From add-on cobination therapy to mono-therapy in treatment experienced CHB patients with viral resistance or partial responses: Results from an international mulicentre cohort study
Background and aim: Long-term viral suppression is a major goal to prevent disease progression in patients with chronic hepatitis (CHB). Aim of this ongoing cohort study is to investigate the safety and efficacy of mono-therapy with entecavir (ETV) or tenofovir (TDF) following a long-term rescue combination-therapy with ETV plus TDF in 23 CHB patients who were only partial responders or multidrug resistant.
Methods: Open label cohort study, investigator initiated, from 5 European centres. Patients were only included with suppressed viremia (LLoD < 69 IU/ml) for > 12 months during ETV plus TDF rescue combination treatment. ALT, HBV-DNA, qHBsAg were measured at baseline and every 3 months and resistance tests determined.
Results: 23 patients (15 HBeAg+), median age 48 years, 17 males, previously treated with a median of 5 lines of antiviral therapy (range 4 – 8), 8/22 (36%) with advanced liver disease, were included. Reason for switch from combination-therapy to mono-therapy was simplification in 22 cases and desire to have children in one case. Median ALT at baseline was 0.7 ULN (range 0.36 – 1.24). Median ETV plus TDF treatment duration was 31 months, median treatment duration of subsequent TDF mono-therapy (n = 20) was 26, for ETV (n = 3) 14 months, respectively. HBV-DNA remained suppressed during mono-therapy in 21 patients, in two patients there was a low level viremia detectable (maximum 265 IU/ml). One patient was on ETV with lamivudine experience, one cirrhotic patient on TDF, both with negative resistance testing. ALT levels remained stable in all patients, no hepatic flares occurred. The probability for a continuous HBV DNA suppression was not reduced in patients with adefovir or lamivudine resistance or in patients with advanced liver disease. One patient lost HBeAg 10 months on TDF mono-therapy, one cirrhotic patient developed an HCC. Quantitative HBsAg levels were not significantly different from end of combination therapy and end of observation during mono-therapy.
Conclusions: Mono-therapy with ETV or TDF after successful rescue combination therapy with ETV plus TDF in CHB patients harboring viral resistance patterns or showing only partial virologic responses to previous therapies was efficient, safe, and well tolerated in all patients subgroups.