Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective?

Benefit of transaminase elevations in establishing functional cure of HBV infection during nap‐based combination therapy

“…In the absence of hepatic decompensation and viral rebound, transaminase flares are considered to be immune‐mediated and may reflect clearance of infected hepatocytes from the liver via T‐cell mediated cytolytic mechanisms 12,13 . This is consistent with the well‐established correlation of transaminase flares in HBV mono‐infection with reduction of viraemia and or HBeAg seroconversion in the absence of treatment 2 or during NUC therapy 7,8 or with HBsAg loss 14 and the establishment of partial cure (HBV DNA ≤2000 IU/mL, normal ALT) or functional cure of HBV (HBV DNA TND, HBsAg <LLOQ, normal ALT) during interferon therapy 3,6,9 …”

“…During the natural history or treatment of chronic HBV infection, transient elevations in transaminases (flares) are observed in a minority of subjects, even those with advanced cirrhosis, and are rarely associated with hepatic decompensation, except during acute infection or when HBV DNA titres exceed 10 9 copies/mL. [2][3][4][5][6][7][8][9][10][11] In the absence of hepatic decompensation and viral rebound, transaminase flares are considered to be immune-mediated and may reflect clearance of infected hepatocytes from the liver via T-cell mediated cytolytic mechanisms. 12,13 This is consistent with the well-established correlation of transaminase flares in HBV mono-infection with reduction of viraemia and or HBeAg seroconversion in the absence of treatment 2 or during NUC therapy 7,8 or with HBsAg loss 14 and the establishment of partial cure (HBV DNA ≤2000 IU/mL, normal ALT) or functional cure of HBV (HBV DNA TND, HBsAg <LLOQ, normal ALT) during interferon therapy.…”

“…12,13 This is consistent with the well-established correlation of transaminase flares in HBV mono-infection with reduction of viraemia and or HBeAg seroconversion in the absence of treatment 2 or during NUC therapy 7,8 or with HBsAg loss 14 and the establishment of partial cure (HBV DNA ≤2000 IU/mL, normal ALT) or functional cure of HBV (HBV DNA TND, HBsAg <LLOQ, normal ALT) during interferon therapy. 3,6,9 Nucleic acid polymers (NAPs) selectively block the assembly / secretion of HBV subviral particles (SVP) 15,16 from hepatocytes harbouring cccDNA or integrated HBV DNA, 17 allowing clearance of serum HBsAg by host mediated processes. This effect is accompanied by declines in intracellular HBsAg in vitro 15,18 and clearance of intrahepatic HBsAg in vivo and in humans.…”

“…At least 292 million people worldwide are chronically infected with HBV, 1 and this hepatotropic infection is associated with fibrosis, cirrhosis and hepatocellular carcinoma. During the natural history or treatment of chronic HBV infection, transient elevations in transaminases (flares) are observed in a minority of subjects, even those with advanced cirrhosis, and are rarely associated with hepatic decompensation, except during acute infection or when HBV DNA titres exceed 10 9 copies/mL 2‐11 . In the absence of hepatic decompensation and viral rebound, transaminase flares are considered to be immune‐mediated and may reflect clearance of infected hepatocytes from the liver via T‐cell mediated cytolytic mechanisms 12,13 .…”

Association of signal transducer and activator of transcription, interleukin-6, and interleukin-10 positivity with antiviral treatment in cirrhotic liver samples from patients with the hepatitis B or C virus

“…The main causes of liver cirrhosis are HBV, HCV, alcohol use, nonalcoholic steatohepatitis, and hereditary metabolic defects 7 . In Turkey and the rest of the world, HBV and HCV are the main cause of terminal-stage liver diseases 8 . It is estimated that over 350 million people worldwide are chronically infected with HBV and that about 600 thousand people die annually from HBV 8 .…”