Safety of anti-TNF agents in patients with compensated cirrhosis: a case-control study

Abstract

Background: There is limited data on the use of anti-TNF agents in patients with concomitant cirrhosis. The aim of this study is to assess the safety of anti-TNF agents in patients with compensated cirrhosis who used these medications for the treatment of an underlying rheumatologic condition or IBD. Methods: Multicenter, retrospective, matched, case-control study. A one to three case-control match was performed. Adults who received anti-TNF therapy were matched to three adults with cirrhosis who did not receive anti-TNF therapy. Patients were matched for etiology of cirrhosis, MELD-Na and age. Primary outcome was the development of hepatic decompensation. Secondary outcomes included development of infectious complications, hepatocellular carcinoma (HCC), extra-hepatic malignancy, and mortality. Results: Eighty patients with cirrhosis who received anti-TNF agents were matched with 240 controls. Median age was 57.2 years. Median MELD-Na for the anti-TNF cohort was seven and median MELD-Na for the controls was eight. The most common etiology of cirrhosis was NAFLD. Anti-TNF therapy did not increase risk of decompensation (HR: 0.91, 95% CI: 0.64–1.30, p = 0.61) nor influence the time to development of a decompensating event. Anti-TNF therapy did not increase the risk of hepatic mortality or need for liver transplantation (HR: 1.18, 95% CI: 0.55–2.53, p = 0.67). Anti-TNF therapy was not associated with an increased risk of serious infection (HR: 1.21, 95% CI: 0.68–2.17, p = 0.52), HCC (OR: 0.45, 95% CI: 0.13–1.57, p = 0.21), or extra-hepatic malignancy (OR: 0.82, 95% CI: 0.29–2.30, p = 0.71). Conclusions: Anti-TNF agents in patients with compensated cirrhosis does not influence the risk of decompensation, serious infections, transplant free survival, or malignancy.

Therapeutic modulation of the liver immune microenvironment

“…There exist concerns regarding the use of anti-TNF agents in case of liver cirrhosis. In one study investigating 80 patients with compensated liver cirrhosis who received an anti-TNF agent for other reasons (240 matched controls studied), there was no evidence of increased decompensation, serious infections, malignancy, mortality, and transplant-free survival 163 . Most cases of cirrhosis in this study were because of NAFLD.…”

“…In one study investigating 80 patients with compensated liver cirrhosis who received an anti-TNF agent for other reasons (240 matched controls studied), there was no evidence of increased decompensation, serious infections, malignancy, mortality, and transplant-free survival. [163] Most cases of cirrhosis in this study were because of NAFLD. In a large US-based retrospective cohort including 226,555 patients with immune-mediated disorders, there was no beneficial effect of any anti-TNF agent regarding development of cirrhosis, NAFLD, or NASH in such patients [164,] raising doubts that TNF neutralization might be of relevance in the treatment of NAFLD despite interesting preclinical data.…”

Active Clinical Trials in Hepatic Encephalopathy: Something Old, Something New and Something Borrowed

“…If the positive outcomes are confirmed, it could also open new possibilities to treat HE or mHE patients with liver cirrhosis given that inflammation and immune response have been suggested to play a central role in the pathogenesis of HE, as demonstrated in patients and animal models [6,8,[64][65][66]. Unfortunately, although many nonsteroidal anti-inflammatory drugs, such as ibuprofen or celecoxib, or anti-TNF-α inhibitors, including infliximab or etanercept, which have revolutionized the treatment of multiple inflammatory conditions, including rheumatoid arthritis, psoriasis and inflammatory bowel disease, have shown promising results in animal models of liver disease [6,[67][68][69][70], they have also been associated with different degrees of hepatotoxicity when tested in patients, including the reactivation of viral hepatitis, drug-induced liver injury and de novo autoimmune hepatitis [71][72][73]. Therefore, the fact that only two drugs belonging to this category have reached testing in humans indicates that more efforts are needed to reduce the enormous gap between these and the other and more classical drugs, which still dominate the pharmacological field in HE.…”

Improvement in the mobility of a patient with fibroblast growth factor 23-related hypophosphatemic osteomalacia and decompensated liver cirrhosis in response to burosumab: a case report

“…Although the metabolism of antibody-based medication in patients with liver cirrhosis patients has not been described in detail, it has been reported that denosumab, a human monoclonal antibody that is used for the treatment of osteoporosis, can be safely used in patients with chronic liver disease, including liver cirrhosis [24]. In addition, a fully human monoclonal anti-tumor necrosis factor-α antibody that is used for the treatment of rheumatologic conditions was shown not to increase the risks of ascites, hepatic encephalopathy, or variceal bleeding in patients with compensated cirrhosis Endocrine Journal Advance Publication [25]. Although hepatic encephalopathy occurred twice in the present patient, it also occurred prior to burosumab treatment.…”