Blood donor screening with cobas s 201/cobas TaqScreen MPX under routine conditions at German Red Cross institutes

Background  In 1997 the German Red Cross (GRC) blood donor services introduced mini-pool nucleic acid testing (NAT) for human immunodeficiency virus (HIV)-1, hepatitis C virus (HCV) and hepatitis B virus (HBV) to increase blood safety. With the new cobas s 201/cobas TaqScreen MPX, a fully automated extraction method and a multiplex amplification system specifically adapted to the needs of blood donation services is available.
Methods  The cobas s 201 system was evaluated at the GRC BTS locations Hagen, Springe and Frankfurt. In phase A, the analytical sensitivity for the detection of HBV, HCV and HIV-1 was investigated and in phase B, at least 60 000 samples at each test site were screened in parallel with the MPX test on s 201 system and the existing routine mini-pool NAT system to compare the diagnostic specificity and the diagnostic sensitivity.
Results  Comparable analytical sensitivities in a range of 1·6–3·6 IU/ml, 4·9–10·9 IU/ml and 14·7–26·6 IU/ml for HBV, HCV HIV, respectively, for the MPX test on s 201 system (95% probability based on probit analysis) were determined at all test sites. The diagnostic sensitivity was 99·8% and the diagnostic specificity was 99·85%.
Conclusions  The MPX test on s 201 system is a fully automated NAT system suitable for routine blood donor screening. The analytical sensitivity as well as the diagnostic sensitivity fulfilled all requirements of the Paul Ehrlich Institute for blood donor screening in mini-pools up to 96 donations per pool. A major benefit of the automated NAT system is the reduced personnel time and the extensive complete barcode-controlled process documentation.     

HIV–HCV co‐infected patients with low CD4+ cell nadirs are at risk for faster fibrosis progression and portal hypertension

Summary. Patients co‐infected with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) are fraught with a rapid fibrosis progression rate and with complications of portal hypertension (PHT) We aimed to assess the influence of immune function [Centers of Disease Control and Prevention (CDC) stage] on development of PHT and disease progression in HIV–HCV co‐infection. Data of 74 interferon‐naïve HIV–HCV co‐infected patients undergoing liver biopsy, measurement of portal pressure and of liver stiffness and routine laboratory tests (including CD4+ cell count, HIV and HCV viral load) were analysed. Time of initial exposure (risk behaviour) was used to assess fibrosis progression. Fibrosis progression, time to cirrhosis and portal pressure were correlated with HIV status (CDC stage). HIV–HCV patients had rapid progression of fibrosis [0.201 ± 0.088 METAVIR fibrosis units/year (FU/y)] and accelerated time to cirrhosis (24 ± 13 years), high HCV viral loads (4.83 × 10⁶ IU/mL) and a mean HVPG at the upper limit of normal (5 mmHg). With moderate or severe immunodeficiency, fibrosis progression was even higher (CDC‐2 = 0.177 FU/y; CDC‐3 = 0.248 FU/y) compared with patients with higher CD4+ nadirs (CDC‐1 = 0.120 FU/y; P = 0.0001). An indirect correlation between CD4+ cell count and rate of fibrosis progression (R = ?0.6654; P < 0.001) could be demonstrated. Hepatic venous pressure gradient (HVPG) showed early elevation of portal pressure with median values of 4, 8 and 12 mmHg after 10, 15 and 20 years of HCV infection for CDC‐3 patients. Patients treated with highly active anti‐retroviral therapy (HAART) had similar rates of progression and portal pressure values than patients without HAART. Progression of HCV disease is accelerated in HIV–HCV co‐infection, being more pronounced in patients with low CD4+ cell count. A history of a CD4+ cell nadir <200/μL is a risk factor for rapid development of cirrhosis and PHT. Thus, HCV treatment should be considered early in patients with HIV–HCV co‐infection and largely preserved CD4+ cell counts.     

Superiority of minipool nucleic acid amplification technology for hepatitis B virus over chemiluminescence immunoassay for hepatitis B surface antigen screening

BACKGROUND AND OBJECTIVES: The Japanese Red Cross (JRC) have developed a fully automated multiplex (MPX) nucleic acid amplification technology (NAT) system for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1). This is used to test serologically negative blood units from volunteer, non-remunerated donors. The system utilizes a 50-sample pool for NAT screening with an input volume of each pool. This results in a significantly higher sensitivity for hepatitis B than that seen with highly sensitive hepatitis B surface antigen (HBsAg) testing. MATERIALS AND METHODS: From 1 February 2000 to 15 October 2001, over 11 million donations, which were serologically negative, were tested using the MPX NAT system. Donations found to be HBV DNA positive were further tested by using the chemiluminescence immunoassay (CLIA). RESULTS: Out of 181 HBV DNA-positive donations, 96 (53%) and 76 (42%) were negative by individual enzyme immunoassay (EIA) and CLIA testing, respectively. CONCLUSIONS: The sensitivity of the 50-sample pool MPX NAT system was higher than that of individual HBsAg screening by CLIA. By adopting this NAT-screening system, the JRC has improved the safety of the blood supply and maintained supply across Japan.     

Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus

Summary. To evaluate, among 70 hepatitis C virus (HCV)‐monoinfected and 36 human immunodeficiency virus (HIV)‐coinfected naïve patients with genotypes 1/4 receiving weight‐adjusted pegylated interferon‐α‐2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV‐RNA decreases. HCV‐RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut‐off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV‐RNA (5·75 vs 5·72 log₁₀IU/ml, P = 0·6), HCV monoinfection led to significantly lower HCV‐RNA values at weeks 4 (3·7 vs 4·3 log₁₀IU/ml, P = 0·01), 12 (2·3 vs 3·5 log₁₀IU/ml, P = 0·01) and 24 (1·4 vs 3·3 log₁₀IU/ml, P = 0·001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0·02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV‐RNA decrease of at least 1 log₁₀ at week 4 was highly predictive of treatment failure for HCV‐monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0·86 [95% confidence interval (CI) 0·77–0·95], but not for HCV/HIV‐coinfected patients (cut‐off, 0 log₁₀, Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0·71 (95% CI 0·49–0·93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1·08–8.04, P = 0·01). Thus the magnitude of HCV‐RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut‐off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.     

GB virus C infection among young,HIV‐negative injection drug users with and without hepatitis C virus infection

Summary. Our study examined the association between GB virus C (GBV‐C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent‐driven methods. Cross‐sectional and longitudinal analyses were completed. GBV‐C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody‐positive (anti‐HCV+) (65.1%) than antibody‐negative (anti‐HCV?) (32.3%) (OR = 3.9, 95% CI: 2.3–6.9) IDUs. The prevalence of resolved GBV‐C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti‐HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV‐C infection. No association between GBV‐C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV‐C infection prevalence was higher among anti‐HCV+ compared to anti‐HCV? young IDUs, similar to prior studies among older populations. In particular, chronically HCV‐infected young IDUs had an increased rate of GBV‐C clearance.     

Chronic hepatitis C infection and liver disease in HIV‐coinfected patients in Asia

Data on markers of hepatitis C virus (HCV) disease in HIV‐HCV‐coinfected patients in resource‐limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan^®) in 480 HIV‐infected patients with positive HCV antibody in four HIV treatment centres in South‐East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7‐42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325‐614) cells/mm³ and 208 (94.1%) of 221 patients tested had HIV‐1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4‐6.6) log₁₀ IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan^®, 143 (37.6%) had no/mild liver fibrosis (F0‐F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan^® failure. In conclusion, a high proportion of HIV‐HCV‐coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).     

The safety of blood donation by elderly blood donors

Background Due to the ageing population, blood donation by the elderly is necessary to maintain blood supply. We initiated a prospective study, to assess whether there is an increased risk of donor reactions in elderly donors. Study Design and Methods In this prospective study, regular donors aged from 66 to 68 and 69 to 71 years were invited to continue blood donation on mobile collection sites of the German Red Cross Blood Service West. A control group (50–52 years) was established. Admission of donors in all groups followed the German national guidelines for blood donation. Donor deferrals and all kinds of donor reactions during donation (on‐site) and in the 48 h following donation (off‐site) were monitored. Results A total of 64 260 valid cases were entered in the study. Donor deferrals increased with age from 1·12% in the control group up to 8·74 in female donors aged 69–71 years. Adverse reactions to blood donation were rare with an overall reaction rate of 0·63% (0·05% on‐site; 0·58% off‐site). Off‐site reactions significantly decreased with increasing age. The relative risk (RR) for adverse reactions in elderly donors compared to the control group (50–52 years) was slightly increased for on‐site reactions in the 69‐ to 71‐year‐old donors (RR 1·0309; 95% CI 1·0292–1·0325). In all other comparisons, the RR for adverse reactions was distinctively lower in elderly donors (RR 0·3785 – 0·7778). Conclusions Our data confirm that elderly regular blood donors may safely continue blood donation at least to the age of 71. Based on these data, we increased the upper age limit.     

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections

Background The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion‐transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Study Design and Methods Post‐transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre‐transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre‐transfusion specimen was non‐reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti‐HBc titres or high anti‐HBc with high anti‐HBs titres. Results Transfusion‐transmitted HCV and HIV infections were not observed. One case of post‐transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451–41 841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty‐four anti‐HBc‐ and/or anti‐HBs‐reactive blood components were transfused to 52 patients non‐reactive for anti‐HBc or anti‐HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). Conclusion This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.     

Correlates of high hepatitis C virus RNA load in a cohort of HIV‐negative and HIV‐positive individuals with haemophilia

Summary. Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV‐RNA load. Correlates of high HCV‐RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV‐infected individuals with haemophilia, we compared those with high (>2 × 10⁶ HCV‐RNA copies/mL) to lower viral load, overall and stratifying on HIV co‐infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P_trend = 0.0001), body mass index ≥25 kg/m² (OR = 1.4, 95% CI = 1.1–1.9), and HIV co‐infection (OR = 1.4, 95% CI = 1.0–1.8). Among 795 HIV‐negative participants, high HCV‐RNA load was associated with older age at HCV acquisition (OR = 1.9 for >15 years vs≤2 years, P_trend = 0.008), and lower AST/platelet ratio (P_trend = 0.01), in addition to longer duration of HCV infection (P_trend = 0.0008), and body mass index ≥25 kg/m² (OR = 1.6, P = 0.005). Among 471 HIV‐positive individuals, anti‐retroviral therapy (ART) was the only variable associated with high HCV‐RNA load (OR = 1.8, CI = 1.1–2.9 for combination ART; OR = 1.8, CI = 0.9–3.4, for other ART vs no treatment). High HCV‐RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end‐stage liver disease.     

Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa‐2a/ribavirin

Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono‐infected and 176 HIV–HCV co‐infected patients treated with peginterferon alfa‐2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono‐infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400 000 IU/mL was used and 16% (59%vs 43%) when 800 000 IU/mL was used. In HIV–HCV genotype 1 co‐infected patients, the difference was 51% (71%vs 20%) when 400 000 IU/mL was used and 43% (61%vs 18%) when 800 000 IU/mL was used. A lower threshold (200 000 IU/mL) was identified for genotype 1 mono‐infected patients with ‘normal’ alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400 000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1‐infected individuals with elevated ALT.     

World Health Organization collaborative study to calibrate the 3rd International Standard for Hepatitis C virus RNA nucleic acid amplification technology (NAT)-based assays

Background and Objectives A collaborative study was undertaken to evaluate a replacement World Health Organization International Standard for hepatitis C virus (HCV) RNA for nucleic acid amplification technology (NAT)‐based assays. The candidate preparations were calibrated in International Units (IUs). Materials and Methods Three new candidate preparations were produced from a single bulk containing anti‐HCV‐negative, genotype 1a HCV RNA–positive plasma. Two samples were lyophilized (coded Sample 2 and Sample 3), whilst a third (Sample 4) contained liquid/frozen material. The samples were distributed together with the 2^nd International Standard (Sample 1, NIBSC code 96/798) for evaluation by thirty‐three laboratories, from fourteen countries. The panel of samples were assayed on four separate occasions. Stability studies were performed for the lyophilized samples by accelerated thermal degradation. Results Participants returned data from a wide range of commercial and in‐house quantitative and qualitative assays. Twenty‐five data sets were returned for quantitative assays and fourteen for qualitative assays. Excellent agreement was observed between laboratories and assay methods. The mean relative potencies of Samples 2–4 were 5·19, 5·41 and 5·70 log₁₀ IU/ml, respectively, when compared against the 2^nd International Standard. Samples 2 and 3 demonstrated stability of a similar order to the previous standards. Conclusions Based upon the results of the collaborative study, Sample 2 (code number 06/100) was established as the 3^rd International Standard for HCV RNA with an assigned unitage of 5·19 log₁₀ IU/ml. Each vial contains the equivalent of 0·5 ml of material; each vial contains 4·89 log₁₀ IU of HCV RNA.     

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.     

Multicenter Study of Pegylated Interferon α‐2a Monotherapy for Hepatitis C Virus‐Infected Patients on Hemodialysis: REACH Study

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)‐infected dialysis patients. The rate of HCV‐infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α‐2a (PEG‐IFNα‐2a) monotherapy in HCV‐infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 μg PEG‐IFNα‐2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 μg PEG‐IFNα‐2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG‐IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.     

Payment for whole blood donations in Lithuania: the risk for infectious disease markers

Background and Objectives In Lithuania, remuneration for whole blood donations still prevails, with the government covering payment for the donors. The payment per donation in cash is equal to 40 litas (€11·6); it is offered to all blood donors and accepted by the majority of them. Donors who gave blood and received the payment are treated as remunerated donors; those who gave blood and did not take the payment are treated as non‐remunerated ones. The purpose of this study was to assess the risk of payment for whole blood donations and to analyse the prevalence of infectious diseases markers per 100 remunerated and non‐remunerated, first‐time and regular whole blood donations, and to compare the risk ratios of infectious disease markers of remunerated and non‐remunerated whole blood donations in 2005 and 2006 at the National Blood Center in Lithuania. Materials and Methods Whole blood donors were categorized as follows: (i) first‐time donor, remunerated; (ii) first‐time donor, non‐remunerated; (iii) regular donor, remunerated; and (iv) regular donor, non‐remunerated. The blood donations were analysed for the presence or absence of the following infectious disease markers: anti‐hepatitis C virus (anti‐HCV), hepatitis B surface antigen (HBsAg), anti‐human immunodeficiency virus (anti‐HIV ¹/₂) and syphilis. Only confirmed infectious disease markers were classified. To assess the risk of payment for whole blood donations, the prevalence of infectious disease markers per 100 donations in the different donor groups and the risk ratios between the remunerated and non‐remunerated donations were determined. Results The prevalence per 100 first‐time remunerated donations was: for anti‐HCV 1·84 (2005) and 2·98 (2006); for HBsAg 1·73 (2005) and 2·03 (2006); for syphilis 0·67 (2005) and 1·03 (2006). The prevalence per 100 first‐time non‐remunerated donations was: for anti‐HCV 0·93 (2005) and 0·98 (2006); for HBsAg 1·57 (2005) and 1·33 (2006); for syphilis 0·29 (2005) and 0·47 (2006). The first‐time donors who were remunerated for whole blood donations had a significantly higher prevalence of infectious disease markers per 100 donations and a higher risk ratio for at least three infectious disease markers (HBsAg, anti‐HCV and syphilis) as compared to first‐time donors who were non‐remunerated. The regular donors who were non‐remunerated for whole blood donations had the lowest prevalence of all infectious disease markers: anti‐HCV –0·03 (2005) and 0·04 (2005); syphilis –0·06 (2005) and 0·02 (2006); and any positive cases of HBsAg and anti‐HIV ¹/₂ were found both in 2005 and 2006. No statistically significance differences in incidence and risk ratio existed when comparing the regular donations who were remunerated and non‐remunerated. Conclusion The payment for whole blood donors provides a higher risk for infectious disease markers of first‐time donations at the National Blood Center in Lithuania.     

Risk of hepatitis B virus reactivation in hepatitis B virus + hepatitis C virus‐co‐infected patients with compensated liver cirrhosis treated with ombitasvir,paritaprevir/r + dasabuvir + ribavirin

Hepatitis B virus may reactivate in patients with chronic hepatitis C treated with direct‐acting antivirals. The aim of this study was to investigate the risk of hepatitis B virus (HBV) reactivation in HBV + hepatitis C virus (HCV)‐co‐infected patients with compensated liver cirrhosis treated with paritaprevir/ombitasvir/ritonavir, dasabuvir with ribavirin. We reviewed prospectively gathered data from a national cohort of 2070 hepatitis C virus patients with compensated liver cirrhosis who received reimbursed paritaprevir/ombitasvir/r, dasabuvir with ribavirin for 12 weeks from the Romanian National Health Agency during 2015‐2016. Twenty‐five patients in this cohort were HBs antigen positive (1.2%); 15 untreated with nucleotide analogues agreed to enter the study. These patients were followed up: ALT monthly, serology for HBV and DNA viral load at baseline, EOT and SVR at 12 weeks. Hepatitis B virus (HBV)‐co‐infected patients were all genotype 1b and 52% females, with a median age of 60 years (51 ÷ 74); 76% were pretreated with peginterferon + ribavirin; 72% were with severe necroinflammatory activity on FibroMax assessment; 40% presented comorbidities; and all were HBe antigen negative. Hepatitis C virus (HCV) SVR response rate was 100%. Hepatitis B virus (HBV)‐DNA viral load was undetectable in 7/15 (47%) before therapy, and for the other 8 patients, it varied between below 20 and 867 IU/mL. Five patients (33%) presented virological reactivation (>2 log increase in HBV‐DNA levels) during therapy. One patient presented with hepatitis associated with HBV reactivation, and two started anti‐HBV therapy with entecavir. Hepatitis B virus (HBV) virological reactivation was present in 33% in our patients. Generally, HBV‐DNA elevations were mild (<20 000 IU/mL); however, we report one case of hepatitis associated with HBV reactivation.     

Coinfection with hepatitis C virus,oxidative stress and antioxidant status in HIV‐positive drug users in Miami*

Background

The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV‐coinfected and HIV‐monoinfected adults.

Methods

Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB‐4) markers were calculated.

Results

Significant differences were found between HIV/HCV‐coinfected and HIV‐monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P<0.001), APRI (0.52±0.37 vs. 0.255±0.145; P=0.0001), FIB‐4 (1.64±.0.91 vs. 1.03±0.11; P=0.0015) and plasma albumin (3.74±0.65 vs. 3.94±0.52 g/dL; P=0.038). There were no significant differences in CD4 cell count, HIV viral load or antiretroviral therapy (ART) between groups. Mean MDA was significantly higher (1.897±0.835 vs. 1.344± 0.223 nmol/mL, respectively; P=0.006) and plasma antioxidant concentrations were significantly lower [vitamin A, 39.5 ± 14.1 vs. 52.4±16.2 μg/dL, respectively (P=0.0004); vitamin E, 8.29±2.1 vs. 9.89±4.5 μg/mL (P=0.043); zinc, 0.61±0.14 vs. 0.67±0.15 mg/L (P=0.016)] in the HIV/HCV‐coinfected participants than in the HIV‐monoinfected participants, and these differences remained significant after adjusting for age, gender, CD4 cell count, HIV viral load, injecting drug use and race. There were no significant differences in glutathione peroxidase concentration, selenium concentration, body mass index (BMI), alcohol use or tobacco use between groups. Glutathione peroxidase concentration significantly increased as liver disease advanced, as measured by APRI (β=0.00118; P=0.0082) and FIB‐4 (β=0.0029; P=0.0177). Vitamin A concentration significantly decreased (β=?0.00581; P=0.0417) as APRI increased.

Conclusion

HIV/HCV coinfection is associated with increased oxidative stress and decreased plasma antioxidant concentrations compared with HIV monoinfection. Research is needed to determine whether antioxidant supplementation delays liver disease in HIV/HCV coinfection.

     

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV‐co‐infected patients with mild liver disease

New direct‐acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult‐to‐treat, including those HIV/HCV co‐infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co‐infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV‐co‐infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty‐three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5000 per‐patient) compared to (£10 775 per‐patient) non‐SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co‐infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.     

Peginterferon α‐2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single‐centre study of 367 cases

Background/aims: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti‐HCV thrapy but there is little information about safety and efficacy of peginterferon α‐2a and ribavirin combination therapy in these patients. Material and methods: In an open‐label single‐treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 μg of Pegasys^® and 800–1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Results: Two hundred and twenty‐five subjects [61%, 95% confidence interval (CI) 56–66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1–3.1), genotype non‐1 OR=1.8 (95% CI 1.1–3.2), BMI<25 OR=2.1 (95% CI 1.3–3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1–3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow‐up after treatment cessation. Conclusions: Peginterferon alpha‐2a in combination with weight‐based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non‐1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non‐1 are the major determinants of SVR achievement in these patients.     

HIV‐positive men who have sex with men are at high risk of development of significant liver fibrosis after an episode of acute hepatitis C

Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)‐infected men who have sex with men (MSM). New direct‐acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single‐centre cohort of HIV‐positive MSM with acute HCV infection. Liver fibrosis was estimated by Fibroscan^® and Fibrotest^®. Liver‐related and non‐liver‐related outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men were documented. Median follow‐up for all included patients was 38.7 months. Spontaneous HCV clearance was found in 10.8% of patients, which was significantly associated with older age, lower HCV RNA levels, and higher ALT levels upon initial acute HCV diagnosis. Treatment with interferon‐based therapy was initiated in 86.3% of cases, resulting in a sustained virological response(SVR) rate of 70.7%. After 3 years’ follow‐up, significant liver fibrosis of METAVIR F2 stage or higher was found in 39.4% of patients after first acute HCV diagnosis. Higher age, physician‐declared alcoholism, and nonresponse to acute HCV therapy were independently associated with higher fibrosis stages. Ten patients died during the observation period (IR 1.4/100 patient‐years) and four during interferon treatment. Significant liver fibrosis is a common finding in HIV‐positive MSM following acute HCV infection despite high treatment uptake and cure rates, suggesting the need for close liver disease monitoring particularly if HCV treatment is deferred.