Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

Abstract

Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged treatment with nucleoside or nucleotide analogs (NUCs) for CHB. Materials and methods. Patients with CHB and advanced fibrosis or cirrhosis prior to treatment with NUCs for at least 1 year were offered inclusion in the study. We measured liver stiffness using transient elastography (TE) at follow-up. TE cut-off levels to Metavir classification for fibrosis stage F2, F3 and F4 were ≥7.2 kPa, ≥8.1, and ≥11.0 kPa, respectively. Results. Among 66 patients with a successful TE examination at follow-up, 53 patients (80%) had cirrhosis and 13 had (20%) advanced fibrosis (F3) prior to treatment. Median treatment duration was 50.5 months. Among patients with cirrhosis prior to treatment, 26 (49%) had liver stiffness below 11.0 kPa at follow-up, suggesting regression of cirrhosis. Among patients with advanced fibrosis (F3) prior to treatment, 10 (77%) had liver stiffness below 8.1 kPa after treatment, suggesting improvement of fibrosis. Conclusion. Transient elastography examinations demonstrate that prolonged treatment with NUCs in patients with CHB results in low liver stiffness, suggesting regression of fibrosis in a majority of patients with advanced fibrosis or cirrhosis.

Key Words::

• Cirrhosis
• hepatitis B
• nucleoside analogs
• transient elastography

Acknowledgements

We thank Kjell Block Hellum, Hans Kromann-Andersen, Peter Thielsen, Jan Gerstoft, Janne Jensen, Suzanne Lunding for help related to inclusion of patients, and statistician Steen Ladelund for important assistance with the statistical analyses. We are also grateful to the staff of the participating departments for recording data in DANHEP. This study was supported by the A.P. Moeller Foundation for the Advancement of Medical Science (grant support to Nina Weis) and by Anna and Preben Simonsens Foundation.

Declaration of interest: OW has been on the speaker's list for Roche A/S, MSD Pharmaceuticals, Gilead Sciences, Swedish Orphans A/S, Bristol-Myers Squibb and Novartis Healthcare A/S and has received research grants from Roche A/S, MSD Pharmaceuticals, Gilead Science, Bristol-Myers Squibb, Swedish Orphan A/S, and has furthermore been on advisory boards for Bristol-Myers Squibb, Tibotec Pharmaceuticals Ltd, Roche A/S, MSD Pharmaceuticals and Gilead Sciences. PL and BM have received unrestricted research grants from Roche A/S. PBC has received unrestricted research grants from Roche A/S and Schering-Plough A/S. NW has received an unrestricted research grant from Gilead Sciences and has been at the advisory board for Gilead Sciences. Roche A/S provided the Fibroscan device used in two of the clinics.