Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Abstract

Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B. NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease. However, drug resistance caused by their long-term use becomes a practical problem, which influences the long-term outcomes in patients. Liver transplantation is the only choice for patients with HBV-related end-stage liver disease. But, the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients. Recently, the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA. This may complicate the antiviral therapy and bring poorly prognostic outcomes. Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR, the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy. The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies. This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

Characterization of novel entecavir resistance mutations

“…Currently, 6 drugs are approved for the treatment of chronic hepatitis B including two formulations of interferon, (i.e. standard interferon α-2b (IFN-α-2b) and pegylated interferon α-2a (pegIFN-α-2a)), and 5 nucleos(t)ide analogues (NAs), lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine [1], and tenofovir for NA s -naïve and drug-resistant patients [1][2][3].…”

Accumulation of mutations in reverse transcriptase of hepatitis B virus is associated with liver disease severity in treatment-naïve Chinese patients with chronic hepatitis B

“…NAs are reverse transcriptase inhibitors which mimic the natural nucleosides and incorporate into the DNA chain so as to inhibit viral replication. 21 Treatment of NAs is known as an effective way to restrain HBV replication and restore liver function. However, nucleoside analog-resistant mutations, which always occur at the RT region, are the biggest obstacle during NAs treatment.…”

Identification of the transcriptional regulators by expression profiling infected with hepatitis B virus

“…Using aforementioned computational method, the procedure is repeated 1000,000 times for each N = (4, 5. . ., 20) and each threshold with assuming T = (0.5, 0.6. . ., 0.9).…”

“…However, these treatments are often considered as palliatives and limited by the serious side effects [16][17][18]. Therefore, novel better treatment approaches are imminently required to treating patients associated with chronic infection of HBV [19][20][21].…”