Abstract
In chapter 2 and 3 hepatitis C virus (HCV) NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for resistance associated substitutions (RASs). RASs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. We found that prevalence
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of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. We found that Q80K is a highly stable and transmissible RAS and was present in a large part of Dutch HIV-coinfected men-who-have-sex-with men. The introduction and expansion of Q80K variants in this key population suggests a founder effect. Prevalence of N174 and S122 RASs was significantly higher in clade II than clade I viruses. In chapter 4 and 5 data were compared between HIV/hepatitis B virus (HBV) coinfected patients in the Dutch HIV Monitoring database and HBV mono-infected patients from two medical centers. We found that HIV/HBV coinfected patients no longer seem to be at increased risk for progression to end-stage liver disease (portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality) compared to HBV mono-infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity. Moreover, we found that HIV/HBV coinfected patients have a similar incidence of HBsAg seroconversion, but a decreased incidence of HBeAg seroconversion compared to their HBV mono-infected counterparts. Lastly, HBV mono-infected patients had a higher prevalence of advanced fibrosis at their first presentation compared to their HIV coinfected counterparts. In chapter 6 a systematic review was conducted to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV. We found that non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. In chapter 7 we investigated the effect of real-time medication monitoring on adherence to ribavirin in a randomized controlled trial during 24 weeks PEG-interferon/ribavirin±boceprevir or telaprevir. We found that adherence to ribavirin is high and that real-time medication monitoring did not influence this. In chapter 8 we assessed the association between ribavirin steady-state plasma levels and sustained virological response (SVR) in HCV infected patients treated with direct-acting antivirals (DAAs) plus RBV. 85% of these patients had one or more difficult-to-cure characteristics (i.e. treatment-experienced, HCV genotype 3, cirrhosis). We found that higher RBV steady-state plasma level was an independent predictor of SVR. In chapter 9 we provided 100 hepatitis B patients with a medication dispenser that monitored entecavir intake during 16 weeks therapy in a prospective study. We found that 70% of chronic hepatitis B patients exhibited good adherence to entecavir. Lastly, in chapter 10, data from all HBV-infected patients in a Dutch center were reviewed for outpatient loss to follow up. A total of 47% had ever been lost to follow-up. Main reasons for outpatient compliance and loss to follow-up were doctor’s advice and physicians presuming inactive disease respectively. In a questionnaire, the patients also affirmed to have relatively little insight into what the disease entailed. Thus, properly educating patients might increase understanding of the disease, help increase compliance, and improve treatment outcomes.
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