Excessive PPI use accelerates liver disease progression in chronic HCV patients
Excessive and indiscriminate use of proton pump inhibitors (PPIs) may have perilous consequences for patients with chronic hepatitis C virus (HCV) infection, with a recent study showing that such pattern of exposure is associated with increased risks of progression of chronic liver disease to cirrhosis, hepatic decompensation and hepatocellular carcinoma.
The study included 11,526 HCV-infected veterans (mean age 53 years) who received HCV treatment, among whom 5,752 were PPI users. None of the patients had HIV coinfection, positive HBsAg and baseline gastro-oesophageal varices, among others. PPI use was measured using cumulative defined daily dose.
Multivariate Cox regression analysis found PPI exposure to be independently associated with an increased risk of developing cirrhosis (hazard ratio [HR], 1.32; 95 percent CI, 1.17 to 1.49). The cumulative probability of cirrhosis over 10 years of follow-up was significantly higher in patients who received PPI therapy (p<0.001), with the risk of cirrhosis increasing in a dose-dependent manner (p=0.003). The association was maintained through a sensitivity analysis that included only patients who achieved sustained virologic response and excluded those with alcohol abuse/dependence.
PPI use also increased the risks of hepatic decompensation by more than threefold (HR, 3.79; 2.58 to 5.57) and hepatocellular carcinoma by twofold (HR, 2.01; 1.50 to 2.70).
PPIs have been shown to substantially alter the composition of the gut microbiota in healthy individuals. Researchers postulated that the drugs may accelerate the progression of liver disease and promote the development of complications of cirrhosis by further exacerbating the dysbiosis associated with liver disease itself, leading to increased levels of pathogenic bacteria and bacterial translocation.
The present data underscore the importance of carefully assessing the use of PPIs in chronic HCV patients, researchers said. Additional studies with histological and clinical endpoints, as well as animal studies, are needed to elucidate the effect of long-term PPI use on the pathophysiological mechanisms of hepatic fibrosis.