entecavir and Chronic-Disease

The level of HBV-DNA is a crucial determinant of the progression to liver cirrhosis or hepatocellular carcinoma. Thus the effective suppression of HBV-DNA below the limit of detection of high sensitive assays is a major aim of treatment. This aim will be achieved in almost all patients with current available direct antiviral drugs. However, the development of drug resistance remains a main challenge for the future. Entecavir has a good profile regarding both antiviral efficacy and resistance profile in the treatment of previously untreated patients. After five year on Entecavir more than 90 % of HBe-Ag positive patients had achieved HBV-DNA below 300 copies/ml and resistance developed in only about 1 %. However, patients in whom there had been previous resistance to lamivudine have lower treatment responses and higher resistance rates because only one or two additional mutations in the HBV-polymerase gene are required for the development of entecavir resistance in contrast to three mutations required in treatment naïve patients. In summary, Entecavir adds a new milestone in the treatment of chronic hepatitis B.

Topics: Antigens, Viral; Antiviral Agents; Chronic Disease; Clinical Trials as Topic; Drug Resistance; Guanine; Hepatitis B; Hepatitis B virus; Humans; Liver Cirrhosis

Nucleic acid polymer (NAP) REP 2139 treatment was shown to block the release of viral surface antigen in duck HBV (DHBV)-infected ducks and in patients with chronic HBV or HBV/hepatitis D virus infection. In this preclinical study, a combination therapy consisting of REP 2139 with tenofovir disoproxil fumarate (TDF) and entecavir (ETV) was evaluated in vivo in the chronic DHBV infection model. DHBV-infected duck groups were treated as follows: normal saline (control); REP 2139 TDF; REP 2139 + TDF; and REP 2139 + TDF + ETV. After 4 weeks of treatment, all animals were followed for 8 weeks. Serum DHBsAg and anti-DHBsAg antibodies were monitored by enzyme-linked immunosorbent assay and viremia by qPCR. Total viral DNA and covalently closed circular DNA (cccDNA) were quantified in autopsy liver samples by qPCR. Intrahepatic DHBsAg was assessed at the end of follow-up by immunohistochemistry. On-treatment reduction of serum DHBsAg and viremia was more rapid when REP 2139 was combined with TDF or TDF and ETV, and, in contrast to TDF monotherapy, no viral rebound was observed after treatment cessation. Importantly, combination therapy resulted in a significant decrease in intrahepatic viral DNA (>3 log) and cccDNA (>2 log), which were tightly correlated with the clearance of DHBsAg in the liver.. Synergistic antiviral effects were observed when REP 2139 was combined with TDF or TDF + ETV leading to control of infection in blood and liver, associated with intrahepatic viral surface antigen elimination that persisted after treatment withdrawal. Our findings suggest the potential of developing such combination therapy for treatment of chronically infected patients in the absence of pegylated interferon. (Hepatology 2018;67:2127-2140).

Topics: Animals; Antiviral Agents; Chronic Disease; Drug Synergism; Drug Therapy, Combination; Ducks; Guanine; Hepadnaviridae Infections; Hepatitis B Virus, Duck; Hepatitis, Viral, Animal; Nucleic Acids; Polymers; Tenofovir

Topics: Antiviral Agents; Chronic Disease; Guanine; Hepatitis B; Humans; Male; Middle Aged; Retinal Diseases; Visual Acuity

A 58-year-old Arab-American male with HBeAg-negative chronic hepatitis B (HBV), presented with decompensated cirrhosis and a high HBV DNA level. He responded to entecavir with a significant reduction in serum HBV DNA level after 15 weeks of therapy with entecavir. However, he developed a progressive rise in prothrombin time/international normalized ratio (PT/INR) and bilirubin and underwent liver transplantation after receiving 22 weeks of entecavir therapy. Furthermore, with the continued use of combination entecavir and hepatitis B immunoglobulins (HBIG), he showed improvement in his clinical status with a nondetectable serum HBV DNA level 12 weeks after transplantation. He continued to maintain nondetectable serum HBV DNA 2 years following transplantation. To the best of our knowledge, this is the first reported case of a patient with decompensated chronic HBV who responded to entecavir both before and after transplantation without showing any evidence of recurrent HBV. Larger clinical trials are recommended to compare both short-term and long-term efficacy using entecavir among nucleoside-naïve decompensated chronic HBV patients before and after liver transplantation.

Topics: Antiviral Agents; Chronic Disease; DNA, Viral; Guanine; Hepatitis B; Hepatitis B virus; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged