Intrahepatic Hepatitis B Virus Covalently Closed Circular DNA Can Be a Predictor of Sustained Response to Therapy

Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

“…Recent studies have shown that suppression of HBV-DNA in serum does not indicate clearance of the virus in hepatocytes, 18,27 and the long half-life of cccDNA in infected hepatocytes is responsible for viral reactivation fol- lowing drug cessation. 4,28 During antiviral therapy with ADV monotherapy, cccDNA could be reduced by nearly 1 log 10 and intracellular total HBV DNA by 1.6 log 10 .…”

“…Detection and quantification of cccDNA from liver biopsies were recently demonstrated using a selective real-time polymerase chain reaction (PCR) assay. 8,18 Those studies found that cccDNA level strongly correlated with total intracellular HBV DNA level and that, in general, intrahepatic HBV-DNA levels were substantially lower after HBeAg seroconversion in patients receiving oral ADV for 1 year. 8 Interestingly, a significant, 0.8 log decrease in cccDNA copies per cell was demonstrated after nucleotide analogue therapy.…”

“…However, histological analysis of liver biopsies suggested that changes in cccDNA occurred mainly by noncytolytic mechanisms because the number of HBV antigen-positive cells remained unchanged at the end of treatment. 8 In a recent study by Sung et al, 18 it was shown that intrahepatic cccDNA and total HBV-DNA levels were superior to serum HBV-DNA as predictors of sustained virological response to antiviral therapy in patients who received either lamivudine monotherapy or combination therapy of lamivudine and pegylated interferon alpha-2b (peg-IFN) for 1 year. Because liver biopsies were taken only at the end of therapy, the impact of combination therapy on intracellular viral DNA reduction could not be investigated.…”

Response predictors to treatment with pegylated interferon in chronic hepatitis B

“…59,67 In 26 HBeAg-positive patients that completed the combined treatment of PEG-IFN alpha-2b for 32 weeks and lamivudine for two years, a level of HBsAg < 1,500 UI/ mL presents 71% sensitivity and 84% specificity to predict SVR. 51 In an international study with PEG-IFN alpha-2a, in HBeAg patients, a level < 10 UI/mL in week 48 and decline during the treatment > 1 log UI/mL can predict a sustained disappearance of HBsAg three years after the use of PEG-IFN alpha-2a, with or without the concomitant use of lamivudine.…”

Controversies Regarding the Hepatitis B Immune Globulin Prophylaxis (HBIG) for Liver Transplantation Recipients

“…Neff et al [13] found that none of the 51 patients with undetectable HBV DNA pre-LT experienced evidence of HBV viral recurrence post-LT regardless of the different prophylactic strategy [30,50] . However, following studies showed that suppression of HBV-DNA in serum does not indicate clearance of the virus from hepatocytes [46,66] and the long half-life of cccDNA in reinfected hepatocytes is responsible for viral recurrence following OLT [67][68][69][70][71] . Therefore, the authors suggested the complete withdrawal of prophylaxis with caution.…”