Background and Aims A few case reports of autoimmune hepatitis–like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS‐CoV‐2 vaccination in a large case series. Approach and Results We collected data from cases in 18 countries. The type of liver injury was assessed with the R‐value. The study population was categorized according to features of immune‐mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18–79) years at presentation. Liver injury was diagnosed a median 15 (range: 3–65) days after vaccination. Fifty‐one cases (59%) were attributed to the Pfizer‐BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford‐AstraZeneca (ChAdOX1 nCoV‐19) vaccine and 16 (18%) cases to the Moderna (mRNA‐1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune‐mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3–4 liver injury than for grade 1–2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune‐mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow‐up. Conclusions SARS‐CoV‐2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune‐mediated features or severe hepatitis. Outcome was generally favorable, but vaccine‐associated liver injury led to fulminant liver failure in one patient.

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The novel mRNA-based vaccines against SARS-CoV-2 display encouraging safety and efficacy profiles. However, there is a paucity of data regarding their immunogenicity and safety in patients with liver diseases (PWLD), especially in those with cirrhosis. We prospectively assessed anti-SARS-CoV-2 S-spike IgG antibodies and neutralizing activity in fully vaccinated PWLD (n = 87) and controls (n = 40). Seroconversion rates were 97.4% (37/38) in cirrhotic PWLD, 87.8% (43/49) in non-cirrhotic PWLD and 100% (40/40) in controls. Adequate neutralizing activity was detected in 92.1% (35/38), 87.8% (43/49) and 100% (40/40) of cirrhotics, non-cirrhotics and controls, respectively. On multivariable analysis, immunosuppressive treatment was negatively correlated with anti-SARS-CoV-2 antibody titers (coefficient (SE): −2.716 (0.634), p < 0.001) and neutralizing activity (coefficient (SE): −24.379 (4.582), p < 0.001), while age was negatively correlated only with neutralizing activity (coefficient (SE): −0.31(0.14), p = 0.028). A total of 52 responder PWLD were reassessed approximately 3 months post-vaccination and no differences were detected in humoral responses between cirrhotic and non-cirrhotic PWLD. No significant side effects were noted post vaccination, while no symptomatic breakthrough infections were reported during a 6-month follow up. Overall, our study shows that m-RNA-based SARS-CoV-2 vaccines are safe and efficacious in PWLD. However, PWLD under immunosuppressive treatment and those of advanced age should probably be more closely monitored after vaccination.

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. It is strongly associated with obesity, type 2 diabetes (T2DM), and other metabolic syndrome features. Reflecting the underlying pathogenesis and the cardiometabolic disorders associated with NAFLD, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has recently been proposed. Indeed, over the past few years, growing evidence supports a strong correlation between NAFLD and increased cardiovascular disease (CVD) risk, independent of the presence of diabetes, hypertension, and obesity. This implies that NAFLD may also be directly involved in the pathogenesis of CVD. Notably, liver sinusoidal endothelial cell (LSEC) dysfunction appears to be implicated in the progression of NAFLD via numerous mechanisms, including the regulation of the inflammatory process, hepatic stellate activation, augmented vascular resistance, and the distortion of microcirculation, resulting in the progression of NAFLD. Vice versa, the liver secretes inflammatory molecules that are considered pro-atherogenic and may contribute to vascular endothelial dysfunction, resulting in atherosclerosis and CVD. In this review, we provide current evidence supporting the role of endothelial cell dysfunction in the pathogenesis of NAFLD and NAFLD-associated atherosclerosis. Endothelial cells could thus represent a “golden target” for the development of new treatment strategies for NAFLD and its comorbid CVD.