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

Amino Acid Sequence ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferons ; pharmacology ; therapeutic use ; Viral Nonstructural Proteins ; chemistry ; drug effects ; genetics

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*

Alanine Transaminase ; blood ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; immunology ; virology ; Humans ; RNA, Viral ; blood

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.
Antiviral Agents/*therapeutic use ; Drug Resistance, Viral ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; Recurrence ; Ribavirin/therapeutic use ; Sofosbuvir/therapeutic use

Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; Ribavirin ; administration & dosage ; Treatment Outcome

Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

Adult ; Complementarity Determining Regions ; genetics ; Female ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged

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

OBJECTIVETo investigate the influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C.

METHODSThe genotypes of HCV virus were determined in the patients enrolled into the Randomized, opened and controlled trial of Peg-IFN alpha-2a (Pegasys) treatment, controlled with IFN-alpha-2a (Roferon-A), on chronic hepatitis C patients in China. The serum ALT levels and HCV RNA concentration of the patients were detected in the time of before treatment, the end of therapy and follow-up. The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C was analyzed in intention to treat (ITT) population.

RESULTSThe HCV genotypes of 202 cases were determined. 158 (78.2%) cases infected with genotype 1 HCV and 44 (21.8%) cases with genotype non-1. For overall patients, the viral response at the end of treatment (ETVR) and sustained viral response (SVR) rates were 53.8% and 25.3% respectively in patients with genotype 1 HCV, but in genotype non-1 patients those was 61.4% and 43.2%, and the difference of SVR between genotype 1 and non-1 was significant (P=0.021). After grouped by the used drugs, in the patients given Pegasys treatment, the ETVR rates of patients with genotype 1 and non-1 HCV infection were 76.8% and 81.0%, the difference was not significant (P=0.686), but the difference of SVR rates, which were 35.4% and 66.7%, of the patients was significant (P=0.01). The viral relapse rate of genotype 1 was 55.6%; it was significant higher than that of genotype non-1 (23.5%) (P=0.02). In Roferon-A group, the ETVR and SVR rates of patients with genotype 1 HCV were 29.0% and 14.5%, which were lower, but not significant, than those of patients with genotype non-1 (43.5% and 21.7%). The viral relapse rate of genotype 1 was 72.7% and higher, but not significant, than that of genotype non-1 also (50.0%) (P=0.21).

CONCLUSIONHCV genotype could affects the efficacies, mainly the sustained responses, of IFN treatment of patients with chronic hepatitis C, and the effects of IFN were related to the kinds of drugs and therapeutic course.

Antiviral Agents ; therapeutic use ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; Recurrence