Disease Loads and Status of Treatment

Background The hepatitis Delta virus (HDV) was first discovered by Rizzetto at the end of the 1970s while a cohort of patients with hepatitis B virus (HBV) presented in Italy with severe hepatitis. HDV is a defective, single-stranded RNA virus, which required life-cycle function provided by the HBV. Therefore HDV infection can only occur in patients with HBV infection, either as simultaneous coinfection or superinfection. As compared with chronic HBV mono-infection, HBV and HDV dual infections leads to more severe liver disease, with increased rates of cirrhosis and hepatic decompensation, and an increased incidence of hepatocellular carcinoma (HCC).

It has been estimated that about 5% of chronic HBV carriers are coinfected by HDV, leading to an estimated 15-20 million people are HDV carriers worldwide. However, its prevalence varies in different geographic regions. Certain areas or countries have been described as high prevalence, such as Central and West Africa, Eastern Europe, the Middle East, Mongolia, Russia, and Vietnam. Taiwan is a high endemic country of HBV infection before the implementation of the universal infant hepatitis B immunization program, which was launched in 1984. Thereafter, the prevalence rate of HBV infection decreased from 20% to 12% in the population with age more than 35 years. After 30-year of national HBV vaccination program, the prevalence of HDV infection in general population remains low, from 5-8% in 1986 to 4.4% in 2012. However, there was a significant decrease in the incidence of acute HDV superinfection in the general population, from 23.7% in 1983 to 4.2% in 1995. It is worth noting that the significant increased prevalence of HDV infection among injection drug users (IDUs), particular in those with human immune-deficiency virus (HIV) infection.

Currently treatment options of HDV infection remain limited, and interferon remains in standstill as the only available treatment. Relapse could still be observed after the treatment. Combination of nucleos(t)ide analogues (NAs) with IFN did not provide any benefit compared with IFN mono-therapy. Currently there are three novel therapeutic approaches for chronic HDV infection, namely Myrcludex B, lonafarnib, and REP2139-Ca. Of them, the REP 2139 in combination with PegIFN induced the clearance of serum HDV-RNA and of HBsAg in about half of the patients, followed by the raising of anti-HBs. If the preliminary data are confirmed, the combination of Peg IFN with REP 2139 will represent in the therapy of CHD in the near future. Therefore, an updated prevalence of HDV infection, especially in high endemic country of HBV infection, is needed to further understand the condition of CHD in Taiwan.

Patients and Methods I. Part 1 Prospective Study Investigators will organize a multicenter, prospective study platform to enroll all the HBV/HDV positive individuals from referral hepatology centers in Taiwan. A blood sample will be drawn at the time of the visit, after getting the approval of IRB. After centrifugation, the serum will be stored at -80°C, and sent for HDV RNA test. The PIs will review all HBsAg-positive individuals before the enrollment of this study. Demographics, clinical and laboratory data and the patient's history will be collected in a common database. Diagnosis of cirrhosis is based on the liver biopsy（Metavir F4 or Ishak ≧ 5）or liver ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices) or fibroscan >12kPa. The diagnosis of HCC is based on the criteria of practice guidelines of the European Association for the Study of the Liver (EASL) or the American Association for the Study of Liver Disease (AASLD). The fibroscan will be performed in patients with anti-HDV seropositivity.

Laboratory Test