Research Projects

Cirrhosis has been traditionally considered to be relentlessly progressive, ultimately culminating in clinical decompensations or hepatocellular carcinoma (HCC) with resultant increase in mortality. A perturbed gut-liver axis plays a key role in the pathogenesis and progression of compensated advanced chronic liver disease (cACLD). The effect of treatment of the etiology of liver disease on the gut-liver axis and the role of a persistently dysfunctional gut-liver axis on the progression of fibrosis and risk of clinical deterioration in cACLD despite adequate etiological control is underexplored. Chronic viral hepatitis could be a good example to look into. Because HCV infection can now be treated in the vast majority of patients, it's an ideal model for studying the impact of liver disease treatment on the microbiota. Furthermore, treating chronic viral hepatitis leads in an early resolution of liver inflammation and a delayed improvement in fibrosis, allowing to assess the impact of fibrosis on gut microbial diversity by evaluating the faecal microbiota at various time periods. With directly acting antivirals (DAAs), sustained virological response is attainable in most patients with chronic Hepatitis C virus (CHC). Nonetheless, despite viral eradication, a substantial proportion of patients still progress to clinical decompensations and the risk of HCC remains higher than in the general population. Thus, interrogation of the various components of the gut-liver axis (including gut microbiota, intestinal inflammation and permeability, and bile acid metabolomic profile) at different time points (before and after treatment with DAAs) will provide important insights into some of the important knowledge gaps. It will be a longitudinal follow up study, We aim to assess the differences in fecal microbiota, fecal short chain fatty acids, serum bile acid profile, intestinal inflammation and intestinal permeability in patients with HCV related cirrhosis with and without HCC, and also assess the effect of these facets of the gut-liver axis on the risk of developing clinical decompensations or HCC after attainment of SVR in patients with compensated cirrhosis without HCC at baseline. Apart from providing important insights into the many knowledge gaps in role of the gut-liver axis is cACLD, knowledge gathered from this study may also drive the development of novel prognostic and therapeutic tools based on the modulation of the gut-liver axis for the management of cACLD.