Female ; Glucuronosyltransferase ; biosynthesis ; genetics ; Hepatitis B, Chronic ; enzymology ; Hepatitis C, Chronic ; enzymology ; Hepatitis, Chronic ; enzymology ; Humans ; Liver Cirrhosis ; enzymology ; Male ; RNA, Messenger ; biosynthesis ; genetics

Hepacivirus ; genetics ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; therapy ; Hepatitis C ; therapy ; Humans ; RNA Interference ; RNA, Small Interfering ; genetics ; RNA, Viral ; physiology ; Virus Replication ; genetics

Animals ; Carcinoma, Hepatocellular ; genetics ; virology ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Neoplasms ; genetics ; virology ; Neoplasm Recurrence, Local ; genetics ; Point Mutation ; Telomerase ; metabolism

OBJECTIVETo investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.

METHODSEleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.

RESULTSA total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.

CONCLUSIONDue to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.

Animals ; Fatty Liver ; complications ; genetics ; metabolism ; virology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis C, Chronic ; complications ; genetics ; metabolism ; virology ; Humans

Anemia ; chemically induced ; Hepatitis C, Chronic ; drug therapy ; genetics ; Humans ; Polymorphism, Genetic ; Pyrophosphatases ; genetics ; Ribavirin ; adverse effects ; therapeutic use

Viral hepatitis C is one of the important causes of liver cirrhosis and hepatocellular carcinoma. There are approximately 10 million cases of chronic hepatitis C virus (HCV) infection in China. However, over 70% of HCV infections of China have not yet been detected. According to the goal of "eliminating viral hepatitis as a public health threat by 2030" of the World Health Organization Viral Hepatitis Strategy, and the fact that medical institutions remain the main places for detecting HCV infections or patients in China at present, we established the " In-hospital process for viral hepatitis C screening and management in China (Draft)", with intention to promote the multidisciplinary collaboration and cooperation among the departments of clinic, laboratory, infection control, management, and etc. in medical institutions, and strengthen consultation and referral of patients with detected HCV antibodies and advance the diagnosis and antiviral treatment of patients with chronic hepatitis C.
Antiviral Agents/therapeutic use* ; China/epidemiology* ; Hepacivirus/genetics* ; Hepatitis C/epidemiology* ; Hepatitis C, Chronic/epidemiology* ; Hospitals ; Humans ; Liver Neoplasms/drug therapy*

Genotype ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Parvoviridae Infections ; complications ; virology ; Parvovirus ; classification ; genetics ; isolation & purification ; Parvovirus B19, Human ; isolation & purification

BACKGROUND: Although the polyproteins of hepatitis C virus(HCV) are processed and formed in nearly equimolar amounts, individual functional proteins have a discrepancy in their time of appearance following HCV infection and eliciting immune response. This study was conducted to compare the reactivity toward regional specific HCV protein in relation to virological characteristics, including HCV genotype and HCV replication. METHODS: Sera from forty-five patients with chronic HCV infection were analyzed through the experiments of the recombinant immunoblot assay(RIBA-2), HCV genotyping and HCV RNA quantitation. RESULTS: The frequencies of seropositivity to C22-3, C33C, C100-3 and 5-1-1 proteins were 91.1+ACU-, 91.1+ACU-, 64.4+ACU- and 53.3+ACU-, respectively, of all the patients, and thus the antibodies to C22-3 and C33C proteins were found more frequently (p +ADw- 0.05). The antibody responses between core or NS3 proteins and NS4 proteins showed more discrepancy in the HCC group than that in the CH group, implying a possibility of oncogenic potential of core or NS3 gene in hepatocarcinogenesis. The detection rate of antibodies to C22-3 and C33C, in accordance with serum HCV RNA levels, was significantly higher in highly viremic patients than that in low viremic patients (p +ADw- 0.05). Antibodies to C22-3, C33C, C100-3 and 5-1-1 were also found more frequently in patients with HCV genotype 1b, compared to those with HCV genotype 2a (p +ADw- 0.05). CONCLUSION: These results suggest that antibody detection of HCV may depend on the virological characteristics of HCV, the levels of HCV replication and HCV genotype and, therefore, HCV RNA detection using RT-PCR technique is essential for confirmatory diagnosis for HCV infection. Furthermore, the HCV core or NS3 Protein may play important role in hepatocarcinogenesis.
Adult ; Aged ; Female ; Genotype ; Hepatitis C Antibodies/blood+ACo- ; Hepatitis C, Chronic/virology ; Hepatitis C, Chronic/immunology+ACo- ; Hepatitis C-Like Viruses/physiology ; Hepatitis C-Like Viruses/genetics ; Human ; Male ; Middle Age ; RNA, Viral/blood ; Viral Core Proteins/immunology+ACo- ; Viral Nonstructural Proteins/immunology+ACo- ; Virus Replication

Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment.
Adult ; Aged ; Amino Acid Sequence ; Antiviral Agents/therapeutic use* ; Base Sequence ; Carcinoma, Hepatocellular/virology* ; Carcinoma, Hepatocellular/blood ; Codon ; Female ; Genotype ; Hepatitis C, Chronic/virology* ; Hepatitis C, Chronic/drug therapy* ; Hepatitis C, Chronic/blood ; Hepatitis C-Like Viruses/isolation & purification ; Hepatitis C-Like Viruses/genetics* ; Hepatitis C-Like Viruses/classification ; Human ; Interferon-alpha/therapeutic use* ; Liver Neoplasms/virology* ; Liver Neoplasms/blood ; Male ; Middle Age ; Molecular Sequence Data ; Mutation* ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction