Use of serum biomarkers in staging of canine hepatic fibrosis.

Accurate staging of hepatic fibrosis (HF) is important for treatment and prognosis of canine chronic hepatitis. HF scores are used in human medicine to indirectly stage and monitor HF, decreasing the need for liver biopsy. We developed a canine HF score to screen for moderate or greater HF.

Mutations in TP53 and CTNNB1 in Relation to Hepatitis B and C Infections in Hepatocellular Carcinomas from Thailand.

Hepatocellular carcinoma (HCC) may develop according to two major pathways, one involving HBV infection and TP53 mutation and the other characterized by HCV infection and CTNNB1 mutation. We have investigated HBV/HCV infections and TP53/CTNNB1 mutations in 26 HCC patients from Thailand. HBV DNA (genotype B or C) was detected in 19 (73%) of the cases, including 5 occult infections and 3 coinfections with HCV.

Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C.

Unlabelled: Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC.

The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: a case control study.

Background & Aims: Nodular regenerative hyperplasia (NRH) leading to non-cirrhotic portal hypertension has been described in HIV-infected patients and has been linked to didanosine. The relation between NRH and other antiretrovirals remains unclear.

Methods: A case-control study was performed in 13 patients with NRH and 78 controls matched for time of inclusion, baseline CD4, and duration of follow-up.

Pharmacological inhibition of Frizzled-7 displays anti-tumor properties in hepatocellular carcinoma.

Background & Aims: We previously reported the frequent overexpression of the FZD7 membrane receptor in hepatocellular carcinoma (HCC) and its role for controlling cancer phenotype. Herein, this study aimed at assessing the anticancer properties of compounds inhibiting FZD7 activity by disrupting its binding with the cytosolic Dishevelled (DVL) adaptator.

Methods: We have designed small interfering peptides (RHPDs) that are able to enter within cells and to competitively antagonize the binding of FZD7 to the PDZ domain of DVL.

Non-invasive assessment of liver fibrosis progression in hepatitis C patients retreated for 96 weeks with antiviral therapy: a randomized study.

Background: The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores.

Aim: The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis.

Method: Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks.

Early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected cynomolgus monkeys.

Lassa virus causes a hemorrhagic fever endemic in West Africa. The pathogenesis and the immune responses associated with the disease are poorly understood, and no vaccine is available. We followed virological, pathological, and immunological markers associated with fatal and nonfatal Lassa virus infection of cynomolgus monkeys.

DNA vaccination in combination or not with lamivudine treatment breaks humoral immune tolerance and enhances cccDNA clearance in the duck model of chronic hepatitis B virus infection.

This study used a duck hepatitis B virus (DHBV) model to evaluate whether a novel DNA vaccination protocol alone or associated with antiviral (lamivudine) treatment was able to clear the intrahepatic covalently closed, circular viral DNA (cccDNA) pool responsible for persistence of infection. DHBV carriers received DNA vaccine (on weeks 6, 10, 13, 14, 28 and 35) targeting the large envelope and/or core proteins alone or combined with lamivudine treatment (on weeks 1-8) or lamivudine monotherapy. After 10 months of follow-up, a dramatic decrease in viraemia and liver DHBV cccDNA (below 0.

Impact of highly active antiretroviral therapy (HAART) on the natural history of hepatitis B virus (HBV) and HIV coinfection: relationship between prolonged efficacy of HAART and HBV surface and early antigen seroconversion.

Background: Coinfection with hepatitis B virus (HBV) in human immunodeficiency virus (HIV)-infected patients is common. However, little is known about the natural history of chronic hepatitis B in HIV-infected populations, especially the impact of highly active antiretroviral therapy (HAART) on the outcome of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) status.

Methods: The characteristics of 92 patients coinfected with HIV and HBV were retrospectively assessed before and after HAART and lamivudine treatment to determine the impact of treatment on chronic hepatitis B and factors associated with HBeAg and/or HBsAg seroconversion.

Progression to cirrhosis in hepatitis C patients: an age-dependent process.

Background: Age at infection is known to be associated with disease progression rate in hepatitis C virus (HCV) infected patients. The aim of this study was to assess when cirrhosis is expected to occur according to host and viral factors.

Methods: Fibrosis progression was studied in 247 naive HCV patients using multiple regression analysis.

Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo.

Background/aims: Hepatocellular carcinoma (HCC) is known to be chemoresistant to anticancer drugs due to the multidrug resistant (MDR) transporters expression. Here, we compared in vitro and in vivo the anti-tumor efficacy of doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles (PIHCA-Dox) versus free doxorubicin (Dox). These nanoparticles are known to overcome the MDR phenotype.

Sustained HBs seroconversion during lamivudine and adefovir dipivoxil combination therapy for lamivudine failure.

We describe the case of a patient with chronic hepatitis B who became resistant to lamivudine and was treated successfully with adefovir dipivoxil in addition to lamivudine. Lamivudine resistance was associated with the selection of a L180M+M204V polymerase mutant. After the addition of adefovir dipivoxil, serum HBV DNA levels dropped by more than 4log(10), which was followed by HBsAg clearance after 22 months of combination therapy.

[Autoimmunization induced by interferon alpha therapy in chronic hepatitis C].

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies.

Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis.

Background: Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders.

Aim: To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin.

Long-term high-dose interferon-alpha therapy delays Hepadnavirus-related hepatocarcinogenesis in X/myc transgenic mice.

The role of interferon-alpha (IFN-alpha) remains unclear in prevention of virus-induced hepatocellular carcinoma in humans. We have investigated it herewith in the X/myc transgenic mouse model of Hepadnavirus-related hepatocarcinogenesis because of upregulation of c-myc oncogene in the liver. We have demonstrated that IFN-alpha can downregulate dose-dependently hepatocyte proliferation and c-myc overexpression at early premalignant stages, while it does not affect either hepatocyte apoptosis or telomerase activity at these steps.

[Early treatment of acute hepatitis C with interferon alpha-2b or interferon alpha-2b plus ribavirin: study of sixteen patients].

Aim Of The Study: To assess the mode of transmission and the efficacy of antiviral therapy in the outcome of treated and untreated patients with acute hepatitis C.

Patients And Methods: From December 1995 to January 2001, 16 consecutive patients and their response to therapy were studied, including clinical, biochemical, virological and histological data.

Results: Hepatitis C virus (HCV) exposure was IVDU (38%), needle-stick injury (19%), medical procedure (6%), piercing (6%), suspected sexual contact (19%), and unknown in 2.

Antiviral effect of adefovir in combination with a DNA vaccine in the duck hepatitis B virus infection model.

Background/aims: Combination of antiviral drugs with immunotherapeutic approaches may be a promising approach for the treatment of chronic hepatitis B. We used the duck HBV (DHBV) infection model to evaluate the efficacy of the combination of adefovir with DNA-immunization by comparison with the respective monotherapies.

Methods: Pekin ducks chronically infected with DHBV received adefovir treatment alone or in association with intramuscular immunization with a plasmid (pCI-preS/S) expressing the DHBV large envelope protein.

Experimental transfection of Macaca sylvanus with cloned human hepatitis B virus.

Due to the absence of easily accessible animal models for the study of hepatitis B virus (HBV), the possibility of using Macaca sylvanus, a monkey originating from Morocco, North Africa, was investigated. Three monkeys were intrahepatically inoculated with a replication-competent head-to-tail HBV DNA plasmid dimer construct. The HBV surface antigen and HBV DNA were detected prior to alanine aminotransferase elevation in the serum of two of three HBV-inoculated monkeys at day 2 post-transfection and persisted for several weeks.