自己免疫性肝炎

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often requires intensive care and rapid escalation of immunotherapy. We report a critically ill woman with refractory anti-NMDAR encephalitis treated with tocilizumab (TCZ) as early second-line therapy and discuss the rationale for IL-6 receptor blockade over other treatment strategies. CASE REPORT: A previously healthy 30-year-old woman developed psychosis, catatonia, dyskinesias, and refractory status epilepticus; anti-NMDAR antibodies were detected in the CSF using a commercial fixed cell-based assay. She required mechanical ventilation and received methylprednisolone and IVIG 35 days after symptom onset, without improvement. The course was complicated by sepsis, dialysis-dependent acute kidney injury, anemia, and thrombocytopenia. Given active infection, cytopenias, and prior hepatitis B exposure, TCZ was initiated with tenofovir prophylaxis. Over the subsequent 30 days, she improved, was extubated, and became seizure-free. Rituximab (RTX) was started 9 months after onset. At 25-month follow-up, outcomes were mRS 2, CASE 1, and MoCA 26/30. CONCLUSION: This case describes rapid clinical improvement temporally associated with TCZ administration in a critically ill patient with refractory anti-NMDAR encephalitis. Although causality cannot be established, TCZ may offer a rapid and time-limited immunomodulatory option for carefully selected ICU patients when conventional second-line therapies are unsuitable. Prospective controlled studies are required to determine its efficacy and optimal timing.

BACKGROUND & AIMS: Patients with chronic liver disease (CLD) frequently develop reduced bone mass and an increased risk of fragility fractures, making osteoporosis a major extrahepatic complication that affects long-term prognosis and quality of life. Although the association between CLD and osteoporosis is well recognized, epidemiological risk factors and the shared versus etiology-specific mechanisms remain incompletely integrated. Current clinical risk assessment relies largely on bone mineral density, which fails to capture microarchitectural deterioration and may underestimate true fracture risk. This review aimed to integrate current epidemiological and mechanistic evidence and examine emerging approaches to precision prevention and management of CLD-related osteoporosis. METHODS: We reviewed relevant literature published between 2000 and 2025 identified through PubMed, Embase, and Web of Science, prioritizing high-quality clinical, translational, and basic research studies. The review focused on four major CLD populations: chronic hepatitis B, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and autoimmune hepatitis. RESULTS: Evidence supports a multifactorial pathogenesis involving inflammation, endocrine-metabolic dysregulation, and disturbances in the liver-bone and liver-gut-bone axes, which collectively promote osteoclast-osteoblast imbalance and bone loss. Based on these mechanistic insights, we propose a risk-stratified screening and dynamic monitoring framework that emphasizes multidimensional evaluation using bone quality assessment and emerging biomarkers. Individualized prevention and treatment strategies are discussed according to disease etiology and risk profiles, with particular attention to emerging therapeutic directions such as bone-targeted drug delivery and cross-organ metabolic regulation. CONCLUSIONS: Collectively, this review provides a conceptual and translational framework to support precision prevention and management of osteoporosis in patients with chronic liver disease. IMPACT AND IMPLICATIONS: Patients with chronic liver disease (CLD) face a markedly increased risk of osteoporosis and fragility fractures, but this systemic complication remains insufficiently recognized, while conventional assessment based mainly on bone mineral density may underestimate clinically relevant alterations in bone quality and microarchitecture. By synthesizing epidemiological data and both shared and etiology-specific mechanisms across chronic hepatitis B, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and autoimmune hepatitis, this review offers an integrated framework for hepatologists, endocrinologists, and translational researchers. The findings underscore the value of risk-stratified screening, dynamic assessment of bone quality and biomarkers, and individualized preventive and therapeutic strategies to optimize skeletal health in patients with CLD. However, because a substantial proportion of the mechanistic evidence remains preclinical, these translational implications should be interpreted cautiously and require confirmation in well-designed prospective multicenter studies prior to widespread implementation.

Chronic liver diseases (CLD) is a broad term, which includes alcoholic and metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, autoimmune and many other conditions. CLDs can progress to fibrosis, and hepatocellular carcinoma (HCC) and is a major global health burden. Immune cells play a critical, yet often complex role in the initiation, progression, and resolution of liver injury. While traditional methods have elucidated many aspects of immune cell function during liver disease, advanced imaging techniques are now providing unprecedented spatio-temporal insights into immune cell dynamics in vivo, revealing new contributions and interactions. This review will explore the capabilities of advanced intravital microscopy, in visualizing and characterizing the diverse populations of immune cells within the liver microenvironment during CLD. Understanding the many roles immune cells play through imaging opens new possibilities to identify diagnostic biomarkers and therapeutic strategies for CLD treatment.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease lacking noninvasive biomarkers that adequately reflect disease status. CD161 is an immunoregulatory molecule expressed on T and NK cells, but its soluble (sCD161) and membrane-bound (mCD161) forms remain poorly characterized in PBC. We measured serum sCD161 and cellular mCD161 in patients with PBC, patients with post-hepatitis B cirrhosis (PHBC), and healthy controls (HCs), and examined CD161 expression in a PBC mouse model. Serum sCD161 was markedly elevated in patients with PBC compared with both patients with PHBC and HCs. It correlated positively with the Mayo score, total bilirubin, direct bilirubin, and red cell distribution width and negatively with apolipoprotein A1, albumin, and platelet count. ROC analysis yielded an AUC of 0.8851, with 80.88% sensitivity and 86.79% specificity. The AUC for sCD161 was numerically higher than that for GGT but slightly lower than that for ALP. In contrast, mCD161 expression was reduced across multiple peripheral T-cell subsets. CD161 mRNA levels remained unchanged, whereas ADAM10/17 inhibition reduced sCD161 release and increased cell-surface mCD161 expression, supporting a role for proteolytic shedding in these reciprocal alterations. Reduced CD161 expression was also observed in T-cell subsets from the liver and spleen of PBC model mice, and multiplex immunofluorescence showed fewer hepatic CD4⁺CXCR5⁺CD161⁺ cells. These findings support the potential of sCD161 as an adjunctive biomarker for PBC diagnosis and disease assessment.

The present study reported the case of a 48-year-old female who developed drug-induced autoimmune-like hepatitis (DI-ALH) during adjuvant oxaliplatin, 5-fluorouracil and leucovorin calcium (FOLFOX) therapy for rectal cancer. The initial liver injury was attributed to non-specific chemotherapy-associated hepatotoxicity, resulting in a delay in the correct diagnosis. Recurrent transaminitis following oxaliplatin rechallenge subsequently suggested an immune-mediated mechanism. A clinical pharmacist played a central role in the multidisciplinary team by leading the causality assessment and developing an individualized corticosteroid management strategy, which enabled completion of all 12 planned cycles of FOLFOX without severe hepatic flares. Liver enzyme levels normalized following completion of chemotherapy and remained stable after glucocorticoid discontinuation during 12 months of follow-up. The present case report highlighted that DI-ALH may closely resemble idiopathic autoimmune hepatitis but typically resolves after withdrawal without the need for long-term immunosuppressive therapy. It also underscored the important contribution of clinical pharmacists in the recognition, assessment and management of complex chemotherapy-associated toxicities.