Hepatitis B virus YMDD-motif mutations with emergence of lamivudine-resistant mutants: a threat to recovery

Hepatitis B virus (HBV) is a crucial public health problem with approximately 350 million affected people and a death rate of 0.5 to 1.2 million per year worldwide. It proceeds to end-stage liver diseases including cirrhosis with hepatic decompensation and hepatocellular carcinoma (HCC). Pakistan lies in the endemic region with 3% HBV carrier rate in the country. The differences in disease outcome and antiviral treatment response among HBV infected patients are variable in different regions of the world due to marked differences in HBV genotypes. These variants are different in their serological reactivity patterns, virus replication, liver disease severity and antiviral treatment responsiveness. The highly mutating nature of HBV is the major cause of its ever increasing antiviral resistance. Importantly the tyrosine-methionine-aspartate-aspartate (YMDD)-motif mutants emerge during prolonged lamivudine treatments that elicit immune clearance. This review deals with the HBV nature, mutation appearance and particularly emphasizes on lamivudine induced mutations in a conserved region (YMDD motif) which is further worsening the antiviral therapies with passage of time.