Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver

Abstract

Anti-tumor necrosis factor (TNF)-α agents represent an effective treatment for chronic inflammatory diseases. However, some concerns about their potentially undesirable effects on liver function have been reported. On the other hand, evidence of their therapeutic effects on certain liver diseases is accumulating. Many data showed the safety of anti-TNF-α in patients with chronic hepatitis B and C and in liver transplanted patients even if a strict follow-up and prophylaxis are recommended in well-defined subgroups. On the other side, anti-TNF-α-induced liver injury is not a rare event. However, it is often reversible after anti-TNF-α withdrawal. Anti-TNF-α agents have been tested in advanced stages of severe alcoholic hepatitis and non-alcoholic fatty liver disease. Limited data on the efficacy of anti-TNF-α in patients with autoimmune hepatitis and primary biliary cholangitis are also available. In this review, we explored the hepatic safety concerns in patients receiving anti-TNF-α agents with and without pre-existent hepatic diseases. In addition, the available evidence on their potential benefits in the treatment of specific hepatic diseases is discussed.

Helicobacter pylori infection and nonalcoholic fatty liver disease: Time for large clinical trials evaluating eradication therapy

“…Moreover, in accordance with our previous systematic review supporting a positive association between H pylori ‐I and homeostasis model assessment IR (HOMA‐IR), as index of IR, the individuals with H pylori ‐I had higher glucose, insulin, and HOMA‐IR compared to those without previous or current H pylori ‐I. Noteworthy, the former had also higher liver function tests (alanine transaminase [ALT] and aspartate transaminase [AST]) and tumor necrosis factor (TNF)‐α ; TNF‐α is considered a key pathogenetic cytokine for NAFLD, and experimental data appear to confirm that anti‐TNF‐α agents may be significant for NASH treatment . Of note, one study published previous to ours reported that H pylori ‐I was one of the independent risk factors for the development of NAFLD; however, due to language restriction, this study cannot be presented in detail.…”

“…[ALT] and aspartate transaminase [AST]) and tumor necrosis factor (TNF)-α 15 ; TNF-α is considered a key pathogenetic cytokine for NAFLD, and experimental data appear to confirm that anti-TNF-α agents may be significant for NASH treatment. 17 Of note, one study published previous to ours reported that H pylori-I was one of the independent risk factors for the development of NAFLD 18 ; however, due to language restriction, this study cannot be presented in detail.…”

High prevalence of non‐alcoholic fatty liver disease among hidradenitis suppurativa patients independent of classic metabolic risk factors

“…24 Furthermore, adalimumab, an anti-TNFa drug, has demonstrated efficacy in the treatment of HS 1 and several experimental data suggest that TNF-a blockade might be an important target to treat NASH. 25 Comparing the diagnosis of NAFLD in patients with HS and controls, we found that those with HS had a higher prevalence of obesity and metabolic syndrome, and interestingly, greater liver stiffness. It should be noted that smoking was a confounding factor since active smokers are more frequent in the HS group.…”

“…This common pathogenesis may explain, at least in a subset of patients, the development of NASH in the absence of classic metabolic risk factors . Furthermore, adalimumab, an anti‐TNFα drug, has demonstrated efficacy in the treatment of HS and several experimental data suggest that TNF‐α blockade might be an important target to treat NASH …”

Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcoholic fatty liver disease: a retrospective cohort

“…Previous reports implied potential hepatotoxicity of anti-TNF-α agent, including idiosyncratic hepatic injury and autoimmune hepatitis. 36 In the rat models, previous experiments implied a pivot role of TNF-α in the pathogenesis of NASH. 11 Administration of infliximab could reverse diet-induced hepatic steatosis in rats.…”