Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.

The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease. To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren's disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland. In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren's disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time. Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment. While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited. To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH. Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up. Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment. Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control. Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.

Clear guidance is needed in the development and implementation of laboratory biomarkers in medicine. So far, no standardized phased approach is established that would pilot researchers and clinicians in this process. This leads to often incompletely validated biomarkers, which can bear the consequence of wrong applications, misinterpretation and inadequate management in the clinical context.

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.