The Lasting Effects of COVID‐19 on The Progression of Non‐Alcoholic Fatty Liver Disease

Abstract

It is estimated that around 30% of the Western population has non‐alcoholic liver disease (NAFLD); a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression towards inflammation and irreversible fibrosis (non‐alcoholic steatohepatitis, or NASH). With inflammation being a key component of the transition to NASH, it raises the question of whether the ongoing COVID‐19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of NAFLD. Specifically, it remains unclear if potential chronic sequelae of COVID‐19 in recovered patients may increase predisposition for NASH. Since NASH maintains a high risk for hepatocellular carcinoma, liver failure, and need for liver transplant, potential additive effects of COVID‐19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID‐19 could have chronic sequelae that affect the progression of NAFLD pathogenesis. It was hypothesized that severe cases of COVID‐19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes of the liver, similar to those seen in NASH.A scoping review of literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug‐induced liver injury, and hypoxia seen in COVID‐19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of NAFLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, GIT, portal system, or systemic circulation.Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes was unlikely, but direct viral insult of cholangiocytes was a potential complication. High serum levels of IL‐1, TNF‐a, and MCP‐1, in COVID‐19 were found as potential risk factors for NASH development. Hypoxia, altered lipid metabolism, and iatrogenic drug‐induced liver injury were also proposed as potential precipitators of NASH development. Notably, lasting changes in gut microbiome were also frequently observed, and correlate closely with those seen in NASH.It was concluded that future research should target the gut microbiome, hyperinflammation, and hepatobiliary congestion as integral components of potentially accelerated NASH development NAFLD‐comorbid patients following COVID‐19 recovery.