Comparison of Telbivudine and Entecavir Therapy on Nephritic Function and Drug Resistance in Patients with Hepatitis B Virus-Related Compensated Cirrhosis

Abstract

Background: To compare the impact of telbivudine (LDT) and entecavir (ETV) administration on nephritic function. Method: One hundred thirty patients diagnosed with hepatitis B virus (HBV)-related compensated cirrhosis were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups. Results: The drug resistance rate was higher following LDT treatment compared to ETV treatment (16.9% vs. 1.5%, P=0.0006). The mean creatinine level decreased compared to baseline in the LDT group (0.81 vs. 0.94 mg/dl, P=0.000). The change in median glomerular filtration rate (eGFR) compared to baseline in the LTD and ETV groups was 22.3 and -3.3, respectively, at 2 years (P=0.000). In patients with mild nephritic injury (eGFR< 90 ml/min/1.73m²), the median eGFR increased by 28.0 ml/min/1.73m² in the LDT group and decreased by 4.3 ml/min/1.73m² in the ETV group (p=0.000). The eGFR in 88.5% of patients (23/26) from the LDT group increased > 90 ml/min/1.73m². The percentage of patients with an eGFR > 90 ml/min/1.73m² increased from 60.0% to 92.3% in the LDT group and from 64.6% to 69.2% in the ETV group. Conclusion: In patients with HBV-related compensated cirrhosis, LDT treatment was more effective in protecting nephritic function and was associated with a higher drug resistance rate, but did not contribute to a better outcome compared with ETV treatment.

A different inhibitor is required for overcoming entecavir resistance: a comparison of four rescue therapies in a retrospective study

“…We found that: ETV resistant mutants can be effectively inhibited with monotherapy of a different NA as long as the NA, like TDF selected in this study for the rescue therapy, is as potent as ETV; resistant mutants can also be inhibited by addition of a weak NA like ADV while keeping ETV in the regimens; a combination of ETV with TDF does not seem to result in significantly superior efficacy compared to TDF monotherapy though it doubles the expense; and a double dose of ETV largely fails to overcome the ETV drug mutant resistance. A fundamental mechanism for the emergence of NA drug resistance is the introduction of mutated nucleotide in the HBV pol gene coding the RT domain, which leads to changes in both amino acids and conformations of RT that the small molecule inhibitors can no longer bind and inhibit efficiently [4,13,14]. It is appreciable that TDF can potently inhibit the ETV drug resistant mutants because the inhibition of wildtype HBV replication by TDF is equivalent to ETV if not stronger, and they differ in chemical structure and target different pockets in the RT domain [15][16][17].…”

“…A fundamental mechanism for the emergence of NA drug resistance is the introduction of mutated nucleotide in the HBV pol gene coding the RT domain, which leads to changes in both amino acids and conformations of RT that the small molecule inhibitors can no longer bind and inhibit efficiently . It is appreciable that TDF can potently inhibit the ETV drug resistant mutants because the inhibition of wildtype HBV replication by TDF is equivalent to ETV if not stronger, and they differ in chemical structure and target different pockets in the RT domain .…”

Effect of entecavir in the treatment of patients with hepatitis B virus-related compensated and decompensated cirrhosis

“…Cirrhosis was diagnosed based on histological assessments of the liver, clinical symptoms, endoscopic examination, laboratory analysis, and sonographic results. Diagnoses of compensated and decompensated cirrhosis were made following liver disease management guidelines, including Child-Turcotte-Pugh score (14). Child-Turcotte-Pugh scores of 5 or 6, 7-9, or 10-15 were treated as Child-Pugh class A, B, or C, respectively.…”

“…The current therapy drugs include adefovir, tenofovir disoproxil fumarate, lamivudine (LAM), telbivudine and entecavir (11); however, LAM has been identified as having high drug resistance, and is no longer used as a first-line therapy for patients with CHB (12). Multiple clinical studies have proposed that entecavir may be used as a primary agent for patients with HBV-related liver cirrhosis irrespective of HBeAg serostatus (9,13,14). Entecavir is an antiviral agent that has been demonstrated to be an effective treatment of CHB (8).…”

Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis

“…CTP scores were mostly 5-6 and generally < 7, but as high as 9 in one study. Exclusion criteria were any decompensating events; HCV, HIV, or HDV infection; renal insufficiency; or excessive alcohol consumption [185][186][187][188][189][190][191].…”