Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis.

BACKGROUND AND AIMS: The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS: This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS: The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION: The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.

Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation.

INTRODUCTION: Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. AIM: To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). PATIENTS AND METHODS: Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. RESULTS: Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50-64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1-5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p=0.047) and 20.58 (p=0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k=0.033). DISCUSSION: Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.

Risks of hepatocellular carcinoma and cirrhosis-associated complications in patients with rheumatoid arthritis: a 10-year population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: Although rheumatoid arthritis (RA) has been linked to several important malignancies, data for the risks of hepatocellular carcinoma (HCC) in patients with RA are scarce. We aimed to examine the risk of HCC and cirrhosis-associated complications and the use of biologics in a national representative RA sample in Taiwan. METHODS: All study subjects aged ≥ 18 years in the Taiwan National Health Insurance program between January 1, 2000, and December 31, 2009 were enrolled. We matched RA and non-RA subjects by propensity scores in a 1:1 ratio. Our primary outcome was a diagnosis of HCC and cirrhosis-associated complications during a 10-year follow-up period. The risk of outcomes was represented as a hazard ratio (HR) calculated in Cox proportional hazard regression models. RESULTS: 24,245 RA and 24,245 non-RA subjects were included in the primary outcome analysis. Mean overall person-years (PY) of follow-up were 116,608 PY for the RA cohort, and 234,280 PY for the non-RA cohort. The overall incidence of HCC and cirrhosis-associated complications was lower in the RA cohort than in the non-RA cohort (0.66% vs. 1.41% HCC events and 1.45% vs. 1.95% cirrhosis-associated complications events during 10-year follow-up). The HRs adjusted for age, sex, the frequency of medical visits, and CCI were 0.57 (0.46-0.71) for HCC and 0.67 (0.59-0.76) for HCC and cirrhosis-associated complications. Although immunomodulatory agents may alter the risk of malignancy, use of biologics did not increase HCC risk in RA patients. CONCLUSIONS: RA is associated with a reduced risk of developing HCC and cirrhosis-associated complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02880306.

Incidentally detected asymptomatic hepatitis C virus infection with significant fibrosis: Possible impacts on management.

BACKGROUND AND AIMS: Liver biopsy may be considered in patients with hepatitis C virus (HCV) infection to assess the severity of liver injury and stage of fibrosis, thereby guiding therapeutic decisions. In addition, advanced stage also necessitates surveillance for hepatocellular carcinoma. The aim of this study was to assess whether transaminase (alanine transaminase [ALT]) levels and RNA titers correlate with the histological activity index (HAI) and fibrosis (F) stage in asymptomatic patients with incidentally detected HCV (IDHCV). PATIENTS AND METHODS: Retrospective evaluation of liver biopsies was done in 113 patients with IDHCV, diagnosed during routine screening. Decision of liver biopsy was made on the basis of age, genotype, acceptable clinical, hematological, and biochemical profiles, and willingness of the patients to undergo treatment. Serum ALT levels, HCV RNA titers, and genotypes were correlated with HAI and F stage. RESULTS: Genotyping was done in 77 of the 113 patients, of which genotype 3 was seen in 43 and genotype 1 in 25 patients. A higher fibrosis stage (Ishak's >F2) was noted in 23.8% of the biopsies. Serum ALT showed a significant correlation with the HAI score on liver biopsy (P = 0.01) but not with the stage of fibrosis (P = 0.52). HCV RNA titers did not reveal any correlation with HAI score or fibrosis stage. CONCLUSION: Serum transaminases and HCV RNA titers are poor predictors of disease severity and fibrosis. Since HCV shows a slow disease progression, higher stage may predict a worse prognosis irrespective of the low viral RNA load. Liver biopsy may help guide therapeutic decisions in IDHCV infection.

Benefit-risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation.

On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination (FDC), an interferon-free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing a nonstructural protein 5A (NS5A) inhibitor; and • genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. Approval was based on an acceptable safety profile and high sustained virological response rates 12 weeks after the end of treatment (SVR12) in two phase 3 clinical trials in subjects previously treated with a direct-acting antiviral (DAA) regimen. In POLARIS-1, 96% of SOF/VEL/VOX-treated subjects achieved SVR12. In POLARIS-4, 98% of SOF/VEL/VOX-treated subjects achieved SVR12. A key and challenging question in evaluating the data was determining the contribution of VOX to SOF/VEL and how this differed depending on the genotype and patient population. In this article, we provide our perspective on the issues considered in making these determinations, especially regarding the POLARIS-4 data in subjects who have previously been treated with a chronic HCV regimen containing sofosbuvir without an NS5A inhibitor. Conclusion: We seek to provide context as to why a broad indication was given for NS5A inhibitor-experienced patients (HCV genotypes 1-6) while the indication for NS5A inhibitor- naïve patients was limited to HCV genotypes 1a and 3 only. (Hepatology 2018;67:482-491).

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

Ultra-Deep Sequencing Characterization of HCV Samples with Equivocal Typing Results Determined with a Commercial Assay.

Hepatitis C virus (HCV) is classified into seven phylogenetically distinct genotypes, which are further subdivided into related subtypes. Accurate assignment of genotype/subtype is mandatory in the era of directly acting antivirals. Several molecular methods are available for HCV genotyping; however, a relevant number of samples with indeterminate, mixed, or unspecified subtype results, or even with misclassified genotypes, may occur. Using NS5B direct (DS) and ultra-deep pyrosequencing (UDPS), we have tested 43 samples, which resulted in genotype 1 unsubtyped (n = 17), mixed infection (n = 17), or indeterminate (n = 9) with the Abbott RealTime HCV Genotype II assay. Genotype 1 was confirmed in 14/17 samples (82%): eight resulted in subtype 1b, and five resulted in subtype 1a with both DS and UDPS, while one was classified as subtype 1e by DS and mixed infection (1e + 1a) by UDPS. Three of seventeen genotype 1 samples resulted in genotype 3h with both sequencing approaches. Only one mixed infection was confirmed by UDPS (4d + 1a), while in 88% of cases a single component of the mixture was detected (five genotype 1a, four genotype 1b, two genotype 3a, two genotype 4m, and two genotype 4d); 44% of indeterminate samples resulted genotype 2c by both DS and UDPS, 22% resulted genotype 3a; one indeterminate sample by Abbott resulted in genotype 4d, one resulted in genotype 6n, and one was classified as subtype 3a by DS, and resulted mixed infection (3a + 3h) by UDPS. The concordance between DS and UDPS was 94%, 88%, and 89% for genotype 1, co-infection, and indeterminate results, respectively. UDPS should be considered very useful to resolve ambiguous HCV genotyping results.

Epidemic History of Hepatitis C Virus among Patients with Inherited Bleeding Disorders in Iran.

The high rate of hepatitis C virus (HCV) infection among transfusion related risk groups such as patients with inherited bleeding disorders highlighting the investigation on prevalent subtypes and their epidemic history among this group. In this study, 166 new HCV NS5B sequences isolated from patients with inherited bleeding disorders together with 29 sequences related to hemophiliacs obtained from a previous study on diversity of HCV in Iran were analyzed. The most prevalent subtype was 1a (65%), followed by 3a (18.7%),1b (14.5%),4(1.2%) and 2k (0.6%). Subtypes 1a and 3a showed exponential expansion during the 20th century. Whereas expansion of 3a started around 20 years earlier than 1a among the study patients, the epidemic growth of 1a revealed a delay of about 10 years compared with that found for this subtype in developed countries. Our results supported the view that the spread of 3a reached the plateau 10 years prior to the screening of blood donors for HCV. Rather, 1a reached the plateau when screening program was implemented. The differences observed in the epidemic behavior of HCV-1a and 3a may be associated with different transmission routes of two subtypes. Indeed, expansion of 1a was more commonly linked to blood transfusion, while 3a was more strongly associated to drug use and specially IDU after 1960. Our findings also showed HCV transmission through blood products has effectively been controlled from late 1990s. In conclusion, the implementation of strategies such as standard surveillance programs and subsiding antiviral treatments seems to be essential to both prevent new HCV infections and to decline the current and future HCV disease among Iranian patients with inherited bleeding disorders.

On-site bundled rapid HIV/HCV testing in substance use disorder treatment programs: study protocol for a hybrid design randomized controlled trial.

BACKGROUND: More than 1.2 million people in the United States are living with human immunodeficiency virus (HIV), and 3.2 million are living with hepatitis C virus (HCV). An estimated 25 % of persons living with HIV also have HCV. It is therefore of great public health importance to ensure the prompt diagnosis of both HIV and HCV in populations that have the highest prevalence of both infections, including individuals with substance use disorders (SUD). METHODS/DESIGN: In this theory-driven, efficacy-effectiveness-implementation hybrid study, we will develop and test an on-site bundled rapid HIV/HCV testing intervention for SUD treatment programs. Its aim is to increase the receipt of HIV and HCV test results among SUD treatment patients. Using a rigorous process involving patients, providers, and program managers, we will incorporate rapid HCV testing into evidence-based HIV testing and linkage to care interventions. We will then test, in a randomized controlled trial, the extent to which this bundled rapid HIV/HCV testing approach increases receipt of HIV and HCV test results. Lastly, we will conduct formative research to understand the barriers to, and facilitators of, the adoption, implementation, and sustainability of the bundled rapid testing strategy in SUD treatment programs. DISCUSSION: Novel approaches that effectively integrate on-site rapid HIV and rapid HCV testing are needed to address both the HIV and HCV epidemics. If feasible and efficacious, bundled rapid HIV/HCV testing may offer a scalable, potentially cost-effective approach to testing high-risk populations, such as patients of SUD treatment programs. It may ultimately lead to improved linkage to care and progress through the HIV and HCV care and treatment cascades. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02355080 . (30 January 2015).

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis

BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCVRNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

BACKGROUND/AIMS: Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. METHODS: Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. RESULTS: Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. CONCLUSION: This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype.

The Hepatitis Aggressiveness Score (HAS): a novel classification system for post-liver transplantation recurrent hepatitis C.

Several histopathologic features have been described in cases of fibrosing cholestatic hepatitis C (FCH-C). We investigated whether FCH-associated features can be utilized as the basis of a novel grading system for the entire population of post-liver transplantation (LT) recurrent hepatitis C virus (HCV) infection. Liver biopsies obtained at a median (interquartile range) of 12.3 (10.4-13.8) months post-LT from 170 patients with recurrent HCV were included. Biopsies were assessed for the following FCH features: (1) ductular reaction, (2) cholestasis, (3) hepatocyte ballooning, and (4) periportal sinusoidal fibrosis. A Hepatitis Aggressiveness Score (HAS) was assigned on the basis of the number of FCH features as follows: 0 features=HAS 1; 1 to 2 features=HAS 2; and 3 to 4 features=HAS 3. We analyzed the performance of this novel system in predicting clinicopathologic outcomes compared with conventional grading systems after a median (interquartile range) follow-up of 24 (13-45.5) months. The HAS classification was highly predictive of fibrosis progression (P<0.001) and was the best predictor of graft loss in a multivariable analysis model, which included all conventional hepatitis grading systems (adjusted hazard ratio=5.5, confidence interval 2.9-10.7, P<0.001 for HAS 3 vs. HAS 1 and 2, compared with adjusted hazard ratio=1.0, confidence interval 0.5-1.9, P=0.94 for the presence of moderate to severe necroinflammation by at least 1 conventional grading system). Presence of at least 3 of 4 FCH features (HAS 3 group) characterized a subset of patients with distinctly worse prognosis and severe cholestatic disease (ie, FCH-C). We propose a novel approach to the histologic grading of post-LT recurrent HCV based exclusively on FCH features. This system allows accurate identification of FCH-C cases and stratification of all recurrent HCV patients into distinct prognostic categories.

Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

BACKGROUND/AIMS: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. METHODOLOGY: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 µg and 90 µg groups, and were 48 or 24 weeks in the 180 µg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. RESULTS: There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. CONCLUSIONS: Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.

Hepatitis C in prisoners and non-prisoners in Colatina, Espírito Santo, Brazil

The aim of the present work was to compare hepatitis C prevalence, genotypes, and risk factors between prisoners and non-prisoners in the city of Colatina, Espírito Santo, Brazil. This cross-sectional study involved approximately 1,600 residents and 730 prisoners, all of whom were living in Colatina. The percentage of individuals who tested positive for anti-HCV was 0.1% (2/1,600) in the non-prisoner group and 1.0% (7/730) in the prisoner group, confirming a higher risk of hepatitis C in the latter group. The percentage of subjects who progressed to HCV-RNA negative was 11.1% (1/9), confirming the high probability of evolution to chronicity. Genotype 1 was the most predominant genotype found. Factors associated with increased risk of hepatitis C were being male, being institutionalized, having an income of less than three minimum wages, having low educational attainment, and using injected drugs. Alcohol use, pain in the liver, migraine, and reported history of hepatitis were markedly associated with hepatitis C. The prison population tested positive for anti-HCV at a higher rate than the non-prison population.

O objetivo do presente trabalho foi comparar a prevalência, os genótipos e fatores de risco da hepatite C entre a população em geral e os presos na cidade de Colatina, Espírito Santo, Brasil. O presente estudo é transversal e comparou cerca de 1.600 moradores e 730 prisioneiros, todos eles vivendo em Colatina. A prevalência de anticorpos anti-HCV positivo foi de 0,1% (2/1.600), na população em geral, e de 1,0% (7/730) entre os presos, o que confirma o elevado risco nesse grupo. A percentagem de indivíduos que apresentam RNA-HCV negativo foi de 11,1% (1/9), confirmando a alta taxa de evolução para a cronicidade. O genótipo predominante foi o I. Fatores associados ao aumento do risco de hepatite C foram do sexo masculino, sendo institucionalizado, com renda de até três salários mínimos, baixa escolaridade e uso de drogas injetáveis. O uso de álcool, dor no fígado, enxaqueca e relato de histórias de hepatite apresentaram associação significativa com a hepatite C. A população carcerária teve maiores taxas de positividade para o anti-HCV do que a população não-prisional pesquisada.

Hepatitis C virus network based classification of hepatocellular cirrhosis and carcinoma.

Hepatitis C virus (HCV) is a main risk factor for liver cirrhosis and hepatocellular carcinoma, particularly to those patients with chronic liver disease or injury. The similar etiology leads to a high correlation of the patients suffering from the disease of liver cirrhosis with those suffering from the disease of hepatocellular carcinoma. However, the biological mechanism for the relationship between these two kinds of diseases is not clear. The present study was initiated in an attempt to investigate into the HCV infection protein network, in hopes to find good biomarkers for diagnosing the two diseases as well as gain insights into their progression mechanisms. To realize this, two potential biomarker pools were defined: (i) the target genes of HCV, and (ii) the between genes on the shortest paths among the target genes of HCV. Meanwhile, a predictor was developed for identifying the liver tissue samples among the following three categories: (i) normal, (ii) cirrhosis, and (iii) hepatocellular carcinoma. Interestingly, it was observed that the identification accuracy was higher with the tissue samples defined by extracting the features from the second biomarker pool than that with the samples defined based on the first biomarker pool. The identification accuracy by the jackknife validation for the between-genes approach was 0.960, indicating that the novel approach holds a quite promising potential in helping find effective biomarkers for diagnosing the liver cirrhosis disease and the hepatocellular carcinoma disease. It may also provide useful insights for in-depth study of the biological mechanisms of HCV-induced cirrhosis and hepatocellular carcinoma.

Latent classes of heroin and cocaine users predict unique HIV/HCV risk factors.

BACKGROUND: Patterns of heroin and cocaine use vary and may be associated with unique risk factors for bloodborne infections. METHODS: Latent class analysis identified sub-populations of 552 heroin and cocaine users in Baltimore, Maryland. Using latent class regression, these classes were analyzed for associations with demographic characteristics, risky behaviors, Hepatitis C, and HIV. RESULTS: Three classes were found: Crack/Nasal-Heroin users (43.5%), Polysubstance users (34.8%), and Heroin Injectors (21.8%). Compared to Polysubstance users, Crack/Nasal-Heroin users were almost 7 times more likely to identify as Black (OR=6.97, 95% CI=4.35-11.2). Sharing needles was over 2.5 times more likely among Polysubstance users than among Heroin Injectors (OR=2.66, 95% CI=1.49-4.75). Crack/Nasal-Heroin users were 2.5 times more likely than Polysubstance users to exchange drugs for sex (OR=2.50, 95% CI=1.22-5.13). Crack/Nasal-Heroin users were less likely than Heroin Injectors to have Hepatitis C (OR=0.10, 95% CI=0.06-0.18), but no significant differences were found for HIV. CONCLUSIONS: Subpopulations of cocaine and heroin users differed in demographic classifications, HIV-risk behaviors, and Hepatitis C infection. All subpopulations included substantial numbers of HIV-positive individuals. Findings provide further evidence that non-injection drug users face significant infectious disease risk.

[Studies on HCV infection prevalence in Poland--where are we?]. / Badania rozpowszechnienia HCV w Polsce--gdzie jestesmy?

Numerous studies conducted in HCV infection over the past several years in Poland have focused on clinical course, treatment and epidemiology in selected high risk groups. Studies estimating the prevalence of HCV in the current general population are lacking. Various studies conducted in subpopulations yielding values ranging from 0.9% to over 4%. In the present paper we attempt to explain these discrepancies and assess the reliability of available data. We included prevalence studies published in 2000-2009, which could refer to the general adult population in Poland. All available studies in terms of possible conclusion about the general population suffered from systematic errors, most commonly selection bias (e.g., volunteer bias, hospital bias), or misclassification (no confirmation of detected anti-HCV). Given estimates often referred only to selected regions or age groups. Extrapolating these results to estimate the burden of illness in general population may lead to incorrect assessment, thus currently there is no scientific basis for planning screening programs and national strategies against HCV.

Frequent multiple hepatitis C virus infections among injection drug users in a prison setting.

UNLABELLED: Recent data indicate that multiple hepatitis C virus (HCV) infections (mixed infection, superinfection, and reinfection) are common among injection drug users (IDUs). In this study, we identified and characterized multiple HCV infection episodes among HCV-seronegative IDU prison inmates (n = 488) enrolled in the Hepatitis C Incidence and Transmission Study cohort. Incident HCV infection with detectable HCV RNA was identified in 87 subjects, 48 of whom completed additional follow-up to screen for reinfection or superinfection. All HCV RNA-detectable samples were tested for multiple infection through a series of specifically designed nested reverse-transcription polymerase chain reaction (nRT-PCR) with sequencing and HCV RNA level measurement. Sequencing revealed that 22 of 87 (25.3%) subjects were infected by two or more viruses. Nine (10.3%) subjects were designated as prevalent cases of incident mixed infection, because two distinct HCV strains were detected at the first viremic time point. Fifteen further cases of multiple HCV infection (superinfection or reinfection) were identified, two of which also showed baseline incident mixed infections. The incidence of new HCV infection (superinfection and reinfection) during follow-up was 40/100 person-years (95% confidence interval, 33-44/100 person-years). Spontaneous clearance of viruses from one subtype and persistence of the other subtype after mixed infection was observed in eight subjects. In these subjects, the virus with higher HCV RNA levels superseded the other. CONCLUSION: This study comprehensively analyzed frequent multiple HCV infections in a high-risk cohort and provides further insight into infection dynamics and immunity after exposure to variant viral strains. The data presented suggest that HCV RNA levels play an important role in viral competition.