Efficacy of telbivudine in the treatment of chronic hepatitis b and liver cirrhosis and its effect on immunological responses

Abstract

This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.

Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies

“…It was also significantly higher in patients with advanced fibrosis, while tenascin, type IV collagen and TIMP-1 did not reach a significant difference [ 34 ]. Telbivudine, used in the treatment of CHB, lowered HA levels in patients with cirrhosis [ 35 ].…”

Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity

“…15,46,47 Thus, for this clinical scenario, there is an unmet need to develop new immunomodulatory or antiviral therapy strategies that do not carry the risk of viral stimulation due to global immune suppression as it is known for cortisone. The antiviral and anti-inflammatory properties of telbivudine [24][25][26][27] inspired us to evaluate its potential to treat B19V-associated inflammatory cardiomyopathy. Given the vasculotrope nature of B19V 2,3 and the evidence that B19V modulates inflammatory signalling and apoptosis in endothelial cells, 20 we evaluated at first potential endothelial-protective effects of telbivudine in B19V-infected endothelial cells.…”

Viral myocarditis

“…Telbivudine is an antiviral nucleoside analogue reverse transcriptase inhibitor, which is especially effective for retroviral and pararetroviral (hepatitis B viruses) infections and has pleiotropic immunomodulatory/anti-inflammatory properties [ 86 – 89 ]. The single-stranded B19V DNA genome replicates through a specific rolling-hairpin-mechanism to generate a double-stranded DNA molecule mimicking DNA-synthesis during the reverse transcription process comparable with retroviruses and hepatitis B viruses [ 90 ].…”

“…1 ). This specific antiviral working mechanism of telbivudine together with its anti-inflammatory effects [ 86 – 89 ] have been the rationale to evaluate the efficacy of telbivudine in myocarditis associated with B19V transcriptional activity: the PreTopic Study (EudraCT-Number: 2016-004825-17).…”