Hepatitis C Virus Clearance Rate Research Articles

What Have We Learned from Studies of IFN-λ Variants and Hepatitis C Virus Infection?

Chronic infection with the hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In 2009, genome-wide association studies (GWAS) strongly linked genetic variants in the interferon lambda (IFN-λ) chromosomal region to HCV clearance. In 2013, discovery of the IFNL4 gene provided a functional explanation for those GWAS findings. The IFNL4-ΔG/TT (rs368234815) variant controls generation of the IFN-λ4 protein. Paradoxically, the IFNL4-TT allele, which abrogates IFN-λ4, associates with higher rates of spontaneous HCV clearance and better response to treatments for HCV infection. The finding that a "knock-out" allele for IFN-λ4 enhances HCV clearance challenges the paradigm of IFNs as antiviral cytokines. Genetic variants in the IFN-λ region have also been associated with hepatic inflammation and fibrosis from various etiologies, however, alleles that are linked with improved HCV clearance associates with worse inflammation and fibrosis. These studies demonstrate that GWAS of infectious diseases may yield important and unexpected biological insights.

Approaches, Progress, and Challenges to Hepatitis C Vaccine Development

Risk factors for hepatitis C virus (HCV) infection vary, and there were an estimated 1.75 million new cases worldwide in 2015. The World Health Organization aims for a 90% reduction in new HCV infections by 2030. An HCV vaccine would prevent transmission, regardless of risk factors, and significantly reduce the global burden of HCV-associated disease. Barriers to development include virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses. Although highly effective vaccines could prevent infection altogether, immune responses that increase the rate of HCV clearance and prevent chronic infection may be sufficient to reduce disease burden. Adjuvant envelope or core protein and virus-vectored nonstructural antigen vaccines have been tested in healthy volunteers who are not at risk for HCV infection; viral vectors encoding nonstructural proteins are the only vaccine strategy to be tested in at-risk individuals. Despite development challenges, a prophylactic vaccine is necessary for global control of HCV.

Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination.

The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P<0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.

Depression, fatigue and neurocognitive deficits in chronic hepatitis C.

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection

Hepatitis C virus (HCV) is a global health problem, because infection frequently leads to chronic hepatitis C eventually progressing to liver cirrhosis and liver cancer. Improved insights into the HCV replication cycle and the role of HCV non-structural proteins have recently enabled to identify drugs directly acting on specific HCV target structures. Agents from three drug classes have been developed and approved by the health authorities. Combinations of two or more drugs from different classes achieve high (>90%) HCV clearance rates and are well tolerated. This interferon-free DAA (direct antiviral agent) therapy has revolutionized antiviral therapy in hepatitis C so that successful hepatitis C treatment can be offered to virtually all patients irrespective of their co-morbidity. This review provides an overview over currently approved regimens and outlines their use in clinical practice. In addition potential short-comings of the current therapeutic options such as drug-drug interactions and selection of viral resistance are addressed. DAA combination therapy has the potential to obtain global control over hepatitis C. However, easy access to DAAs, availability of reliable HCV diagnostics, and affordable costs remain still important goals, which must be reached to globally eliminate hepatitis C.

Confounding by Single Nucleotide Polymorphism rs117648444 (P70S) Affects the Association of Interferon Lambda Locus Variants with Response to Interferon-α-Ribavirin Therapy in Patients with Chronic Genotype 3 Hepatitis C Virus Infection

Genome-wide association studies discovered interferon lambda (IFNL or IFN-λ) locus on chromosome 19 to be involved in clearance of chronic hepatitis C virus (HCV) infection in patients following interferon-α-ribavirin (IFN-RBV) therapy. Subsequent studies established a dinucleotide polymorphism rs368234815, as the prime causal variant behind this association. The ΔG allele of this variant gives rise to a new IFNL gene, IFNL4, coding for IFN-λ4 whose activity paradoxically associates with lesser viral clearance rates. A low-frequency, nonsynonymous single nucleotide polymorphism (SNP) rs117648444 within the 2nd exon of IFNL4 changes the 70th amino acid from proline to serine resulting in lower activity of the functional IFN-λ4 protein, thereby increasing HCV clearance rates. In the present study, we used a cohort of genotype 3 HCV-infected patients, drawn from different geographical regions of India who underwent IFN-RBV therapy, to examine the association of several important IFNL locus SNPs/variants with sustained virological response (SVR). Intriguingly, the causal variant rs368234815 did not show the best strength and significance of association with SVR, while further analysis revealed that a negative confounding effect of rs117648444 was responsible for this phenomenon. Our results indicate that IFNL locus SNPs are subject to either a positive or a negative confounding effect by rs117648444; the nature of confounding depends on the linkage of the IFNL SNPs with the low-activity IFN-λ4-generating minor allele of rs117648444. Thus, our work demonstrates that the linkage disequilibrium structure of the IFNL region may confound the results of association studies. These results have implications for the design and understanding of future case-control studies involving IFNL locus SNPs/variants.

Polymorphisms near the IFNL3 Gene Associated with HCV RNA Spontaneous Clearance and Hepatocellular Carcinoma Risk.

The aims of this study were to investigate associations between single nucleotide polymorphisms (SNPs) near the genes IFNL2, IFNL3, and IFNL4 and spontaneous clearance of hepatitis C virus (HCV) and to evaluate variants for their risk of hepatocellular carcinoma (HCC) among subjects in whom spontaneous HCV RNA clearance did not occur. In the first study, 889 untreated anti-HCV-seropositive patients without HCC symptoms were followed from 1991 to 2005. The spontaneous HCV clearance rate was found to be 33.1%. The TT variant of rs8099917 near IFNL3 was associated with increased spontaneous HCV RNA clearance, with an adjusted odds ratio (95% CI) of 2.78 (1.43–5.39), as was the newly-identified TT/TT dinucleotide variant rs368234815 near IFNL4 (adjusted odds ratio 2.68, 95% CI: 1.42–5.05). In the second study, associations between SNPs and HCC risk were examined in 483 HCC cases with detectable HCV RNA and 516 controls. In participants with HCV genotype 1, unfavorable genotypes for HCV clearance near IFNL3were associated with increased HCC risk, the adjusted odds ratio (95% CI) for rs12979860 and rs8099917 being 1.73 (1.00–2.99) and 1.84 (1.02–3.33), respectively. Host characteristics should be considered to identify high-risk patients to prioritize the use of new antiviral agents and intensive screening.

Influence of HIV infection on hepatitis C progress in patients co-infected with HIV/HCV

To understand the influence of HIV infection on hepatitis C progress in patients co-infected with HIV and hepatitis C virus (HCV) and related immune mechanism. Twenty eight patients co-infected with HIV/HCV and 12 patients with simplex HCV infection were enrolled. The liver function and hepatic fibrosis progress were evaluated by detecting peripheral blood and with Fibro-Scan. The viral load of HCV was detected by using real time quantitative PCR. And the percentage of Treg/CD4⁺ T lymphocyte cell was tested by using flow cytometry. The levels of ALT and ALP in HIV/HCV co-infection group were (76.16 ± 81.248) U/L, (24.507 1 ± 8.194) g/L respectively, higher than those of simplex HCV infection group [(27.475 0 ± 13.985) U/L, (16.966 7 ± 7.189) g/L], the differences were statistical significant. P value was 0.012 and 0.009 respectively. The liver fibrosis index in HIV/HCV co-infection group was 5.950 0-5.825 0 Kpa, higher than that in simplex HIV infection group (5.150 0-1.050 0 Kpa), and the difference was nearly statistical significant (P = 0.077). The HCV viral load in HIV/HCV co-infection group was (6.476 8-5.343 4) lg copy/ml, higher than that in simplex HCV infection group [(1.699 0-2.681 5) lg copy/ml], and the rate of HCV clearance in HIV/HCV co-infection group was 32.14%, lower than that in simplex HCV infection group (75.00%). P value was 0.012 and 0.032 respectively. The percentage of Treg/CD4⁺ T lymphocyte cell in HIV/HCV co-infection group was (7.460 0%-2.287 5%), higher than that in simplex HCV infection group (5.965 0%-2.105 0%), and the difference was significant (P = 0.032). The percentage of Treg/CD4⁺ T lymphocyte cell was significantly related with HCV viral load (ρ = 0.350, P = 0.027), and HCV viral load was significantly related with the liver fibrosis index (ρ = 0.487, P = 0.001). HIV infection could accelerate the progress of hepatitis C, and Treg cells were involved in this progress.

Prevalence and management of chronic hepatitis C virus infection in women.

Hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States and is a leading cause of cirrhosis, need for liver transplantation, and liver-related mortality in women. Women should be offered testing if they fall in a high-risk group for exposure. Compared to men, women have higher rates of spontaneous HCV clearance after exposure and slower progression to cirrhosis but are more susceptible to liver damage from comorbid alcohol use. Premenopausal women with HCV should be counseled about the risks of antiviral treatment during pregnancy and the potential for vertical transmission of HCV to their offspring.

Natural clearance of hepatitis C virus in 96 patients with infection acquired by blood transfusion from a single donor in Guizhou

To investigate the clinical features and rate of natural viral clearance in patients with hepatitis C virus (HCV) infection acquired by blood transfusion from a single donor. Ninety-six patients who acquired HCV infection between January 1998 and December 2002, upon receipt of donated blood from a single infected individual in Guizhou,were included in this retrospective cross-sectional study. Patients were clinically assessed to determine levels of anti-HCV antibodies, HCV RNA and biochemical indicators of liver function,as well as features of liver structure (by abdominal B ultrasonography and elastography). HCV genetic testing was used to determine the virus genotype. Measurement data were expressed as mean ± standard deviation. Count data were analyzed by the x² test,with P less than 0.05 indicating statistical significance. All 96 patients tested positive for antiHCV antibodies. The majority of patients (70%; 34:33 male:female) had HCV RNA more than or equal to 1.0 * 103 copies/ml. All patients carried the same HCV genotype as the single blood donor:genotype lb. The overall rate of natural HCV clearance was 30.2%. but males had a significantly lower rate (19.0% (8/42) vs. females:38.9% (21/54);x²=4.41,P=0.023) as did older patients (more than 40 years-old:16.1% (5/31) vs .less than or equal to 40 years-old:36.9% (24/65);x²=4.30,P=0.028). The overall rate of chronic HCV infection (CHC) was 69.8%,but the rate was significantly lower in younger patients (less than or equal to 40 years-old:63.1% (41/65) vs. more than 40 years-old:83.9% (26/31);x²=6.67,P=0.028). Among the 67 patients with CHC,12 had symptoms of mild weakness,anorexia and abdominal distention,11 had elevated serum alanine aminotransferase (116.25 +/- 24.65 U/L) and stage 3 or 4 fibrosis (liver elasticity values more than or equal to 5.1 kPa),and three had mildly abnormal serum bilirubin (32.56 ± 5.28 mumol/L). Fifteen patients showed signs of chronic hepatitis and one patient showed signs of cirrhosis by abdominal B ultrasonography. None of the patients showed signs of hepatocellular carcinoma. The course of blood transfusion acquired HCV infection is largely unknown and natural viral clearance rate may be associated with sex-and age-related factors.

Interleukin‐28B genetic variations and spontaneous clearance of hepatitis C antibody–positive blood donors in China

Single-nucleotide polymorphisms (SNPs) near the interleukin (IL)28B gene have been shown to be associated with spontaneous clearance of hepatitis C virus (HCV) infection in western populations. Anti-HCV-reactive and HCV RNA-negative samples were often found in Chinese blood donors. This study was to determine whether the IL28B gene variant is also associated with the natural outcome of HCV infection in Chinese blood donors. A total of 111 anti-HCV-negative blood donors and 100 anti-HCV-reactive subjects were enrolled in this study. HCV-infected blood donors were classified into spontaneous clearance group and chronic infection group through HCV RNA detection. IL28B genetic variations (rs8099917 and rs12979860) were genotyped by polymerase chain reaction and direct sequencing. A total of 24 (24.0%) donors spontaneously cleared HCV. The rs12979860 C allele frequency was 90.3% and the rs8099917 T allele frequency was 96.7% in our study. The rs12979860 CC genotype was strongly associated with spontaneous HCV clearance. Female blood donors had a higher rate of spontaneous HCV clearance than male donors (15/42 [35.7%] vs. 9/58 [15.5%], p = 0.02). The rs12979860 CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV in Chinese blood donors and female donors are more likely to clear HCV infection than male donors.

Treatment of Chronic Hepatitis C in a Canadian Aboriginal Population: Results from the Prairie Study

The Aboriginal population of Canada is at increased risk of exposure to the hepatitis C virus (HCV). Previous data indicate that spontaneous clearance of HCV occurs more often in Aboriginals than Caucasians. Whether this enhanced response extends to antiviral therapy for chronic HCV remains to be determined. To document and compare the biochemical and virological responses to antiviral therapy in HCV-infected Canadian Aboriginals and Caucasians. A total of 101 treatment-naive adult patients (46 Aboriginal, 55 Caucasian) with chronic HCV genotype 1 infections were prospectively treated with pegylated-interferon and ribavirin and followed as per national guidelines. Aboriginals had higher HCV-RNA loads at baseline (6.42log(10) versus 5.98log(10); P<0.03). Although normalization of serum aminotransferase levels, decreases in viral loads, and rapid, early and end-of-treatment virological responses were similar in the two cohorts, sustained virological responses were significantly lower in Aboriginals (35% versus 55%; P=0.047). Premature discontinuation of treatment and⁄or loss of patients to follow-up was common (Aboriginals 37%, Caucasians 27%). Treatment-related side effects were similar in the two cohorts. Despite higher rates of spontaneous HCV clearance, the response to antiviral therapy was similar, if not lower, in Aboriginals compared with Caucasians with chronic HCV genotype 1 infections. Compliance with treatment is an issue that needs to be addressed in the management of these patients.

African Americans Are Less Likely to Have Clearance of Hepatitis C Virus Infection

Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. African Americans are known to have a higher prevalence of HCV and lower response to anti-HCV therapy. The aim of this study is to assess the differences in the prevalence of chronic HCV infection in according to patients' ethnic background. We used the recent National Health and Nutrition Examination Survey with extensive clinical and laboratory data. Active HCV infection was defined as having HCV-positive antibody with detectable HCV RNA by polymerase chain reaction. HCV clearance was defined as HCV-positive antibody with negative HCV RNA. Clinico-demographic data were compared between anti-HCV positive individuals with or without HCV clearance. The stratum-specific χ test for independence was used. Logistic regression was used to identify independent predictors of HCV clearance. P-values ≤0.05 were considered statistically significant. All analyses were run using SAS 9.1 and SUDAAN 10.0. The cohort included 14,750 adults (age 47.6 ± 0.75 y, 64% white, 21% African American, 10% Hispanics, and 63% male). Of these, 1.32 ± 0.11% were anti-HCV positive with 75.94 ± 4.72% having active HCV viremia. The only parameter significantly different between those who did or did not clear HCV was the proportion of African Americans: 8.0 ± 3.7% versus 24.9 ± 5.0%, P=0.0163. Indeed, the rate of HCV clearance was lowest among African Americans (9.3 ± 3.5%) as compared with both whites (27.2 ± 6.5%) and Hispanics 31.2 ± 9.1% (P<0.05). In multivariate analysis, the only independent predictor of active HCV infection was African American race: odds ratio (95% confidence interval)=3.80 (1.31-11.06), P=0.0151. African Americans not only have lower response to anti-HCV therapy but also are less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV.

Human immunodeficiency virus enhances hepatitis C virus replication by differential regulation of IFN and TGF family genes

HIV co-infection significantly impacts the natural history of hepatitis C virus (HCV) by increasing plasma HCV viral load, accelerating liver disease progression, and reducing rates of HCV clearance. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the impact of HIV on cytokine expression is unknown. In this study, an HCV continuous infection cell culture system was modified to permit co-infection with HIV to test the hypothesis that virus-induced disregulation of immune-response genes, particularly interferons and TGF-β, may create a permissive environment for the initial establishment of HIV/HCV co-infection in the host. CCR5-expressing Huh-7.5 hepatoma cells were transduced with human CD4 antigen to allow HIV infection in vitro. Co-infection of CD4⁺ Huh-7.5 cells with HIV and HCV or co-culture of HIV-infected CD4⁺ Huh-7.5 cells and HCV-infected Huh-7.5 cells increased the level of HCV RNA compared to HCV mono-infection. Quantitative gene expression analysis revealed HIV-induced up regulation of most tested IFN family genes when compared to HCV or co-infection. HCV infection induced up regulation of many TGF family genes that were subsequently down-regulated in the presence of HIV or HIV/HCV. Interestingly, co-infection resulted in down regulation of several IFN genes and significant up regulation of TGF-β genes leading to an overall enhancement of HCV replication. These data suggest that HIV infection may influence HCV replication in vitro by increasing levels of HCV RNA, possibly through the differential regulation of endogenous IFN and TGF family genes.

IL28B genetic variants and gender are associated with spontaneous clearance of hepatitis C virus infection

Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV-infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY(®) SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07-112.50), 14.88 (2.02-109.72), 7.92 (1.88-33.32) and 2.32 (1.22-4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9-2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.

Correlates of spontaneous clearance of hepatitis C virus in a Danish human immunodeficiency virus type 1 cohort

Around a quarter of individuals infected with hepatitis C virus (HCV) are spontaneously able to clear the virus. Correlates of spontaneous HCV clearance are not well established and the aim of this study was to characterize factors associated with spontaneous HCV clearance in a human immunodeficiency virus (HIV)-co-infected cohort. We analyzed 327 anti-HCV-positive HIV-1-infected patients using multivariate logistic regression. HCV clearance was defined as the presence of anti-HCV with undetectable HCV RNA from at least 2 measurements more than 6 months apart. We included 327 HIV-1-infected individuals, predominantly of Caucasian race; 112 (34%) were females, 258 (79%) were injecting drug users (IDU), 25 (8%) were men who have sex with men (MSM), and 20 (6%) were hepatitis B surface antigen (HBsAg)-positive. Seventy-six (23%; 95% confidence interval (CI) 18-28) had cleared their HCV infection and 251 (77%; 95% CI 72-82) had a chronic infection. The clearance rate in HBsAg-positive individuals was 65%. Being female, HBsAg-positive, or belonging to HIV exposure groups IDU and MSM predicted higher HCV clearance rates (adjusted odds ratio (aOR) 1.8, 95% CI 1-3.2; aOR 7.6, 95% CI 2.7-21; aOR 5.2, 1.2-23.5; and aOR 10.2, 95% CI 1.8-58, respectively). Race, acquired immunodeficiency syndrome (AIDS), and antiretroviral therapy were not associated with HCV clearance. The HCV clearance rate in this HIV-1 cohort was 23%. MSM and IDUs may have higher clearance rates due to their repeated exposure to low-dose HCV, leading to immune memory. Our data suggest an interaction of hepatitis B virus and HCV that influences the outcome of acute HCV infection.

Interleukin‐28B polymorphisms are associated with hepatitis C virus clearance and viral load in a HIV‐1‐infected cohort

Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP) of the interferon-λ3 coding interleukin (IL)-28B gene to study the relationship between IL28B SNPs and outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed chronic infection. The exonic rs8103142 CT, the promoter rs12979860 CT and the intronic rs11881222 AG genotypes were associated with a decreased HCV clearance rate with adjusted odds ratios (aOR) of 0.3 (95% CI, 0.1-0.7), 0.4 (95% CI, 0.2-0.8) and 0.4 (95% CI, 0.2-0.8), respectively. The haplotype block TCG CTA was associated with a decreased HCV clearance rate (aOR 0.4, 95% CI, 0.2-0.8). Further, we found significant differences in HCV RNA levels among individuals chronically infected with HCV genotype 1 for rs8103142 and rs12979860 (P ≤ 0.05). Chronically infected individuals with HCV genotype 3 and with the favourable haplotype block CTA CTA had higher median HCV RNA levels than individuals with unfavourable haplotype blocks (P ≤ 0.05). Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence the outcome of HCV infection.

Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: The HEPAIG study

Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log(10) IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype.

Pegylated Interferon Alfa‐2a Monotherapy for Hemodialysis Patients with Acute Hepatitis C

Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C. From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 microg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal. The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P < .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received >12 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up. Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy.

Hepatitis C infection in HIV-1 natural viral suppressors

HIV-1 natural viral suppressors (NVSs) demonstrate an intrinsic ability to control HIV-1 replication in the absence of antiretroviral therapy. The objective of this study was to investigate whether HIV-infected NVSs also demonstrate enhanced ability to control hepatitis C virus (HCV) infection, and whether HCV infection in the NVSs affects the degree of HIV control. A cross-sectional study was undertaken to compare HCV-related parameters in the NVS to the two race-matched cohorts (HIV/HCV-coinfected or HCV-monoinfected patients). Within the NVS, HIV-related parameters were compared based on the presence or absence of chronic HCV. NVS patients had a significantly higher clearance rate of HCV at 23.3% (seven of 30), compared to the 6.5% (23 of 350) of HIV/HCV-coinfected and 9.1% (32 of 350) of HCV-monoinfected patients (P = 0.005 and P = 0.024, respectively). Apart from the HCV clearance rate, there was no significant difference in HCV-related parameters such as HCV viral load or liver histology in the NVS with chronic HCV compared to HCV/HIV-coinfected patients or HCV-monoinfected patients. However, NVS patients with chronic HCV infection had statistically significant lower CD4 cell count and CD4%, and lower CD4/CD8 ratio compared to those NVSs without chronic HCV infection (P = 0.029, P = 0.046, and P = 0.062, respectively). It appears that some NVS patients have the ability to effectively control multiple agents that can cause chronic viral infections. In addition, it appears that the presence of chronic HCV infection within the NVS adversely affects immunological parameters.