Evolving Paradigms in the Treatment of Hepatitis B

Hepatitis B is a serious global health problem with over 2 billion people infected worldwide and 350 million suffering from chronic hepatitis B (CHB) infection. Infection can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) accounting for 320,000 deaths per year. Numerous treatments are available, but with a growing number of therapies each with considerable trade-offs, the optimal treatment strategy is not transparent. This dissertation investigates the relative efficacy of treatments for CHB and estimates the health related quality of life (HRQOL) and health utilities of mild to advanced CHB patients. A systematic review of published randomized controlled trials comparing surrogate outcomes for the first year of treatment was performed. Bayesian mixed treatment comparison meta-analysis was used to synthesize odds ratios, including 95% credible intervals and predicted probabilities of each outcome comparing all currently available treatments in HBeAg-positive and/or HBeAg-negative CHB patients. Among HBeAg-positive patients, tenofovir and entecavir were most effective, while in HBeAg-negative patients, tenofovir was the treatment of choice. Health state utilities and HRQOL for patients with CHB stratified by disease stage were elicited from patients attending tertiary care clinics at the University Health Network in Toronto. Respondents completed the standard gamble, EQ5D, Health Utilities Index Mark 3 (HUI3), Short-Form 36 version-2 and a demographics survey in their preferred language of English, Cantonese or Mandarin. Patient charts were accessed to determine disease stage and co-morbidities. The study included 433 patients of which: 294 had no cirrhosis, 79 had compensated cirrhosis, 7 had decompensated cirrhosis, 23 had HCC and 30 had received liver transplants. Mean standard gamble utilities were 0.89, 0.87, 0.82, 0.84 and 0.86 for the respective disease stages. HRQOL in CHB patients was only impaired at later stages of disease. Neither chronic infection nor antiviral treatment lowered HRQOL. Patients with CHB do not experience lower HRQOL as seen in patients with hepatitis C. The next step in this area of research is to incorporate the estimates synthesized by the current studies into a decision model evaluating the cost-effectiveness of treatment to provide guidance on the optimal therapy for patients with HBeAg-positive and HBeAg-negative CHB.Ph