Laboratory Evaluation of Three Regimens of Treatment of Chronic Hepatitis B: Tenofovir, Entecavir and Combination of Lamivudine and Adefovir

Abstract

Background:Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination.Materials and Methods:Chronic hepatitis B patients with HBV-DNA more than 104 Copies/mL irrespective of their HBeAg status (n = 60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks.Results:After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters.Conclusion:Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.

Current Scenario of Hepatitis B and Its Treatment in India

“…Drug-resistant mutations reportedly develop in 7–16.4% (with 33% breakthrough). Combination of ADV + LAM 128 , 133 administered for 6–24 months was shown to result in rates of viral suppression of 42–53.3% and e seroconversion of 33–50%. Drug-resistant mutations occurred in only 7%, without any viral breakthrough.…”

“…ETV: 128 , 133 – 138 When administered for mean 6–36 months (maximum 5 years), ETV has resulted in viral suppression rates of 55–98%, and even higher rates were achieved with longer therapy duration (with e seroconversion in 18–56%). One study showed less response in genotype D, and another showed better response in e+ve cases; no drug resistance mutations were detected.…”

“…TDF: 128 , 133 , 137 – 140 When administered for 6–60 months, TDF resulted in viral suppression rates of 19–98%, which were higher with longer duration of therapy (with e seroconversion in 30–70%). One study showed less response in genotype D; no drug-resistant mutations were detected.…”

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients

“…Since LAM plus ADV combination therapy was recommended for CHB patients in 2011, 25 a meta-analysis conducted in China showed that LAM plus ADV combination therapy can enhance anti-HBV agents and reduce viral resistance, which could permit long-term use. 17 In addition, a clinical study conducted in India suggested that LAM plus ADV combination therapy was not inferior to ETV and TDF monotherapies, especially when treatment costs were taken into consideration, 40 although this strategy remains controversial. A global multicenter, randomized and double-blind study found that LAM plus ADV combination therapy could not significantly suppress HBV DNA levels and reduce viral resistance, 41 and thus some treatment guidelines do not recommend this strategy.…”

Efficacy of lamivudine combined with adefovir dipivoxil versus entecavir monotherapy in patients with hepatitis B-associated decompensated cirrhosis: A meta-analysis

“…Combination nucleoside‐nucleotide therapy which can decrease the risk of the development of drug resistance is also recommended for the treatment of cirrhotic patients, but not naïve patients . Studies have shown that chronic hepatitis B is more prevalent among low socio‐economic groups, and most individuals in these groups cannot afford treatment due to the high cost of drugs such as ETV and TDF . For this reason, LAM plus ADV combination therapy, while not recommended by most guidelines as first line agents, may be reasonable treatment in groups that cannot afford the first line agents.…”