Physiopathology and treatment of viral hepatitis
The specificity of our group is the strong interaction between a large clinical center and a laboratory to address major questions regarding patients with chronic viral hepatitis B and C. Chronic hepatitis B and C represent a major public health burden (600,000 patients in France with a strong morbidity and mortality (5000 deaths per year)). Our clinical center follows large cohorts of patients untreated (natural history) or treated (long term impact of treatment). For these patients, followed for years, a complete clinical and biochemical data-base is available with a biotheque (serum and liver tissue samples). We develop multiple collaborations with academic laboratories and the industry. . In the future we will continue to develop a strong activity in clinical trials and we will multiply our translational research projects to better understand the physiopathology and the response to new therapies. Current research (using genomic, transcriptome, miRNAs expression…) will be continued to maintain a strong translational research.
It is mandatory to determine the fibrosis stage during chronic viral hepatitis C and B. It reflects the progression of the disease and the need for treatment. Invasive and non-invasive methods are available to stage fibrosis. With non-invasive methods it remains difficult to discriminate early stages of fibrosis with high accuracy. Liver biopsy is invasive and sometimes difficult to standardize, therefore to avoid invasive exams and to increase the efficacy of non-invasive methods to score fibrosis. In the lab, we are interested in the analysis of differential genes expression at the different fibrosis stages and during fibrosis progression. We focus on the expression of genes and miRNAs involved in the different mechanisms of fibrogenesis. MiRNAs are particularly interesting as biomarkers because they are very stable as compared to mRNAs and they can be detected in parrafin-embed liver and serum samples.
Among our different research projects, we are studying biomarkers to help to predict fibrosis progression and response to the treatment. We have compared the expression of different genes and miRNAs in patients at different stages of fibrosis and in patients either responders or non-responders to the treatment. We established a list a genes which expression is associated with different stages of fibrosis and with the response to the treatment.
Genome wide association studies identified a strong association between IFNL3 polymorphisms and response to pegylated-interferon plus ribavirin in patients with chronic hepatitis C, especially those infected with HCV genotype 1. In our lab, we demonstrated that in patients infected with HCV genotype 4, these polymorphisms were, as well, strongly associated with the response to pegylated-interferon plus ribavirin. Moreover, our results demonstrated that the expression of mir-122 which controls HCV replication is highly associated with IFNL3 polymorphims. Our results suggested that molecular mechanisms behind IFNL3 polymorphisms may regulate mir-122 expression.
Interestingly, in patients with chronic hepatitis B, IFNL3 polymorphisms where not associated with the response to interferon based therapies. In the field of hepatitis B, our research showed the benefit of the assessment of HBs Ag during the follow up of patients with chronic hepatitis B. The expression of HBs Ag in the serum, during the course of therapy, is associated which the response. Moreover, the level of HBs Ag level is associated with the fibrosis stage.
Pr Asselah and Pr Marcellin are involved in different clinical trial as principal investigators. These trials test the new combination of antivirals. The results have been published in high quality international journals.
Pr Marcellin organizes a conference in Paris, the Paris Hepatitis Conference (www.aphc.info), every year, for already 10 years. This conference aims to present the different breakthroughs in the field of viral hepatitis and the different aspects of the support of patients especially in the era of new drugs combination. During the last conference we have gathered up to 1300 hepatologists from 70 different countries.