Long‐Term Study of Hepatitis Delta Virus Infection at Secondary Care Centers: The Impact of Viremia on Liver‐Related Outcomes

Abstract

BaCKgRoUND aND aIMS: Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver-related outcomes is not really known outside the human immunodeficiency virus co-infection setting. We have therefore evaluated the long-term impact of HDV viremia on liver-related outcomes in a nationwide cohort of patients with hepatitis B and D co-infection, cared for at secondary care centers in Sweden. appRoaCH aND ReSUltS: In total, 337 patients with anti-HDV positivity, including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline, were retrospectively studied, with a mean follow-up of 6.5 years (range, 0.5-33.1). The long-term risks for liver-related events (i.e., hepatocellular carcinoma [HCC], hepatic decompensation, or liver-related death/transplantation) were assessed, using Cox regression analysis. The risk for liver-related events and HCC was 3.8-fold and 2.6-fold higher, respectively, in patients with HDV viremia compared with those without viremia, although the latter was not statistically significant. Among patients with HDV viremia with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver-related events was 81.9% and 64.0% after 5 and 10 years of follow-up, respectively. This corresponds to an incidence rate of 0.04 cases per person-year. CoNClUSIoNS: HDV RNA viremia is associated with a 3.8-fold higher risk for liver-related outcomes. The prognosis was rather poor for patients with HDV viremia without cirrhosis at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings may be of importance when making decisions about treatment and evaluating potential outcomes of upcoming antivirals against HDV. (Hepatology 2020;72:1177-1190). H epatitis delta virus (HDV) is considered to cause the most severe form of chronic viral hepatitis, with fast progression to liver cirrhosis and liver complications. (1,2) Previous studies evaluating the natural course of HDV infection have, however, been mainly from tertiary centers, with risk for referral bias toward patients with worse outcomes. (3-7) Published data on the rate of liver disease progression in patients with HDV viremia without cirrhosis are scarce, and knowledge of the outcomes in an unbiased population is lacking.

The changing context of hepatitis D

“…124 The clinical features of CHD in immigrants have been studied in 2 large series, one of 1,112 immigrants in France, 125 and the other of 337 immigrants in Sweden. 126 In the French series the mean age of patients was 36.5 years; 77% had active HDV infection, based on increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Sub-Saharan patients were younger, more frequently overweight and less often abused alcohol; their geographic origin was reflected by the diversity of HDV genotypes, with the scarcely characterised HDV-5 accounting for 32.7%, HDV-7 for 5.3%, HDV-6 for 3.2% and HDV-8 for 2.7% of infections in these patients.…”

Hepatitis D Virus and Hepatocellular Carcinoma

“…Although a correlation between the levels of HDV replication and the risk of liver complications has been documented [ 20 , 40 ], there is limited information on the levels of HDV and HBV replication in patients with HDV-associated HCC. Even more limited are the data on the levels of HDV replication within the tumor and in the surrounding nontumorous tissue.…”

AAV-HDV an Attractive Platform for the In Vivo Study of HDV Biology and Mechanism of Disease Pathogenesis

“…Approximately 5% of HBV carriers have been exposed to HDV, with a total of 15-20 million patients worldwide, although recent studies reported higher prevalence numbers [1][2][3]. HDV infection is associated with the most severe form of viral hepatitis with a twofold higher risk of developing cirrhosis, a threefold higher risk of developing hepatocellular carcinoma (HCC), and two fold increased mortality in comparison with HBV monoinfection [4][5][6]. Despite recent advances in the management of this condition, it still represents a significant medical burden [6][7][8].…”