Mirjam Kolev

Background & Aims: The distinction of drug‐induced liver injury (DILI), drug‐induced autoimmune‐like hepatitis (DI‐ALH), and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker in AIH. This retrospective study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI‐ALH, and DILI and thus identify patients in need of immunosuppression. Methods: Samples from 120 patients (AIH = 81, DI‐ALH = 16, DILI = 23) were compared to a control group (non‐AIH‐non‐DILI‐liver disease = 596 and healthy controls = 190). Results: No patient in the DILI‐group but 98% in the AIH‐ and 94% in the DI‐ALH‐group received immunosuppressive treatment. PIgG levels were significantly higher in the AIH‐group 1.9 normalised arbitrary units (nAU) compared to DILI (1.1 nAU, p < 0.001), non‐AIH‐non‐DILI‐LD (1.0 nAU, p < 0.001) and healthy controls (0.27 nAU, p < 0.001). PIgG levels for DI‐ALH (1.7nAU) were significantly higher compared to DILI ( p = 0.044) and non‐AIH‐non‐DILI‐LD and healthy controls (both p < 0.001). Highest AUC was seen for pIgG (0.818) compared to conventional autoantibodies. The overall accuracy of pIgG to distinguish AIH from DILI (74%) and liver injuries with and without the need for immunosuppression (73%) was like that of ANA (71%/73%) and SMA (74%/69%) at cut‐offs of ≥ 1/40. PIgG was positive in up to 79% of patients with AIH that were negative for a conventional autoantibody and was positive in 90% of DI‐ALH cases compared to 25% in DILI that were caused by the same drugs. Conclusions: PIgG may complement current serologic tests to identify patients with liver injury in need of immunosuppressive treatment.

BACKGROUND AND AIMS: Bulevirtide 2 mg/day was approved in Switzerland in February 2025 for the treatment of chronic hepatitis D virus (HDV) infection. We present real-world data on efficacy and safety in patients treated under an early access programme. METHODS: This retrospective, multicentre Swiss cohort study included patients with compensated HDV-associated cirrhosis in whom bulevirtide therapy (2 mg/day) was initiated between January 2020 and August 2024 under a compassionate use programme. Virological response was defined as a HDV RNA level that was undetectable or declined ≥2 log10 IU/ml from baseline. Biochemical response was defined as normalisation of ALT. Combined response was defined as achieving both virological and biochemical response. Liver-related events and adverse events were assessed. RESULTS: Fourteen patients with compensated HDV-related cirrhosis received bulevirtide for a median duration of 1.85 years (1.1–2.1). Median age was 51.3 years (43.9–58.5), and 71.4% were men. Baseline ALT was 81 U/l (55.8–88.8), platelet count 102.5 × 109/l (67.3–141.3) and liver stiffness 15.3 kPa (11.8–22.1). Baseline HDV RNA was 4.82 log10 IU/ml (4.52–6.23). Biochemical, virological and combined responses were observed in 50%, 64.3% and 35.7% at 6 months; 66.7%, 75% and 58.3% at 12 months; and 62.5% for all three response types at 24 months. Two patients (14.3%) developed de novo hepatocellular carcinoma, and one (7.14%) patient underwent liver transplantation. No serious adverse events were reported. Mild transient pruritus occurred in two (14.3%) patients. CONCLUSIONS: In this real-world cohort of patients with compensated HDV cirrhosis, bulevirtide demonstrated favourable efficacy and safety. These findings support the integration of bulevirtide into routine care for patients with HDV and compensated cirrhosis in Switzerland following its reimbursement status as of 2025. Longer-term follow-up is warranted to assess the impact on liver-related outcomes.

BACKGROUND AND AIM OF THE STUDY: For many years, the standard treatment following liver transplantation for hepatitis B has been a combination of hepatitis B immunoglobulin and nucleos(t)ide analogues such as entecavir and tenofovir. However, because of the high costs and logistical challenges of long-term hepatitis B immunoglobulin use, alternative approaches such as vaccination and hepatitis B immunoglobulin-free regimens are being explored. This study gathered information on a potential response (or lack thereof) and addressed the adverse events associated with active immunisation in liver transplant recipients in a Swiss cohort with hepatitis B virus (HBV)-related diseases after discontinuing hepatitis B immunoglobulin. METHODS: Participants were recruited at the University Hospital of Bern between January 2022 and December 2023. Eligibility was restricted to liver transplant recipients with HBV-related disease who were receiving hepatitis B immunoglobulin and nucleos(t)ide analogue therapy at the time of study entry. The primary outcome was HBV relapse following hepatitis B immunoglobulin discontinuation; secondary outcomes included the response rate to active immunisation and reported adverse events. After exclusion, 18 patients were analysed. These patients, under ongoing immunosuppression and antiviral nucleos(t)ide analogue therapy, received active immunisation a minimum of 4 weeks after stopping hepatitis B immunoglobulin. Blood samples were collected at baseline and 4 weeks after vaccination, with follow-up extending for at least 12 months. Responders were defined as those with anti-HB levels of >10 IU/l. All patients received at least three vaccinations. RESULTS: Six patients responded to the active immunisation with anti-HBs development, showing a response rate of 33.3%. No side effects or HBV recurrence were reported during the study period. CONCLUSION: In this cohort, following liver transplantation for hepatitis B, patients who discontinued hepatitis B immunoglobulin while continuing nucleos(t)ide analogue therapy showed no relapse of hepatitis B, and a double-dose vaccination regimen yielded a modest response rate. These findings warrant further investigation into optimising vaccination strategies in this population.

Background and Aim: Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy‐1, an adhesion molecule detected as soluble Thy‐1 (sThy‐1) in serum, is primarily expressed by portal myofibroblasts (PMF) and, to a lesser extent, hepatic stellate cells (HSC), serving as a marker for myofibroblast activity in liver pathology. This study aimed to elucidate the correlation between Thy‐1 expression in liver histology and sThy‐1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction‐associated steatotic liver disease (MASLD).Methods: Liver histology samples were stained for Thy‐1, and sThy‐1 was measured using an enzyme‐linked immunosorbent assay (ELISA).Results: In patients with PBC and MASLD, an association between portal Thy‐1 expression and the extent of fibrosis was observed. Notably, while sinusoidal Thy‐1 expression aligned with fibrosis severity in PBC (p < 0.001), this association was not statistically significant in MASLD (p = 0.059). Moreover, variations in soluble Thy‐1 levels paralleled the progression from mild to advanced fibrosis stages in PBC.Conclusions: Thy‐1 expression levels were associated with the severity of fibrosis, which could support its role in monitoring the presence and activity of myofibroblasts in liver diseases.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p