ABSTRACT
BACKGROUND & AIMS: HBV reactivation after liver transplantation may be related to persistence of covalently closed circular (ccc) DNA. We investigated the safety of HBV prophylaxis withdrawal in selected HBV transplanted patients. METHODS: Thirty patients transplanted 64-195months earlier (23 males, median age 56yrs), HBsAg-positive, HBeAg, and HBV-DNA negative at transplant (43% HCV/HDV co-infected), with undetectable intrahepatic total and ccc-DNA were enrolled. All patients underwent HBIg withdrawal and continued lamivudine with monthly HBsAg and HBV-DNA monitoring and sequential liver biopsies. Those with confirmed intrahepatic total and ccc-DNA undetectability 24weeks after stopping HBIg, also underwent lamivudine withdrawal and were followed-up without prophylaxis. RESULTS: Twenty-five patients did not exhibit signs of HBV recurrence after prophylaxis withdrawal (median follow-up 28.7months, range 22-42). Five patients became HBsAg-positive: one early after HBIg withdrawal, the other four after HBIG and lamivudine withdrawal. None of these patients experienced clinically relevant events. In the first patient, HBIg were reinstituted with prompt HBsAg negativization. Of the other four, one remained HBsAg-positive with detectable HBV-DNA and mild ALT elevation and was successfully treated with tenofovir. In the remaining three, HBsAg positivity was transient and followed by anti-HBs seroconversion, thus no antiviral treatment was needed. CONCLUSIONS: Patients with undetectable HBV viremia at transplant and no evidence of intrahepatic total and cccDNA may safely undergo cautious weaning of prophylaxis, showing low rate of HBV recurrence after a 2 year follow-up. Undetectability of intrahepatic ccc-DNA may help to identify patients at low-risk of recurrence, yet studies with longer follow-up are needed.
Subject(s)
Antibiotic Prophylaxis , Antiviral Agents/administration & dosage , Hepacivirus , Hepatitis B Antibodies/administration & dosage , Hepatitis B, Chronic/prevention & control , Liver Cirrhosis/surgery , Liver Transplantation , Adult , Aged , Antiviral Agents/therapeutic use , DNA, Circular/analysis , DNA, Circular/blood , DNA, Viral/analysis , DNA, Viral/blood , Female , Follow-Up Studies , Hepatitis B Antibodies/therapeutic use , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use , Lamivudine/administration & dosage , Lamivudine/therapeutic use , Liver/chemistry , Liver/virology , Liver Cirrhosis/virology , Male , Middle Aged , Secondary PreventionABSTRACT
BACKGROUND: Life-long prophylaxis against HBV recurrence is recommended in patients transplanted for HBV-related disease. The risk of HBV reactivation is due to persistence of covalently closed circular (ccc) DNA in hepatocytes. Whether cccDNA persists in livers of long-term transplant survivors who received conventional prophylaxis is unknown. AIM: To investigate the presence of intrahepatic total and cccDNA in transplanted patients with no evidence of biochemical markers of HBV recurrence. METHODS: Intrahepatic total and cccDNA were assessed using sensitive nested and real-time PCR from 44 HBsAg-positive patients (75% male; mean age 55.2+/-8.9 years) who had undetectable serum HBV-DNA at transplant. The mean follow-up after transplant was 88.3 months (range, 18-159). RESULTS: One patient underwent HBV recurrence after transplant and was the only who tested positive for both intrahepatic total HBV-DNA and cccDNA. Of the 43 patients negative for all serological markers of HBV infection, only 2 tested positive for intrahepatic total HBV-DNA, but none for cccDNA. CONCLUSIONS: Most patients with undetectable HBV-DNA at transplant, who received conventional HBV prophylaxis, have no evidence of intrahepatic total HBV-DNA and cccDNA. cccDNA should be considered a new additional diagnostic tool, also to identify patients at low risk of HBV recurrence after liver transplantation.
Subject(s)
DNA, Circular/analysis , DNA, Viral/analysis , Hepatitis B, Chronic , Liver Transplantation , Secondary Prevention , Adult , Aged , Antiviral Agents/therapeutic use , Female , Hepatitis B virus/drug effects , Hepatitis B virus/physiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/therapy , Hepatocytes/metabolism , Hepatocytes/pathology , Hepatocytes/virology , Humans , Immunosuppression Therapy , Liver/pathology , Liver/physiology , Liver/virology , Liver Cirrhosis/etiology , Liver Cirrhosis/therapy , Liver Transplantation/immunology , Liver Transplantation/pathology , Male , Middle Aged , Survivors , VaccinationABSTRACT
Highly pathogenic H5N1 virus can infect a variety of animals and continually poses a threat to animal and human health. Here, phylogenetic analysis of the hemagglutinin and neuraminidase genes indicated that the hemagglutinin gene of all human isolates, although very similar to each other, fell within different clades corresponding to antigenically distinguishable variants. Likewise, the N1 neuraminidase gene forms a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. So, although all H5N1 viruses were derived from ancestors circulating in south-east Asia more than ten years ago, since 2003 they have evolved into geographically distinct groups within each country.
