Prevalence and risk factors for Hepatitis C and HIV-1 infections among pregnant women in Central Brazil

Background  

Hepatitis C (HCV) and human immunodeficiency virus (HIV) infections are a major burden to public health worldwide. Routine antenatal HIV-1 screening to prevent maternal-infant transmission is universally recommended. Our objectives were to evaluate the prevalence of and potential risk factors for HCV and HIV infection among pregnant women who attended prenatal care under the coverage of public health in Central Brazil.     

Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil

Background

The progression of liver disease in patients with chronic hepatitis C virus (HCV) infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literatute. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics.

Methods

Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms.

Results

A total of 283 patients were included; genotype 1 was idenfied in 163 (57.6%) patients, genotype 3 in 112 (39.6%), genotype 2 in 7 (2.5%), and genotype 4 in 1 (0.35%). Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p < 0.05).

Conclusion

Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.

     

Sofosbuvir plus ribavirin with or without peginterferon for the treatment of hepatitis C virus: Results from a phase 3b study in China

Background and Aim

Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6.

Methods

Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12).

Results

Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment‐naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87–98%) for HCV genotype 1 and 97% (95% CI, 84–100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87–99%) for genotype 1, 100% (95% CI, 40–100%) for genotype 6, and 95% (95% CI, 90–98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83–97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment‐unrelated adverse events.

Conclusions

Sofosbuvir‐based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.     

The influence of immunosuppressants on direct‐acting antiviral therapy is dependent on the hepatitis C virus genotype

Background

Direct‐acting antivirals (DAAs) have substantially increased sustained virological response rates after liver transplantation, with improved tolerance compared to interferon‐based therapy. The influence of immunosuppressive agents on the efficacy of DAAs has not been clarified.

Methods

Subgenomic hepatitis C virus (HCV) replicons for genotype (GT) 1b, 2b, 3a, and 4a were treated with the mammalian target of rapamycin (mTOR) inhibitors everolimus and sirolimus or with the calcineurin inhibitors (CNIs) cyclosporine or tacrolimus, either alone or in combination with selected DAAs. Cell proliferation‐related effects were excluded with MTT assays. HCV replication activity was quantified by quantitative real‐time polymerase chain reaction or luciferase assay.

Results

Addition of either mTOR inhibitor to the DAA daclatasvir (DAC) resulted in a 30% increase in antiviral activity compared to DAC alone for HCV GT2a, GT3a, and GT4a (all P ≤ .01). Similar results were obtained using sofosbuvir and ledipasvir. In contrast, addition of either mTOR inhibitor to DAC induced a 30% reduction in antiviral activity in GT1b cells (P ≤ .01 vs DAC alone). Neither CNI affects the antiviral activity of the DAAs in any HCV GT.

Conclusion

For patients with HCV GT2a, GT3a, or GT4a infection, mTOR‐based immunosuppressive therapy may be beneficial. CNI‐based therapy may be more efficacious in GT1b patients, as mTOR inhibitors seem to impair antiviral efficacy of DAAs in HCV GT1b infection.     

Chronic HCV infection is a risk factor of ischemic stroke

Objectives

Cerebrovascular diseases are leading cause of death worldwide. Plaque rupture and embolization account for one-third of ischemic stroke. The causes are not fully known, but inflammation plays a pathogenic role. Recently, HCV infection has been identify as risk of atherosclerosis. HCV replicates within carotid plaques and brain endothelia cells; moreover, HCV patients showed higher levels of inflammation. Thus, we hypothesized that subjects carrying HCV are at higher risk of stroke. Accordingly, we evaluated prevalence and role of HCV infection in patients with stroke.

Methods

A priori sample size was calculated. Overall, 820 consecutive patients were enrolled, 123 with stroke and, as control, 697 age- and gender-matched (295 with COPD; 402 with diseases other than HCV-associated). Patients were evaluated for HCV and conventional risk of stroke.

Results

Prevalence of HCV was higher in patients with stroke than that observed in control (26.8% vs. 6.6%, p = 0.0001). An analysis of stroke patients showed that those HCV positive were younger (p = 0.017) had lower serum levels of cholesterol (p = 0.001), triglycerides (p = 0.045), and higher serum levels of inflammation markers (ESR, p = 0.001; CRP, p = 0.0001; fibrinogen, p = 0.012). A multivariate analysis showed that HCV infection was an independent risk factor of stroke (O.R. 2.04, 95% C.I. 1.69–2.46; p = 0.0001). A secondary analysis showed that HCV patients had higher (p = 0.031) prevalence of past ischemic heart disease.

Conclusions

HCV infected patients are at higher and earlier risk of stroke. Inflammation is a key mediator. Clinicians in clinical practice and researchers in future trials should take into account these new findings.     

Occurrence of late relapse of hepatitis C virus confirmed by molecular analysis after sustained virologic response to interferon–ribavirin‐based therapy

Aim

The optimal duration of follow‐up for patients who achieve sustained virologic responses (SVR) has become an important issue. Reports on long‐term follow‐up of SVR have indicated that 99% of patients maintained SVR. However, the limitations of a majority of studies include small patient numbers, short study periods, and lack of molecular analysis of hepatitis C virus (HCV) genome. The present study sought to evaluate the late relapse rate in long‐term follow‐up of patients who achieved SVR, with molecular analysis of HCV.

Methods

A total of 224 patients with chronic hepatitis C who were treated by interferon and ribavirin‐based therapy and achieved SVR were enrolled. All patients were recommended for follow‐up every 6 or 12 months.

Results

The mean follow‐up period was 6.0 years (range, 1.0–13.6 years). Cumulative 5‐ and 10‐year follow‐up rates of the patients after SVR were 87.8% and 78.8%, respectively. Cumulative 5‐ and 10‐year follow‐up rates of serum HCV RNA after SVR were 85.5% and 52.6%, respectively. Two patients had detectable serum HCV RNA at 20 and 30 months, respectively, after SVR. Phylogenetic analyses of core, non‐structural protein 3, and 5A regions of HCV strains from late relapse patients confirmed the same strain was present at baseline and late relapse.

Conclusions

Two of 224 patients developed late relapse of HCV by the original strain, which was confirmed by direct sequencing analysis. Although few patients may develop late relapse, SVR achieved with interferon and ribavirin‐based therapy is durable for prolonged periods.     

Modelling the force of infection for hepatitis B and hepatitis C in injecting drug users in England and Wales

Background  

Injecting drug use is a key risk factor, for several infections of public health importance, especially hepatitis B (HBV) and hepatitis C (HCV). In England and Wales, where less than 1% of the population are likely to be injecting drug users (IDUs), approximately 38% of laboratory reports of HBV, and 95% of HCV reports are attributed to injecting drug use.     

Formal Patient Education Improves Patient Knowledge of Hepatitis C in Vulnerable Populations

Background  

Hepatitis C (HCV) knowledge is limited in injection drug users (IDU). Vulnerable populations including IDUs are disproportionally affected by HCV. Effective HCV education can potentially reduce disparity in HCV prevalence and its outcome in this population.     

Serum apolipoprotein C-III is independently associated with chronic hepatitis C infection and advanced fibrosis

Background  

The hepatitis C virus (HCV) is known to disrupt lipid metabolism, making serum lipoprotein levels good candidates to explore as markers of HCV disease progression. Assessment of the major apolipoproteins (Apo) and their relationship to hepatic fibrosis remain largely unexplored.     

Distribution of hepatitis C virus genotypes in patients infected by different sources and its correlation with clinical and virological parameters: a preliminary study

Background  

Information about genotypes and associated risk factors in hepatitis C virus (HCV) infected patients in Iran is limited. The aim of this study was to identify the HCV genotypes and associated risk factors in a group of HCV infected patients from Iran.     

Antiviral Treatment of Patients with Recurrent Hepatitis C After Liver Transplantation with Pegylated Interferon

Background  

The recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) leads to recurrent cirrhosis in up to 40% of patients.     

Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta‐analysis

Aims

To estimate the effects of needle and syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of hepatitis C virus (HCV) in people who inject drugs (PWID).

Methods

Systematic review and meta‐analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within the last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥ 100% coverage (receiving sufficient or greater number of needles and syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non‐randomized studies tool. Random‐effects models were used in meta‐analysis.

Results

We identified 28 studies (n = 6279) in North America (13), United Kingdom (five), Europe (four), Australia (five) and China (one). Studies were at moderate (two), serious (17) critical (seven) and non‐assessable risk of bias (two). Current OST is associated with 50% [risk ratio (RR) =0.50, 95% confidence interval (CI) = 0.40–0.63] reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I² = 0, P = 0.889). Weaker evidence was found for high NSP coverage (RR = 0.79, 95% CI = 0.39–1.61) with high heterogeneity (I² = 77%, P = 0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR = 0.44, 95% CI = 0.24–0.80) with low heterogeneity (I² = 12.3%, P = 0.337), but not in North America (RR = 1.58, I² = 89.5%, P = < 0.001). Combined OST/NSP is associated with a 74% reduction in HCV acquisition risk (RR = 0.26, 95% CI = 0.07–0.89, I² = 80% P = 0.007). According to Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria, the evidence on OST and combined OST/NSP is low quality, while NSP is very low.

Conclusions

Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle and syringe programmes (NSP). There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.     

Human papillomavirus genotype distribution in Madrid and correlation with cytological data

Background

The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period.

Methods

We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up.

Results

Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001].

Conclusion

Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.     

Hepatitis C Virus Clearance in Older Adults

Objectives

To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct‐acting antiviral therapy.

Participants

Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis).

Measurements

We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child‐Pugh‐Turcotte class, Model for End‐Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow‐up were registered.

Results

Ninety‐five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow‐up of 14 ± 4 months (range 5–23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk.

Conclusion

In a real‐world setting, DAAs are safe and effective in older adults with HCV‐related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long‐term DAA therapy.     

An Integrated Alcohol Abuse and Medical Treatment Model for Patients with Hepatitis C

Background  

Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment.     

Diabetes mellitus not an unfavorable factor on the prognosis of hepatitis C virus‐related hepatocellular carcinoma

Aim

Diabetes mellitus (DM) is a potential risk factor for hepatocarcinogenesis, especially in patients with hepatitis C virus (HCV) infection. We aimed to elucidate whether DM influences the surgical outcomes of patients with hepatocellular carcinoma (HCC).

Methods

Our patients were routinely controlled to keep urinary glucose excretion to less than 3.0 g/day before surgery, and the serum glucose level under 200 mg/dL after surgery. The surgical outcomes and postoperative complications of 112 patients with HCV‐related HCC with DM (DM group) were compared to those of 112 propensity‐matched patients without DM (non‐DM group).

Results

After a median follow‐up of 3.2 years (range, 0.2–11.3 years), the median overall (5.2 years; 95% confidence interval, 3.8–6.5 years) and recurrence‐free survival (2.2 years; 1.7–2.9 years) in the DM group were not significantly different from those (6.3 years; 5.4–7.1 years, P = 0.337; and 2.2 years; 1.7–3.6 years, P = 0.613) in the non‐DM group. The independent factors related to overall survival were the background liver (hazard ratio, 2.06; 95% confidence interval, 1.27–3.39, P = 0.014) and tumor differentiation grade (2.07; 1.14–4.05, P = 0.015). Thirty‐two patients (28.5%) in the DM group and 32 patients (28.5%) in the non‐DM group had morbidities after operation, with no significant difference between the groups (P = 1.000). Furthermore, postoperative control status of DM did not affect the prognostic outcome.

Conclusion

Diabetes mellitus does not affect the surgical outcomes of patients with HCV‐related HCC, and it is not an unfavorable factor when selecting candidates for liver resection of HCC.     

Retreatment of hepatitis C patients with pegylated interferon combined with ribavirin in non-responders to interferon plus ribavirin. Is it different in real life?

Background  

More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV.     

Hepatitis C virus prevalence and genetic diversity among pregnant women in Gabon,central Africa

Background  

Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women.     

Risk factors,genotype 6 prevalence,and clinical characteristics of chronic hepatitis C in Southeast Asian Americans

Purpose  

Although infection with hepatitis C virus (HCV) affects 32 million individuals from Southeast Asia, little is known about the mode of HCV acquisition and the epidemiology of chronic hepatitis C (CHC) in these individuals. Our goal was to examine risk factors for HCV acquisition, prevalence, and clinical characteristics of HCV genotype 6 compared with genotypes 1 and 2/3 in Southeast Asian (SEA) patients.     

Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

Background  

Bone marrow suppression is a well-recognized toxicity of the treatment of hepatitis C virus (HCV). Reduction of the peginterferon dose because of neutropenia is common in clinical practice. However, reduction of peginterferon dose during the first weeks of HCV treatment is associated with failure to achieve sustained virological response.