.0% of younger generations had genotype A, raising concerns owing to its higher risk of chronicity following horizontal infection. These findings suggest that although the prevalence of genotype D infections has significantly declined, ongoing surveillance and awareness campaigns remain essential for controlling genotype A transmission.

The fibrosis-4 index (FIB-4) is recommended as a first-line screening tool for advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. We analyzed 118,556 blood test samples from 48 primary care facilities to evaluate the determinants of age-related changes in the FIB-4. We found that FIB-4 progressively increased with age, largely driven by an age-associated decline in platelet counts. The proportion of samples exceeding the high-risk FIB-4 cutoff (≥2.67) significantly increased with advancing age, surpassing 30% in individuals aged ≥80 years. Alanine aminotransferase levels declined in older patients and contributed minimally to FIB-4 elevation. Platelet count exhibited the strongest association with elevated FIB-4 across age strata. These findings indicate that the age-related reduction in platelet count may inflate high-risk classifications when FIB-4 is broadly applied for advanced fibrosis screening in aging populations.