New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review

Abstract

Background Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. Objectives To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. Methods For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. Results Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. Conclusion Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.

Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis

“…Similar findings have been reported in two systematic reviews of vaccine-associated liver disease [ 32 , 34 ] (Table 2 ). In the largest review, an acute hepatitis with autoimmune features had developed within 7–21 days (median, 14 days) after vaccination in 138 patients; 98% had received mRNA-based vaccines against SARS-CoV-2; most patients had been treated with immunosuppressive drugs; 89% had achieved full recovery; and 2.2% had died [ 32 ].…”

“…Similar findings have been reported in two systematic reviews of vaccine-associated liver disease [ 32 , 34 ] (Table 2 ). In the largest review, an acute hepatitis with autoimmune features had developed within 7–21 days (median, 14 days) after vaccination in 138 patients; 98% had received mRNA-based vaccines against SARS-CoV-2; most patients had been treated with immunosuppressive drugs; 89% had achieved full recovery; and 2.2% had died [ 32 ]. In the smaller review involving 32 patients who had developed an autoimmune hepatitis-like disease after vaccination, 7 improved spontaneously (22%); 24 of the 25 treated patients improved or resolved (96%); and one patient died (3%) [ 34 ].…”

Inflammatory and vascular biomarkers in post‐COVID‐19 syndrome: A systematic review and meta‐analysis of over 20 biomarkers

“…A meta‐analysis calculated that vaccinated individuals (against COVID‐19) had a 29% lower relative risk of developing PCS compared to unvaccinated individuals, with subgroup analyses showing that this effect remained with vaccination before or after COVID‐19 75 . Despite the known risks of COVID‐19 vaccines (e.g., mRNA vaccine‐related myocarditis and DNA vaccine‐related thrombotic thrombocytopaenia), current consensus agrees that the overall risk‐benefit ratio still favours the benefit 76–80 . Furthermore, in light of the increase in certain immune and vascular biomarkers in PCS found in our meta‐analysis, therapies targeting these biomarkers may hold potential for treating PCS.…”

Immune-mediated liver injury following COVID-19 vaccination

“…The mean duration between receiving the first or second vaccine dose and subsequent onset of liver injury was 17.3 (11.2–23.4) days and was mostly associated with mRNA vaccines, possibly to their stronger immunogenic potency[ 20 ]. The presence of underlying autoimmune diseases ( e.g , Hashimoto thyroiditis, primary sclerosing cholangitis) is evident in approximately 25% of patients and could explain temporal and spatial differences in manifestations and prevalence, respectively, according to genetic predispositions[ 22 ]. Antinuclear antibody (ANA) was by far the most prevalent autoantibody, followed by spinal muscular atrophy and anti-myocardial antibody (AMA), resembling a type 1 AIH pattern.…”