November 10, 2010

AASLD: Cure Rates for HDV Depend on Genotype and Baseline Viral Load

Bob Roehr

November 10, 2010 (Boston, Massachusetts) — An estimated 20 million people worldwide are infected with hepatitis D virus (HDV), primarily in the Mediterranean region, sub-Saharan Africa, the Middle East, and the northern part of South America. Nearly a dozen studies on the topic were reported here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, many of which show a virologic response rate of around 50% with interferon. Response to treatment depends on genotype and baseline viral load.

Sarah Hughes, MD, from the Institute of Liver Studies, King's College Hospital, London, United Kingdom, reported some of the better sustained viral response rates (SVR) with pegylated-interferon alfa-2a — 54% for patients with HDV and hepatitis B virus (HBV) coinfection.

Infection with HDV is often simultaneous with HBV infection, or happens subsequently through superinfection, Dr. Hughes told Medscape Medical News. HDV "hijacks the surface-antigen coat from [HBV], which is the only thing it requires from [HBV]. Without that, the delta capsule cannot be assembled and released. So it absolutely has to have the contemporary presence of [HBV] in order to propagate," she explained. HDV causes rapid liver decompensation with cirrhosis and an increase in mortality, she added.

Dr. Hughes said there were 4 published studies on treating HDV with pegylated-interferon alfa-2a prior to her team's investigation, "but they were all very small. I think the largest had 90 patients. The highest [SVR] rate was 43%, but the average was about 25%."

In her retrospective study (n = 17), 64% of the participants cleared HDV RNA by end of treatment with pegylated-interferon alfa-2a. After 24 weeks of follow-up, 54% achieved SVR.

Baseline HDV RNA level was a significant predictor of response to therapy in the study by Dr. Hughes and colleagues. Those who achieved a SVR had a baseline HDV RNA level of 1.3 × 104 copies/mL; nonresponders had a baseline HDV RNA level of 2.1 × 106 copies/mL (P = .003). HDV RNA levels higher than 1.96 × 105 copies/mL predicted treatment failure (P = .001; 100% positive predictive value and 100% sensitivity).

"All of our patients were treatment-naive, which may in part explain why our response rate was higher," she said.

Unlike the other studies in which patients predominately were HDV genotype 1 or unreported, "we have a spread of genotypes. What we found is that 100% of those who are genotypes 5/6 responded to interferon. That was despite the fact that 2 patients had truncated courses of treatment."

Viral load is associated with the ability to clear HDV on therapy, and the viral loads of genotypes 5/6 are much lower than those of genotype 1, which might in part explain their higher rate of viral clearance.

"Every genotype of [HDV] has a very specific geographic distribution. In London, where there is a very diverse immigrant population, . . . it is worth genotyping. If you live in Germany or Eastern Europe, then all of the patients will be genotype 1," she said.

"[Alanine aminotransferase levels] at baseline didn't make a difference in response, and the presence or absence of cirrhosis didn't seem to make any difference either," Dr. Hughes noted.

Dr. Hughes believes that the most likely use of this new information will be in attempting to see whether shorter courses of therapy — 24 rather than 48 weeks — are possible with the more easily cleared genotypes.

"If you don't look for [HDV], you are not going to find it. We routinely test all of our HBV antigen-positive patients for seroreactivity to [HDV]; we routinely do [HDV immunoglobulin G] on all of our patients." The patients often are coinfected with [hepatitis C virus] because of transmission through shared injection drug equipment, she said.

The HDV actually suppresses HBV replication to very low levels: "9 in 10 patients have no detectible [HBV] replication at all. I'm not saying you can ignore the B, but you have to treat the [HDV]. There are a subset of patients who are e-antigen positive, which is quite unusual, who do have slightly higher levels of HBV replication. In those patients, it probably is reasonable to treat B alongside D. It is absolutely not evidence-based, but theoretical," the British investigator said.

Sometimes with successful treatment of HDV, you "unmask some HBV replication, and at that stage, you probably treat those patients as if they were B-monoinfected," she added.

Support for the analysis came from the UK National Health Service and academic sources. Dr. Hughes has disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 455. Presented October 30, 2010.

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