Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease reported in the United States. Some researchers have hypothesized that TNF-Î±, as a mediator of inflammation, might be a therapeutic target for NAFLD since inflammation seems to be a component of its etiology.
Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease reported in the United States. Some researchers have hypothesized that TNF-α, as a mediator of inflammation, might be a therapeutic target for NAFLD since inflammation seems to be a component of its etiology. However, case reports have identified a scattering of patients who have developed NAFLD during treatment with tumor necrosis factor inhibitors (TNFi). A study in the European Journal of Gastroenterology and Hepatology explores this paradox.
This study, a clinic case—control record review using records of veterans treat at VA hospitals located in Texas, identified The researchers examined 1 treatment and 3 control groups:
All patients were tested for the PNPLA3 gene, which has been associated with a predisposition to develop NASH.
Eight TNFi-treated patients developed some form of NAFLD. Five developed steatohepatitis and 3 were diagnosed with steatosis. These patients’ aminotransferase levels became elevated an average of 12 months after staring TNFi. Treating clinicians discontinued TNFi therapy in 5 patients, with \aminotransferase levels subsequently returning to normal in 2 to 8 months. None of these patients had evidence of autoimmune hepatitis or drug-induced liver injury.
TNFi-treated patients who developed NALFD had more methotrexate exposure than inflammatory controls. The researchers note that methotrexate’s hepatic effects can mimic NAFLD and might have contributed to ALT elevations.
Three-quarters of NAFLD patients had PNPLA3 genotype mutations compared to 38% of inflammatory controls, 88% of NASH controls, and 63% of healthy controls.
These researchers indicate that potential risk factors for ALT elevation during TNFi therapy include concurrent methotrexate use, Hispanic race, and PNPLA3 genotype mutations, and urge further study.