Hepatitis C Virus RNA Polymerase Chain Reaction Research Articles

Rome IV Diagnostic Criteria for Functional Gastrointestinal Disorders in Patients with Chronic Hepatitis C Virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) usually have different abdominal complaints without any organic lesions. The functional cause of these complaints is claimed in most patients. This study aimed to evaluate functional gastrointestinal disorders (FGIDs) in patients with chronic hepatitis C using Rome IV diagnostic criteria. METHODS: This study included 1506 participants (1006 patients with chronic HCV, and 500 controls). All individuals were subjected to taking thorough medical history, basic investigations (complete blood counts, liver and renal functions tests), international normalized ratio (INR), alpha-fetoprotein, HCV RNA PCR (polymerase chain reaction), abdominal ultrasonography, and upper gastrointestinal tract (GIT) endoscopy for patients only), and Rome IV diagnostic questionnaire. RESULTS: Patients with HCV had symptoms of FGIDs including functional dyspepsia (FD) (P=0.009), early satiety (P=0.002), postprandial distress (P=0.02), epigastric pain (P=0.03), Inflammatory bowel syndrome (IBS) (P<0.001), IBS predominant constipation (P<0.001), IBS predominant diarrhea (P<0.001), and IBS mixed (P<0.001). There were multiple factors for the prediction of FD in patients with HCV, including high body mass index (BMI), education level, positive polymerase chain reaction (PCR), and fibrosis stage. Also, there were multiple factors for the prediction of IBS in patients with HCV, including male gender, high BMI, urban residence, education level, positive PCR, and fibrosis stage. CONCLUSIONS: FD is a prevalent finding in obese patients with HCV and with higher fibrosis scores. IBS is also prevalent in male patients with HCV.

Study of the Effectiveness of Ledipasvir/Sofosbuvir Treatment Regimen in Patients with Chronic Hepatitis C Virus (HCV) Infection

Abstract Background: Treatment of Hepatitis C Virus (HCV) infection had significantly changed during the last few years. The combination of Sofosbuvir and Ledipasvir (SOF/LDV) has been shown to treat high proportions of patients with HCV. Aim of Study: The aim of the work was to assess the efficacy and risk factors for failure of SOF/LDV in Egyptian patients with HCV infection. Patients and Methods: In this prospective study, 138 patients who were HCV antibody positive and HCV RNA positive by Polymerase Chain Reaction (PCR), aged between 18 and 75 years, were enrolled. The patients assessed demo-graphically, and by laboratory and ultrasound. The patients received daily Sofosbuvir 400mg plus Ledipasvir 90mg for 12 weeks, the primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative PCR for HCV RNA. The patients were classified into two groups according to SVR12: Respond-ers included 133 patients who had undetectable level of HCV RNA and non-responders included 5 patients who had detect-able level of HCV RNA. Results: The overall SVR12 was 96.4%. The response of cirrhotic vs. non-cirrhotic patients was (80% vs. 98.4) with statistically significant p-value (p<0.05) with specificity 90% and sensitivity 60% (odds ratio=15.125, 95% confidence interval 2.29-99.6, p<0.05), and the response of naive vs. experienced patients was (97.6% vs. 83.3%) with statistically significant p-value (p<0.05) with specificity 92.5% and sensitivity 40% (odds ratio=8.2, 95% confidence interval 1.22-54.9, p<0.05). Conclusion: Sofosbuvir/Ledipasvir combination for 12 weeks was very effective for chronic HCV treatment, cirrhosis and treatment-experienced patients were associated with decreased likelihood of SVR.

PB1832 MATRIX CHEMOTHERAPY FOR PRIMARY CNS LYMHPOMA COMPLICATED WITH HCV INFECTION AND SUCCESSFUL ERADICATION OF BOTH DISEASES

Background:There is a well‐known connection between Hepatitis C virus (HCV) infection and B‐cell lymphomas (BCL). HCV infected patients have an increased risk of developing BCL. Hypothetically, lymphomagenesis can be induced by chronic antigen stimulation (analogous to Helicobacter pylori associated gastric marginal zone lymphoma) and/or a direct pro‐oncogenic effect of intracellular HCV proteins. Several studies have demonstrated that antiviral therapy may induce remission and improve prognosis of HCV‐associated lymphomas. On the other hand, HCV infection can cause sever complication during the immunochemotherapy and stem cell transplantation. These patients are at risk for HCV reactivation, accelerated liver disease progression, drug‐induced liver toxicity. Thus, HCV‐infected patients often suffer treatment delays, reduced dose intensity, and many times are excluded from bone marrow transplantation. Accordingly, there is some evidence of negative prognostic impact of HCV infection on survival.Aims:To draw attention to the HCV caused complications during lymphoma treatment.Methods:Here we present the case of a HCV‐infected patient with primary central nervous system (CNS) lymphoma complicated with HCV infection and review the relevant literature.Results:A 56‐year old woman with CNS lymphoma was treated with MATRIX (methotrexate, cytarabine, thiotepa, and rituximab). Initial serum serology showed reactivity to HBcAg and HCV. Polymerase chain reaction (PCR) detected no hepatits B virus DNA, however the copy number for hepatitis C virus (HCV) RNA was 104 850 000 IU/ml. She received HBV prophylaxis with lamivudine and subsequently entecavir against reactivation of HBV. After the 2nd cycle of chemotherapy her liver function tests became severely abnormal (AST: 514 U/L ALT: 264 U/L, ALP: 145 U/L, GGT: 1328 U/L, total Bi: 74.6 umol/L, conjugated Bi: 63.5 umol/L). The patient was asymptomatic regarding the lymphoma and in complete remission according to MRI scans. Further systemic chemotherapy had to be halted. The HBV DNA was still undetectable by PCR. Drug induced or mechanical cholestasis and the role of ongoing HCV infection was contemplated. The biliary tracts were not dilated on ultrasound scans. She had an ERCP with sphincterotomy and sofosbuvir plus ledipasvir plus ribavirin treatment for HCV was started. Meanwhile, intrathecal methotrexate therapy was administered 3‐weekly to bridge till next chemotherapy. The antiviral therapy was completed without any side effects and at 3 months, her HCV RNA PCR was negative with entirely normal liver function. The patient achieved sustained virological response. Two more cycles of MATRIX was delivered and an autologous stem cell transplantation with BCNU and thiothepa conditioning. Liver function remained normal ever since.Summary/Conclusion:This is a rare case where the role of HCV infection in liver damage during systemic chemotherapy is highly possible. We would like to draw attention to the liver vulnerability caused by chronic HCV infection. Nowadays HCV eradication is feasible with novel direct acting antiviral therapies, HCV‐infection should not contraindicate the adequate chemotherapy.

Cluster of differentiation 4+ T-cell counts and human immunodeficiency virus-1 viral load in patients coinfected with hepatitis B virus and hepatitis C virus.

BACKGROUND:Coinfections of human immunodeficiency virus (HIV) with hepatitis viruses may affect the progress of disease and response to therapy.OBJECTIVES:To study the incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfections in HIV-positive patients and their influence on HIV-1 viral load and cluster of differentiation 4+ (CD4+) T-cell counts.MATERIALS AND METHODS:This pilot study was done on 179 HIV-positive patients attending antiretroviral therapy (ART) centre. Their blood samples were tested for HIV-1 viral load, CD4+ T-cell counts, hepatitis B surface antigen, anti-HCV antibodies, HBV DNA and HCV RNA polymerase chain reaction.RESULTS:Among the 179 patients, 7.82% (14/179) were coinfected with HBV and 4.46% (8/179) with HCV. Median CD4+ T-cell count of HIV monoinfected patients was 200 cells/μl and viral load was 1.67 log10 copies/μl. Median CD4+ T-cell counts of 193 cells/μl for HBV (P = 0.230) and 197 cells/μl for HCV (P = 0.610) coinfected patients were similar to that of HIV monoinfected patients. Viral load was higher in both HBV and HCV infected patients but statistically significant only for HCV (P = 0.017). Increase in CD4+ T-cell counts and decrease in HIV-1 viral load in coinfected patients on 2 years of ART were lower than that in HIV monoinfected patients.CONCLUSION:HBV/HCV coinfected HIV patients had similar CD4+ T-cell counts as in HIV monoinfected patients, higher HIV viral load both in chemo-naive patients and in those on ART as compared to HIV monoinfected patients. However, this study needs to be done on a large scale to assess the impact of coinfection on CD4 count and HIV viral load with proper follow-up of patients every 6 months till at least 2 years.

Role of intrafamilial transmission in high prevalence of hepatitis C virus in Egypt.

BackgroundEgypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Although an effective HCV treatment program has been adopted, it is estimated that the number of newly reported cases in Egypt is still high. Intrafamilial transmission may play a role in the high prevalence of HCV in Egypt. Identification of risk factors for the transmission of HCV may help in decreasing its prevalence and eliminating its infection.AimThe aim of this study was to estimate the prevalence of HCV infection among the household contacts of HCV patients and identify the possible risk factors associated with intrafamilial transmission.MethodsThis study was designed as a cohort study of 90 families of patients with confirmed chronic HCV and 38 families of non-HCV-infected persons. Diagnosis of HCV infection was performed by detection of HCV antibodies by fourth-generation enzyme-linked immunosorbent assay and confirmed by HCV RNA polymerase chain reaction. A pre-prepared questionnaire on risk factors was filled out by the participants. The prevalence of HCV was calculated, and univariate and multivariate analyses were carried out to identify the independent risk factors.ResultsAmong 90 positive-index families, 32 (35.6%) had contact persons with HCV infection compared to two of 38 (5.3%) negative-index families (P < 0.001, odds ratio [OR] = 9.9). Out of 257 index-positive contacts, 38 (14.8%) were infected compared to three of 75 (4%) of index-negative contacts (P = 0.01, OR = 4.3). Infection was associated with older age (6.9% of those aged <20 years, 10.4% of those aged 20–39 years, and 22% of those aged ≥40 years were infected) (P = 0.007). Husbands of infected wives were at a higher risk (33% infected) than wives (13.5%) and sons (16.9%) (P < 0.001). A history of hepatic encephalopathy was the independent predictor of intrafamilial transmission (P < 0.001, OR = 5.4).ConclusionIntrafamilial transmission was found to possibly play a major role in the high prevalence of HCV in Egypt. Transmission was associated with older age and contact with patients with hepatic encephalopathy and was high among husbands of infected wives.

Clinical performance of the VERIS HCV assay for hepatitis C virus RNA quantification

BackgroundDiagnosis of hepatitis C virus (HCV) infection and treatment monitoring rely on detection/quantification of HCV RNA and real-time polymerase chain reaction (PCR) techniques are expected to equivalently quantify the different HCV genotypes. ObjectiveThe clinical performance of the VERIS HCV assay for HCV RNA quantification was compared to that of the Abbott RealTime HCV assay. Study designQualitative concordance and quantitative comparison were evaluated on a first panel of 286 clinical samples containing HCV genotypes 1–6. Forty additional genotype 4 samples were tested to explore genotype 4 HCV RNA underquantification. ResultsQualitative discrepancies were observed for low viral loads (<2 log10 IU/mL) in patients under antiviral therapy and would not have had any impact on patients’ management with the current guidelines for the monitoring of patients on direct-acting antivirals (DAAs). Quantification results were well correlated (R2=0.89) with an overall minimal quantification bias (mean VERIS − Abbott difference) of −0.09 log10 IU/mL. Quantification agreement for genotypes 1, 2 and 3 samples was excellent, but reached −0.57 log10 IU/mL for 46 genotype 4 samples. A lower quantification bias of −0.24 log10 IU/mL was observed when testing 40 additional genotype 4 samples with a second reagent lot. Underquantification was not associated with 5′ untranslated region (UTR) sequence polymorphisms but could be explained by 5′ UTR RNA molecular modeling. ConclusionHCV RNA quantification by the VERIS HCV assay and the Abbott RealTime HCV assay was well correlated for all HCV genotypes, except genotype 4 where 5′ UTR RNA folding may impact quantification. Nevertheless, this underestimation of HCV RNA levels had no impact on clinical use.

Incidence of HCV induced-Esophageal varices in Egypt: Valuable knowledge using data mining analysis.

Esophageal varices is one of the most important comorbidity related liver cirrhosis, patients usually presented with hematemesis, melena, or both, ultimately 20% is the mortality during the first attack, hence we aimed to investigate the incidence of such esophageal varices related chronic Hepatitis C virus (HCV) in randomized Egyptian population.One thousand eighteen Egyptian patients, aged between 17 and 58 years, positive for Hepatitis C virus genotype 4 (HCV-4) by enzyme linked immunosorbent assay Ab and HCV RNA-polymerase chain reaction were screened for the presence of esophageal varices.Incidence of esophageal varices was 62.3%; 635 patients, those with large Esophageal varices (LEVs) was 47.4%; 301 patients. Model for end-stage liver disease (MELD) score has not been significantly improved post variceal band ligation (VBL). Using 2D U/S was useful for EVs prediction.Incidence of esophageal varices in HCV Egyptian patients still high, valuable knowledge would be helpful in clinical field have been discovered by data mining computational intelligent analysis using in practical medicine to improve overall health care.

HEPATITIS C VIRUS (HCV) CORE ANTIGEN AS AN ALTERNATIVE TO PCR FOR HCV, RNA QUANTIFICATION TO EARLY DIAGNOSIS OF HCV INFECTION AMONG BLOOD DONORS

Background: Safety blood transfusion is based on reliable donor screening for transmissible infections such as the hepatitis C virus (HCV) infection. HCV-RNA by polymerase chain reaction (PCR) test is a gold standard test for HCV infection but with three major limitations: liability of RNA molecules, higher costs, and longer turnaround time as compared with HCV core antigen (HCVcAg) testing. Objective: To evaluate HCV core Ag as an alternative to PCR for HCV RNA to early diagnosis of HCV infection among blood donors. Patients and Methods: 4222 blood donors collected between March 2015 and July 2016 at Blood Bank Center of Najran Hospitals, Southwestern Saudia Arabia. Anti-HCV, HBsAg, syphilis and HIV were screened by third generation ELISA. Those reactive to HbsAg, syphilis and/or HIV were excluded. HCV core Ag and HCV RNA by RT-PCR were performed on 76 positive HCV-Ab sera. Results: Among total 4222 blood donors (3837 males (90.88%) and 385 females (9.12%)), 76 (1.8%) were positive for HCV-Ab (72 males; 94.74% and 4 females; 5.26%). HCV core Ag was ≥ 11 fmol/L in 65 cases (85.53%) of HCV Ab positive patients (61 males; 93.85% and 4 females; 6.15%), 3 cases with HCVcAg levels in grey zone (3-11 fmol/L) and 8 cases with HCVcAg ≤ 3 fmol/L all of both were males. HCV RNA was detected in 71/76 (93.42%) of donors with positive HCV-Ab and in 3 of 8 (37.5%) of those with positive HCV-ab and negative HCVcAg. HCVcAg has sensitivity, specificity, PPV and NPV of 97.14, 100, 100 and 99.76 values respectively at a cutoff 2.82 fmol/L compared to HCV RNA test. Conclusion: Higher sensitivity and specificity of HCVcAg with rapid turn around time of the results, and its lower price suggested that can be used alternatively to HCV RNA test in early diagnosis of HCV infection.

The Prevalence of Hepatitis C Virus Infection in Patients With Thalassemia in Zabol City of Iran

Background: Thalassemia patients are at risk of blood borne viral infections because of repeated transfusion of blood products. Objectives: We aimed to determine the prevalence of Hepatitis C Virus (HCV) infection in these patients in Zabol, Iran. Methods: This study was conducted on 152 patients with thalassemia at the center of special diseases of Zabol. Demographic data were collected and serum anti HCV Ab and in seven cases HCV RNA Polymerase Chain Reaction (PCR) was performed. Results: The mean age of patients with thalassemia was 20.1 ± 3.3 that 69.2% of them were male. Thirteen out of 152 patients with thalassemia (8.5%) were HCV Ab positive, which confirmed the polymerase chain reaction (PCR). The prevalence of HCV infection in blood samples before 1995 was significantly higher than after this year (P = 0.043). Conclusions: Considering the high prevalence of hepatitis C in patients, who received blood transfusions, it seems necessary to examine blood products and blood donors more closely in terms of transmissible diseases like Hepatitis C.

Seroprevalence of HCV among Cairo University students in Egypt.

Hepatitis C virus (HCV) is highly prevalent in Egypt. This work aimed at determining the seroprevalence of HCV among Cairo University students. The present study included 3,000 students from Cairo University, Egypt. Blood sample was obtained from each participant to be tested for HCV seromarker. HCV RNA detection by polymerase chain reaction (PCR) was carried out for those with positive anti-HCV. Overall prevalence rate of HCV antibody (anti-HCV) was 4.6%. It showed that the prevalence was relatively higher among females (86/1660; 5.2%) while males (51/1340; 3.8%) with no significant difference. PCR for HCV RNA was detected in 31.4% of the HCV antibody positive subjects (43/137). Which showed statistical significant difference between males (29/51) and females (14/86) at P = 0.001. Despite the prevalence rate reported in the present study was similar to anti-HCV prevalence among persons in the same age group, confirmed that HCV infection is detected among Cairo University students. J. Med. Virol. 88:1384-1387, 2016. © 2016 Wiley Periodicals, Inc.

Tumefactive multiple sclerosis and hepatitis C virus 2a/2C infection: Dual benefit of long-term interferon beta-1a therapy?

Hepatitis C virus (HCV) infection has been implicated in triggering acute disseminated encephalomyelitis but not tumefactive multiple sclerosis. We report the case of a 17-year-old female who presented with a 5-day history of left hemiparesis and hemisensory loss followed by a right third nerve palsy. Tumefactive multiple sclerosis was diagnosed based on the absence of encephalopathic signs, the presence of tumefactive brain lesions, the exclusion of neoplastic and infectious causes of the lesions by biopsy, and the occurrence of relapse after a period of remission. The patient was at risk for HCV infection due to parenteral drug abuse and multiple sexual partners. Serial HCV antibody tests and RNA polymerase chain reaction assays revealed acute HCV infection and genotyping showed HCV genotype 2a/2c. She was treated with high-dose methylprednisolone and discharged with only mild left hand weakness. Interferon beta-1a 30mcg was administered intramuscularly once a week. Remission from HCV infection was achieved in three years without standard anti-HCV therapy. This case suggests that CNS myelin is a potential target of the immune response to HCV 2a/2c infection, the HCV 2a/2c virus may be involved in triggering autoimmune tumefactive brain lesions, and interferon beta-1a is effective against HCV 2a/2c infection. We recommend serial HCV antibody testing and HCV RNA PCR assay, preferably with HCV genotyping, in all patients with acute inflammatory demyelinating diseases of the CNS.

End treatment response and sustained viral response in hepatitis C virus genotype 3 among Pakistani population

BACKGROUND AND OBJECTIVESThis study aimed to determine the end treatment response (ETR) and sustained viral response (SVR) to interferon (IFN) and ribavirin in hepatitis C virus (HCV) genotype 3 in the Pakistani population.DESIGN AND SETTINGSThis is an interventional study conducted from January 2010 to December 2012 in Lyari General Hospital and Abbasi Shaheed Hospital, Karachi, outpatients department.METHODSAll patients with chronic hepatitis C genotype 3 infections were included. Patients with decompensated chronic liver disease, or having coexisting hepatitis B virus/human immunodeficiency virus were excluded. All patients received IFN alpha, 3 million international units (MIU), subcutaneously 3 times weekly and ribavirin >800 mg/d for a period of 6 months. Outcome parameters included ETR (negative polymerase chain reaction [PCR] at the end of therapy), SVR (negative PCR both at the end of treatment and 6 months later), and relapse (PCR negative at the end of treatment but positive 6 months later) were determined.RESULTSA total of 1170 patients were included with a female to male ratio of 1.64:1 and a mean age of 31.6 (8.4) years. Among 1170 patients, 985 completed the therapy as per the protocol, 119 were defaulted (treatment abandoned before completion), and 66 had to stop treatment due to side effects. ETR was 74.1%, SVR was 98%, relapse rate was 1.5%, and 10.1% were nonresponders. SVR was seen only in patients who had achieved an ETR (n=867). SVR was achieved in 848 patients (out of 867) (98%), relapse was seen in 13 (1.5%), and 6 (0.7%) patients lost follow-up after stopping treatment. Patients achieving ETR and SVR had a mean serum alanine aminotransferase of 71.3 (57.1) and 71.0 (56.5), respectively, which is approximately twice the upper normal limit.CONCLUSIONThe conventional IFN and ribavirin therapy in genotype 3 chronic HCV-infected patients gives an ETR and SVR of 74.1% and 98%, respectively.

Preliminary Results of Ozone Therapy as a Possible Treatment for Patients with Chronic Hepatitis C

Medical ozone is more bactericidal, fungicidal, and virucidal than any other natural substance. Some studies proved that ozone infused into donated blood samples can kill viruses 100% of the time. Ozone, because of its special biologic properties, has theoretical and practical attributes to make it a potent hepatitis C virus (HCV) inactivator, which suggests an important role in the therapy for hepatitis C. The study aim is to evaluate the role of ozone therapy in decreasing HCV ribonucleic acid (HCV RNA) load and its effect on the liver enzymes among patients with chronic hepatitis C. This study included 52 patients with chronic hepatitis C (positive polymerase chain reaction [PCR] for HCV RNA and raised serum alanine transaminase [ALT] for more than 6 months). All patients were subjected to meticulous history taking and clinical examination. Complete blood count, liver function tests, and abdominal ultrasonography were requested for all patients. The ozone group included 40 patients who received major autohemotherapy, minor autohemotherapy, and rectal ozone insufflation. The other 12 patients (conventional group) received silymarin and/or multivitamins. There were significant improvements of most of the presenting symptoms of the patients in the ozone group in comparison to the conventional group. ALT and aspartate transaminase (AST) levels normalized in 57.5% and 60% in the ozone group, respectively, in comparison to 16.7% and 8% in the conventional group, respectively. Polymerase chain reaction (PCR) for HCV RNA was negative among 25% and 44.4% after 30 and 60 sessions of ozone therapy, respectively, in comparison to 8% among the conventional group. Ozone therapy significantly improves the clinical symptoms associated with chronic hepatitis C and is associated with normalized ALT and AST levels among a significant number of patients. Ozone therapy is associated with disappearance of HCV RNA from the serum (-ve PCR for HCV RNA) in 25%-45% of patients with chronic hepatitis C.

FREQUENCY OF HCV AND MEAN AGE

Objectives: To know the frequency of HCV in patients with cirrhosis and to know the mean age of patients with cirrhosis. Design: A descriptive study. Setting: Medical Unit Khyber Teaching Hospital Peshawar Period: From Jan 2007 to Jan 2008. Materials &amp; Methods: 100 consecutive cirrhotic patients or those with signs and symptoms of cirrhosis, admitted to the medical units. They were either known cirrhotic orhaving signs and symptoms of chronic liver disease and diagnosed as cirrhotic during their stay in the hospital on the basis of ultrasound findings. The routine investigations including liver function test (LFTs), prothrombin time (PT), activated partial thromboplastin time (APTT), serum albumin were carried out in all patients. Ultrasound was the main tool for the diagnosis of cirrhosis liver. The hepatitis C virus (HCV) statuswas diagnosed by detecting Anti HCV Antibodies by enzyme linked immunosorbent assay (ELISA). Polymerase chain reaction (PCR) for HCV RNA was done only in affording patients. Results: The overall frequency of HCV was 52 in 100 patients. Out of these 52 HCV positive patients, PCR for HCV RNA was positive in 20 patients (38.15%) and the rest of the patients were not able to afford the est. Out of 52 HCV positive patients the number of male were more (1.8:1) as compared to female. The age of the patients ranged from 45-65 years, the majority being from 45 to 65 years with the mean age of 52 years. The stratification of risk factors was not the objective of this study. However, a note was made of exposure to various risk factors. Most of the patients had the history of receiving injections in the past from quacks. Conclusion: It is concluded that chronic HCV infection is the commonest cause of cirrhosis leading to chronic ill health, great economic burden on family and health care system and mortality. As there is no treatment for cirrhosis so prevention, early detection of HCV infection and prompt treatment of HCV infected patients will undoubtedly lead to a decrease in morbidity and mortality from this silent epidemic.

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections

To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.

Do statins reduce hepatitis C RNA titers during routine clinical use?

To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confirmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers. Median HCV RNA titers did not significantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL). For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no significant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with significantly lower viral titers (P < 0.05). There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.

High prevalence of hepatitis C virus infection in the largest province of Pakistan

To estimate the prevalence and spectrum of hepatitis C virus (HCV) infection in the general population of Pakistan. A total of 6817 blood samples were collected randomly from apparently healthy people in the Punjab, Pakistan from March 1999 to April 2001 and September 2006 to August 2007. Detailed socioeconomic information for each participant was recorded. All the samples were tested for anti-HCV antibodies and all seropositive samples were further tested for HCV RNA by polymerase chain reaction (PCR). Of the total 6817 serum samples tested, 998 (14.63%) were positive for anti-HCV antibodies. HCV RNA PCR was detected in 494 (49.50%) anti-HCV-positive samples. The prevalence of anti-HCV antibodies were significantly higher in males (15.09%) than in females (12.3%) (P < 0.009). A significant difference was also noted in the anti-HCV prevalence rate among different age groups tested (P < 0.01). In a multivariate logistic regression analysis, injected drug use (adjusted OR 6.6 [95%CI 4.1-9.9]), blood transfusion (adjusted OR 5.9 [95%CI 2.9-12.3]), pricked with a needle (adjusted OR 2.2 [95%CI 1.6-3.1]), re-use of syringes (adjusted OR 1.7 [95%CI 0.8-3.6]) and being over 35 years old (adjusted OR 1.3 [95%CI 0.9-1.9]) were independent risk factors for HCV infection. The study showed a high seroprevalence of anti-HCV antibodies in a general and apparently healthy population of the Punjab province of Pakistan. Drug injection, blood transfusion and needle stuck were the factors most strongly associated with HCV infection.

A Significant Sex—but Not Elective Cesarean Section—Effect on Mother‐to‐Child Transmission of Hepatitis C Virus Infection

Risk factors for mother-to-child transmission of hepatitis C virus (HCV) are poorly quantified. We conducted a European multicenter prospective study of HCV-infected pregnant women and their infants. Children with > or =2 positive HCV RNA polymerase chain reaction test results and/or anti-HCV antibodies after 18 months of age were considered to be infected. The overall HCV vertical transmission rate was 6.2% (95% confidence interval [CI], 5.0%-7.5%; 91/1479). Girls were twice as likely to be infected as boys (adjusted odds ratio [OR], 2.07 [95% CI, 1.23-3.48]; P=.006). There was no protective effect of elective cesarean section (CS) delivery on HCV vertical transmission (adjusted OR, 1.46 [95% CI, 0.86-2.48]; P=.16). HCV/human immunodeficiency virus-coinfected women more frequently transmitted HCV than did women with HCV infection only, although the difference was not statistically significant (adjusted OR, 1.82 [95% CI, 0.94-3.52]; P=.08). Maternal history of injection drug use, prematurity, and breast-feeding were not significantly associated with transmission. Transmission occurred more frequently from viremic women, but it also occurred from a few nonviremic women. Our results strongly suggest that women should neither be offered an elective CS nor be discouraged from breast-feeding on the basis of HCV infection alone. The sex association is an intriguing finding that probably reflects biological differences in susceptibility or response to infection.

Treatment of Hepatitis C Virus Infection in Thalassemia

Treatment of hepatitis C virus (HCV) in the general population has improved over the last decade. Patients treated with peginterferon alfa (PegIFN) and ribavirin (RBV) combination therapy demonstrate overall 50-55% sustained viral response (SVR) with rates as high as 80% in patients with genotypes 2 and 3. Because RBV induces hemolysis and subsequently increases blood transfusion requirements, combination therapy has been considered contraindicated for hemoglobinopathies. This report reviews the response to interferon alfa and RBV (IFN/RBV) and PegIFN/RBV combination therapies in patients treated in the Northern California Comprehensive Thalassemia Center. A total of six thalassemia major patients were treated with IFN/RBV (n = 5; age: 4-38 years) or with PegIFN/RBV (n = 1; age: 26 years). Quantitative HCV RNA polymerase chain reaction and liver iron level assessment were completed. Transfusion volumes were obtained from patients' medical records. On IFN/RBV combination, four of five patients demonstrated SVR. The one patient on PegIFN/RBV showed end-treatment viral response after 6 months of therapy (genotype 3), but subsequently relapsed. Liver iron pretreatment level ranged from 0.2 to 22 mg/g dry weight, with a mean +/- SD of 7.9 +/- 7.7. Transfusion requirement increased by a median of 43.5% (range: 32-137%). Five of the six patients had liver iron measurements within 1 year following completion of treatment, with quantitative liver iron increasing in two patients by 2.5 mg/g dry weight, decreasing in two patients by 3 and 14 mg/g dry weight, and remaining unchanged in one patient. All patients were able to complete combination therapy, although dose reductions were required. Patients with thalassemia and high iron overload can obtain SVR after combination therapy with rates similar to those in the general population and without significant complications. Although transfusion requirements increased in most patients, iron burden was not necessarily increased.

When Does Mother to Child Transmission of Hepatitis C Virus Occur?

Mother-to-child transmission of hepatitis C virus (HCV) has been reported in up to 10% of cases and is much more likely to occur when the mother is also infected by HIV. Although women with HCV viremia are especially likely to transmit infection, the precise time when transmission takes place is not known. Transmission of HCV was examined in a prospective cohort study using data from the European Pediatric Hepatitis C Network. Fifty-four HCV-infected children were tested by the HCV RNA polymerase chain reaction technique within 3 days of birth. Nearly one third (31%) of newborn infants tested in the first 3 days of life had positive results. Transmission was more likely if the mother was coinfected by HIV, but the difference was not statistically significant. Mode of delivery, gender, and gestational age failed to predict the polymerase chain reaction (PCR) findings. Mean birth weight was significantly lower in infected children, but there was no significant difference when low-birth-weight infants were compared with normal-weight neonates. Breast-fed infants were marginally less likely than formula-fed infants to be PCR-positive. Four of 10 infants born to mothers who tested positive 4 weeks before delivery were themselves PCR-positive, but this was not the case for any of 4 infants born to PCR-negative women. A positive association between PCR positivity in the first 3 days of life and infection by genotype 1 remained significant after adjusting for several possible confounding factors. In 36 infants who were PCR-negative when born, the mean age at the first positive test was 3.9 months. Late intrauterine or intrapartum transmission was considered to be most likely for 27 infants who were PCR-negative at birth but -positive by age 3 months. Peripartum transmission seemed likely for 9 infants who were PCR-negative at birth and PCR-positive for the first time after 3 months. It appears that at least one third of HCV-infected infants, and possibly as many as half of them, acquire infection before birth. Should effective treatment be developed that is safer for pregnant women than are interferon-a and ribavirin, treatment optimally would begin early in pregnancy.