Evolution of hepatitis C virus genotype 1a vs. 1b distribution reflects profound changes of HCV epidemiology in Germany between 2004 and 2018 - Analysis of 17,093 patients from five consecutive registries including the German Hepatitis C-Registry (DHC-R)

Background and aims Hepatitis C virus (HCV) genotype (GT) 1 is the most common HCV GT in Western and Central Europe. Overall, GT1a is found more frequently in persons who have acquired HCV by drug use while HCV GT 1b has frequently been transmitted by transfusion of blood products before 1992. HCV GT 1 subtypes show different responses to some of the approved direct acting antivirals which still has relevance as, e.g. elbasvir/grazoprevir is widely used in some European countries. A more detailed knowledge on the evolution of HCV GT 1a vs. 1b would lead to a better understanding of HCV epidemiology which could have consequences for HCV elimination strategies.

Method The present analysis is based on five German non-interventional registry studies and comprises data on 17,093 HCV GT 1 patients documented between 2004 and 2018 [ML17071, ML19464, ML21645, ML25724 (initially sponsored by Roche Pharma AG) and the German Hepatitis C-Registry (DHC-R) initiated by the German Liver Foundation.

Results Overall, 7,662 patients were infected with HCV GT 1a and 9,431 patients with HCV GT 1b. GT 1a patients were younger (46.5 years vs. 51.2 years) and more often male (70% vs. 52%). Previous or ongoing drug abuse was documented more frequently for HCV GT 1a patients throughout the study periods with highest frequencies in the most recent period (2017-2018; 44% for HCV GT 1a and 10.3% for HCV GT 1b). Until 2013, more HCV GT 1b than HCV GT1a infected patients were obese and had diabetes mellitus while the proportion of patients with liver cirrhosis did not differ between these subgenotypes. A significant change in the HCV GT 1a/1b ratio was observed over time in men with less than 40% being infected with HCV GT 1a in 2004-2007 and about 60% in 2017/2018. In contrast, only 28-38% of women had HCV GT 1a infection throughout all study periods. There were no regional differences within Germany in HCV GT 1a/1b distribution despite a higher proportion of HCV GT 1b infected women in eastern Germany in 2004-2007 (86%).

Conclusion A marked increase of HCV GT 1a infection associated with drug use was observed in men but not women in Germany between 2004 and 2018. Metabolic comorbidities such as overweight and diabetes mellitus were associated with HCV GT 1b infected women.