Disease Outcomes of Hepatitis Delta Genotype 5 vs Genotype 1

3D virus cells attacking a DNA strand
Patients with hepatitis delta virus (HDV) genotype 5 have demonstrated improved prognoses, better responses to pegylated interferon treatment.

Patients with hepatitis delta virus (HDV) genotype 5 have demonstrated improved prognoses, better responses to pegylated interferon (peg-IFN) treatment, and also had fewer episodes of hepatic decompensation, compared with patients with HDV genotype 1, according to study results published in the Journal of Hepatology.

Hepatitis B virus (HBV)/HDV coinfection commonly results in a rapid progression to hepatic decompensation and cirrhosis. This retrospective cohort study was designed to identify risk factors associated with HDV disease progression and to characterize treatment responses and clinical differences between HDV genotypes 1 and 5 in patients treated for HBV/HDV coinfection (hepatitis B surface antigen-positive [HBsAg+] and anti-HDV antibodies positive).

Researchers recruited individuals who were treated at the outpatient clinic in King’s College Hospital, London, between 2005 and 2016 who had follow-up data of >6 months; exclusion criteria for participation in the study included hepatitis C virus (HCV) and/or HIV coinfection or acute HDV infection. The final study cohort comprised 107 patients with genotype 5, of whom 100% were individuals of African origin and most had infection with HBV genotype E (93%); participants with genotype 1 were of predominantly European origins (56%) and infected with HBV genotype D (91%).

Among the 107 participants with anti–HDV immunoglobulin G (IgG), the mean age was 36.0 years (57% men) and they were followed for a median of 4.4 years (range, 0.6-28.1). Although baseline scores were statistically comparable, participants with actively replicating HDV experienced significantly more episodes of decompensation (P =.002), ascites (P =.005), and variceal bleeding (P =.032), and more often received liver transplantations (P =.043) compared with participants exposed to HDV, but uninfected.

Participants exposed to, but uninfected with, HDV had better event-free survival rates than participants with active HDV infection. The hazard ratio (HR) calculated for composite clinical events (decompensation, hepatocellular carcinoma, transplantation, and mortality) showed an HR for exposed-HDV vs active-HDV participants of 7.29 (95% CI, 2.43-21.87; P =.0024). HBV DNA levels were low and comparable between participants with HDV genotypes 1 and 5, with no differences observed in HDV RNA and HBsAg levels, or in albumin-bilirubin and fibrosis-4 scores.

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Participants with HDV genotype 5 showed more favorable disease progression compared with participants with HDV genotype 1. During follow-up, participants with HDV genotype 1 were more likely to experience hepatic decompensation (P =.002), ascites (P =.006), and liver transplant (P =.037).  The HR calculated for composite clinical events for genotype 5 compared with genotype 1 was 5.40 (95% CI, 1.65-17.70; P =.015).

A total of 42 participants were treated with peg-IFN, of whom 25 were eligible for analysis (median age 33.9 years; range, 17.8-52.3).  Of these 25 participants, 16 were HDV RNA negative at end of therapy, with 14 having a nonresponse, 11 maintaining HDV RNA status for more than 6 months, 5 relapsing within 6 months, and 1 relapsing after 22 months. Two participants had a viral breakthrough on therapy, and 7 were total nonresponders. Baseline characteristics of responders and nonresponders did not differ by age, sex, or presence of cirrhosis; however, differences were found in HBV genotype (P =.032) and baseline HDV RNA level (P =.002).

Although treatment duration was shorter for participants with genotype 5 (median duration was 48 weeks for both; mean duration was 38 weeks for genotype 5 vs 54 weeks for genotype 1; P =.007), 6-month post-treatment response rates were significantly better for those with HDV genotype 5 than those with genotype 1 (64% vs 10%; P =.013), and treatment response was associated with better clinical outcomes at follow-up (P =.043).

The investigators concluded that despite the limitations inherent to being a small, cross-sectional, single-center, retrospective study, the findings show “significant disease progression associated with hepatitis delta co-infection with HDV genotypic heterogeneity influencing clinical outcomes.” They also noted, “that genotype 5 patients, predominantly African in origin, have a more [favorable] disease outcome compared [with] HDV patients with genotype 1 and appear to have a better treatment response to peg-IFN. Identifying the risk factors for decompensation is important for patient education, clinical management and to delineate patients who need meticulous follow-up.”

Disclosure: This clinical trial was supported by Arbutus, Abbvie, Gilead, MSD, Shinoigi, and Vir. Please see the original reference for a full list of authors’ disclosures.


Spaan M, Carey I, Bruce M, et al. Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1 [published online January 22, 2020]. J Hepatol. doi: 10.1016/j.jhep.2019.12.028