OBJECTIVEThe aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle.

DATA SOURCESThis review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication".

STUDY SELECTIONArticles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review.

RESULTSIron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein.

CONCLUSIONThe growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

Female ; Hepacivirus ; pathogenicity ; Hepatitis C ; complications ; metabolism ; Hepcidins ; metabolism ; Humans ; Iron Overload ; etiology ; metabolism ; virology ; Male ; Signal Transduction

BACKGROUNDIt has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-naÏve GT1b CHC patients.

METHODSDirect sequencing and ultra-deep sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum samples of treatment-naÏve patients infected with genotype 1b hepatitis C virus (HCVs).

RESULTSOne hundred and sixty CHC patients were studied. Complete sequence information was obtained for 145 patients (NS3), 148 patients (NS5A), and 137 patients (NS5B). Treatment-failure associated variants of DAAs were detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor); 10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.

CONCLUSIONSThe majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work.

Adult ; Aged ; Antiviral Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; China ; Drug Resistance, Viral ; genetics ; Female ; Fluorenes ; therapeutic use ; Genotype ; Hepacivirus ; drug effects ; pathogenicity ; Hepatitis C ; drug therapy ; High-Throughput Nucleotide Sequencing ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Simeprevir ; therapeutic use

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.
Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Hepatocellular/*etiology ; Hepacivirus/genetics/*pathogenicity ; Hepatitis C/complications/pathology/virology ; Humans ; Liver Neoplasms/*etiology ; Risk

OBJECTIVETo review the updated research on direct antiviral agents (DAAs)-including regimens for hepatitis C virus (HCV), and focus on "difficult-to-treat" HCV-infected patients.

DATA SOURCESThe literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.

STUDY SELECTIONData from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.

RESULTSIt was recognized that some "difficult-to-treat" patients would still exist, even though stronger treatments using such as DAAs, including telaprevir and boceprevir, which lead to higher sustained virological response rates, are available. Such patients include those with advanced fibrosis/cirrhosis, elderly persons, children, HCV-human immunodeficiency virus co-infected patients, HCV-infected recipients, and so on.

CONCLUSIONSCertain "difficult-to-treat" patients would still exist, even though stronger treatment is available. Although evidence from clinical trials is still lacking, interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.

Antiviral Agents ; pharmacology ; therapeutic use ; Hepacivirus ; drug effects ; pathogenicity ; Hepatitis C, Chronic ; drug therapy ; Humans

Adult ; Anti-HIV Agents ; therapeutic use ; Familial Primary Pulmonary Hypertension ; HIV ; pathogenicity ; Hepacivirus ; pathogenicity ; Hepatitis B virus ; pathogenicity ; Humans ; Hypertension, Pulmonary ; drug therapy ; virology ; Male ; Sulfonamides ; therapeutic use

Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune demyelinating disease of the central nervous system, which typically follows acute viral or bacterial infection or vaccination. We report a case of ADEM associated with hepatitis C virus (HCV) infection with positive serum and cerebrospinal fluid (CSF) anti-HCV antibody. After steroid treatment, neurologic symptoms were improved. Virus triggers autoimmunity or direct viral invasion plays a part in the genesis of ADEM. This is the first reported case of ADEM with anti-HCV antibody in the CSF.
Encephalomyelitis, Acute Disseminated/*diagnosis/drug therapy/etiology/virology ; Female ; Hepacivirus/pathogenicity ; Hepatitis C/*complications ; Humans ; Methylprednisolone/therapeutic use ; Middle Aged

This paper investigated the envelope protein E1/E2 quasispecies genetic characterization of 4 HCV positive sera (Genotype 1b: 274, 366, 383; Genotype 2a: 283) in China. Nucleotide acid was extracted and glycoprotein E1/E2 (191-764aa) coding genes were obtained by RT-PCR, positive clones were randomly selected for sequencing. The phylogenetic relationships and the homology of nucleotide and amino acid were analyzed based on E1/E2 coding genes, and some vital functional regions of E1/E2 were characterized. A total of 43 sequences (274: 10; 283: 12; 366: 13; 383: 8) were obtained showing high genetic heterogeneity in HVR1 and HVR2 regions, while sequences of the neutralizing epitopes, transmembrane domain I, II and N-terminal ectodomain were comparatively conservative. Single base (C) insertion mutation at nt1279 ( E1 region, aa313), resulting in a mutated E1 coding protein (beginning at aa 313) and interruption at N terminus (aa 398) of HVR1 region of E2, was dominant quasispecies sequence(11/12) found in serum 283 . This is the first report on E1/E2 quasispecies in Chinese HCV patients and this novel pattern of insertion mutation provides important information for further study on HCV pathogenesis and immune evasion.
Amino Acid Sequence ; Base Sequence ; DNA Mutational Analysis ; Hepacivirus ; genetics ; pathogenicity ; Hepatitis C ; virology ; Humans ; Molecular Sequence Data ; Mutagenesis, Insertional ; Viral Envelope Proteins ; chemistry ; genetics

BACKGROUNDAn epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established. This study was designed to investigate the prevalence of type 2 diabetes mellitus and insulin resistance, and to explore the relation between insulin resistance and hepatitis C virus genotype, serum hepatitis C virus-RNA level in chronic hepatitis C (CHC) patients.

METHODSThree hundred and fifty-nine consecutive patients (CHC, n = 296; chronic hepatitis B (CHB), n = 63) were evaluated. HCV genotyping was performed by restriction fragment method and serum hepatitis C virus-RNA quantified PCR for all CHC patients in the baseline serum. Fasting levels of insulin and glucose were measured in all patients and the homeostatic assessment of insulin resistance was calculated in the baseline serum.

RESULTSType 2 diabetes mellitus was diagnosed in 15.5% of 296 CHC patients. Insulin resistance was present in 23.8% of the 235 nondiabetic CHC patients, in 23.1% of the 182 nondiabetic and noncirrhotic CHC patients, and associated with high serum HCV RNA level (OR: 1.754; 95%CI: 1.207 - 2.548, P = 0.003) and age > 40 years (OR: 3.542; 95%CI: 1.257 - 9.978, P = 0.017). Insulin resistance was less frequent in CHB than in matched CHC (7.9% vs. 21.4% respectively, P < 0.0001).

CONCLUSIONThe incidence of insulin resistance in CHC was significantly higher than that in CHB patients, associated with high serum HCV RNA level and age > 40 years.

Adult ; Aged ; Blood Glucose ; metabolism ; China ; Diabetes Mellitus, Type 2 ; blood ; metabolism ; virology ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; pathogenicity ; Hepatitis C, Chronic ; blood ; metabolism ; virology ; Humans ; Insulin ; blood ; Insulin Resistance ; genetics ; physiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Viral ; genetics ; Risk Factors

Antiviral Agents ; therapeutic use ; Glomerulonephritis ; drug therapy ; virology ; Hepacivirus ; drug effects ; pathogenicity ; Humans ; Interferons ; therapeutic use ; Liver Cirrhosis ; complications ; virology ; Male ; Middle Aged ; Ribavirin ; therapeutic use

Hepacivirus ; pathogenicity ; Hepatitis C ; virology ; Receptors, Virus