One‐quarter of chronic hepatitis D patients reach HDV‐RNA decline or undetectability during the natural course of the disease

Abstract

Background: Spontaneous HDV-RNA fluctuations, assessed by nonstandardised inhouse assays, have been reported during the course of chronic hepatitis delta (CHD).Aims: To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers.Methods: A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined.Results: Most participants were male, middle-aged, white European, and HBeAgnegative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median-HDV-RNA was 5.3 (4.2-6.5) log 10 IU/mL, HBsAg 4.0 (3.5-4.3) log 10 IU/mL, and HBV-DNA 1.6 (1.0-2.6) log 10 IU/mL; ALT values were normal in 13 (23%). During a mean follow-up of 5.6 (3-16) years, 14 (25%) showed ≥2log 10 HDV-RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV-RNA. Four patients (7%) lost HBsAg, with undetectable HDV-RNA. The remaining 42 (75%) had persistently detectable HDV-RNA. During follow-up, patients with a ≥2log 10 HDV-RNA decline showed a greater HBsAg drop (−0.7 ± 1.1 vs −0.09 ± 0.9 log IU/mL; P = 0.039) than those with a <2 log 10 HDV-RNA decline. Overall, ALT and HBV-DNA levels decreased over time. There were no differences in clinical outcomes between groups.Conclusions: One-quarter of untreated CHD patients showed a ≥2log 10 decline in HDV-RNA and 20% reached HDV-RNA undetectability during a mean follow-up of | 463 PALOM et AL. How to cite this article: Palom A, Sopena S, Riveiro-Barciela M, et al. One-quarter of chronic hepatitis D patients reach HDV-RNA decline or undetectability during the natural course of the disease.

Editorial: natural history of hepatitis delta virus‐induced liver disease ‐ less severe today but still needs attention

“…[2][3][4] Support for a milder CHD course is described recently in Alimentary Pharmacology and Therapeutics. In that study, Palom et al 5 report a retrospective multicentre study on a CHD cohort of 56 patients with compensated liver disease followed longitudinally for a mean duration of 5.6 (3-16) years. Two-thirds were on nucleos(t)ide analogue (NA) treatment.…”

Standardized Hepatitis B Virus RNA Quantification in Untreated and Treated Chronic Patients: a Promising Marker of Infection Follow-Up

“…However, this study mainly aimed to analyze the HBV RNA trend over time and its association with HBV DNA. To facilitate this purpose, we converted DNA test results from IU/mL to copies/mL using the conversion factor of 5.82 ( 38 ).…”

Review article: emerging insights into the immunopathology, clinical and therapeutic aspects of hepatitis delta virus

“…64 Spontaneous fluctuation of both HBV and HDV viral markers has also been observed, and a recent retrospective study of untreated HDV patients showed that one-quarter of them achieved a spontaneous HDV RNA decline associated with HBsAg and HBV DNA decreases. 71 Clinical details of HDV infection are summarised in Table 1 and Figure 4.…”