Summary Background The incidence of elevated liver chemistries and the presence of pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19. Aims To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19. Methods A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19. Results 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P < 0.001]) and severe disease (OR‐2.87 [95% CI, 2.29‐3.6, P < 0.001]) compared to patients without elevated liver chemistries. Conclusions Elevated liver chemistries are common at presentation and during COVID‐19. The severity of elevated liver chemistries correlates with the outcome of COVID‐19. The presence of CLD does not alter the outcome of COVID‐19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.

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.

Background: Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. Methods: The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality. Findings: Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60¢38 (5¢24) years, and 68¢5% were men. The mean time (SD) to COVID-19 infection was 5¢72 (1¢75) years. Based on 17 studies (I 2 = 7¢34) among 1,481 LT recipients, the cumulative incidence of mortality was 17¢4% (95% confidence interval [CI], 15¢4À19¢6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0¢8 [0¢6À1¢08]; P = 0¢14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1¢5 [0¢63À3¢56]; P = 0¢35). The cumulative incidence of graft dysfunction was 2¢3% (1¢3À4¢1). Nearly 23% (20¢71À25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55¢9% (38¢1À72¢2) patients after COVID-19 infection. Interpretation: LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

Vasoactive drugs form the mainstay of therapy for two of the most important complications of liver disease: hepatorenal syndrome (HRS) and acute variceal bleed (AVB). With cumulative evidence supporting the use in cirrhosis, terlipressin has been recommended for the management of HRS and AVB. However, owing to the safety concerns, terlipressin was not approved by food and drug administration (FDA) until now. In this review, we discuss the pharmacology and the major practice‐changing studies on the safety and efficacy of terlipressin in patients with cirrhosis particularly focusing on existing indications like AVB and HRS and reviewing new data on the expanding indications in liver disease. The references for this review were identified from PUBMED with MeSH terms such as “terlipressin,” “hepatorenal syndrome,” “varices, esophagal and gastric,” “ascites” and “cirrhosis.” Terlipressin, a synthetic analogue of vasopressin, was introduced in 1975 to overcome the adverse effects of vasopressin. Terlipressin is an effective drug for HRS reversal in patients with liver cirrhosis and acute‐on‐chronic liver failure. There is documented mortality benefit with terlipressin therapy in HRS and AVB. Adverse effects are common with terlipressin and need to be monitored strictly. There is some evidence to support the use of this drug in refractory ascites, hepatic hydrothorax, paracentesis‐induced circulatory dysfunction and perioperatively during liver transplantation. However, terlipressin is not yet recommended for such indications. In conclusion, terlipressin has stood the test of time with expanding indications and clear prerequisites for clinical use. Our review warrants a fresh perspective on the efficacy and safety of terlipressin.

COVID‐19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID‐19 pandemic. Although it is suggested to wait for 4 weeks after COVID‐19 infection, there are no data to support or refute the timing of liver transplant after COVID‐19 infection. Here we describe the course and outcomes of COVID‐19‐infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase‐polymerase chain reaction (RT‐PCR) positive for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID‐19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID‐19 infection.