HCV RNA PCR Research Articles

Sustained improvement of psoriasis associated with HCV after virologic response to sofosbuvir/ribavirin

An 18 year old boy attended a dermatology clinic outside our hospital and diagnosed with psoriasis. His skin lesions over both ankles (Fig. 1) did not improve at all with potent local steroids twice for 3 months, then 3 times daily for another 3 months. His dermatologist talked to him about using methotrexate and asked for liver function tests before starting the systemic therapy.His ALT and AST were doubled. The patient came to our Hepatology clinic worried about his elevated liver enzymes. We asked for viral markers. His HCV-Ab was positive, and PCR for HCV-RNA was 650,000 IU/ml.Treatment started with sofosbuvir 400 mg PO once daily plus ribavirin 600 mg at the morning and 400 mg at the evening.After 4 weeks, ALT and AST decreased to normal and PCR for HCV-RNA was <5 IU/ml. All other lab tests were unremarkable. The skin lesions improved markedly (Fig. 2).Now, after 6 months of the end of treatment, sustained virologic response was documented and the skin lesions are almost disappeared without any topical or systemic treatment.

Seroprevalance of hepatitis-c infection in multi-transfused thalassemic children: study from a West Indian tertiary care center

Background: To study the prevalence of hepatitis-C virus infection in multi-transfused thalassemic children and to correlate these patients with age, number of transfusion, serum ferritin levels and transaminases levels.Methods: This study was conducted in the Department of Pediatrics of a Teaching Institute of Rajasthan. It was a hospital based cross sectional study, conducted over a period of 12 months (April 2016- March 2017). Blood sample for Ant-HCV antibody detection was taken at time of follow-up visit in the subspeciality clinic. These samples were processed in central laboratory for hep-C antibody, serum ferritin and transaminases levels. Anti-HCV antibody detection was done by BI-DOT machine. HCV RNA PCR was done to access viral load in all positive cases.Results: A total of 300 patients were enrolled in the study. There were 219 (73%) males and 81 (27%) females. The mean age of the study group was 7.59±3.6 years (range 1.5-18years). At the time of our study 277 (92.4%) cases were on one or the other chelating agent whereas 23 (7.6%) cases were not taking any kind of chelation therapy. Out of 300 patients, 72(24%) cases tested positive for anti HCV antibody. Out of 72 patients only 36(12%) patients had detectable viral load in RNA PCR. Mean age of the HCV positive cases (9.58±3.28) years was higher as compared to HCV negative cases (6.98±3.54). Maximum HCV positivity 20/38 (52.6%) was seen in 12-18 year age group; followed by 33/76 (43.4%) in 9-12yr age group. Significant association was observed between advancing age and prevalence of hepatitis C in thalassemia major patients (p=0.002). The number of blood transfusions received by anti-HCV positive children (Avg. Transfusion 185±98.40 ml/kg/year) was significantly higher than that by anti-HCV negative patients (Avg. Transfusion 102.8±71.20) (p value&lt;0.001). Maximum HCV positive cases 33 (45.83%) had total transfusions &gt;200 in a year followed by 15 (20.83%) cases with 151-200 transfusions (p&lt;0.001).Conclusions: Despite ELISA screening of blood donors, our study demonstrated high (24%) prevalence of transfusion transmitted hepatitis-C virus in thalassemic children which increases with increasing number of transfusions, it also correlates with rising serum ferritin level and SGPT level.

Performance comparison of new generation HCV core antigen test versus HCV RNA test in management of hepatitis C virus infection

The study has evaluated the performance of HCV core antigen (Cag) test by comparing HCV RNA PCR assay which is considered the gold standard for management of HCV infection.Totally, 132 samples sent for HCV RNA (real-time PCR) test were included in the study. Anti-HCV antibody test and HCV Cag test were performed by chemiluminescent enzyme immunoassay (CMEI).Anti-HCV test was positive in all samples. HCV RNA was detected in 112/132 (84.8%) samples, and HCV Cag in 105/132 (79.5%). The most common HCV genotype was genotype 1 (86%). Considering the HCV RNA test as gold standard; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Cag test were found to be 93.75%, 100%, 100%, 74.07% and 94.69%, respectively, and paired test results were detected as highly concordant. A high level of correlation was seen between HCV RNA and Cag tests, however, the concordance between the two tests appeared to be disrupted at viral loads lower than 103IU/mL. On the contrary, the correlation reached significance for the values higher than 103IU/mL. Viral loads were in the 17–2500IU/mL range for the negative results for Cag test. Pearson's correlation coefficient revealed a considerably high correlation.The concordance between HCV RNA and Cag tests was disrupted under a viral load lower than 103IU/mL. Therefore, it would be appropriate to consider cost effectiveness, advantages and limitations of the HCV RNA and Cag tests during the decision on which method to use for patient management.

Retrospective analysis on the diagnostic performances and signal-to-cut-off ratios of the Elecsys Anti-HCV II assay.

Anti-HCV assays are widely used as a screening tool for HCV infection. However, diagnostic performances and effective signal-to-cut-off ratios (S/COs) for predicting true HCV infections would vary according to the assays used. Thus, we evaluated the diagnostic performances of the new Elecsys Anti-HCV assay. A total of 41694 cases tested by the Elecsys Anti-HCV II assay (Roche Diagnostics, Germany) during January 2013 to December 2015 were retrospectively analyzed by comparing with the diagnosis on HCV infections determined by patients' medical records and results of laboratory tests. Excluding 62 cases with unclear history of HCV infection, 430 and 41202 cases were respectively assorted as "true infection" and "no evidence of infection," and 99.85% of the initial results by the Elecsys assay were concordant with the diagnosis on HCV infection. Sensitivity, specificity, positive and negative predictive values were respectively 99.30%, 99.86%, 88.04%, and 99.99%, where the prevalence of the HCV infection was 1.0%. The area under the receiver operating characteristics curve value of the Elecsys assay was 0.9980 (95% confidence interval [CI]=0.9944 to 1.0017). The S/CO by the Elecsys assay for predictive of a true-positive ≥95% of the time was 19.0 (95% CI=15.0 to 25.1). The Elecsys Anti-HCV II assay showed excellent diagnostic performances, particularly in terms of sensitivity, specificity, and NPV. However, the results obtained by this assay with S/CO less than a certain value would need to be retested by HCV RNA PCR or another anti-HCV assay.

Sub-Clinical Thyroid Disorders in Patients With Hepatitis C Before and After Conventional Treatment

Objective: Thyroid dysfunction represents one of the commonest endocrine manifestations of chronic hepatitis C infection, exaggerated by interferon based treatment. The purpose of this study was to assess the frequency of hepatitis C virus and sub-clinical thyroid disorder in patients with hepatitis C before and after treatment. Methods: This is an observational, cross sectional analysis conducted in Lyari general hospital and Abbasi Shaheed hospital from January 2009 to December 2015. Patients with a positive rt-PCR and genotype 3 were included in the study. After a positive rt-PCR, patients were screened by thyroid stimulating hormone before starting the treatment. All patients were given therapy of conventional interferons (3 million units thrice weekly) and ribavirin (800 mg per day in two divided doses) for a period of 6 months. Patient with normal TSH level was included and patients with a co-existing hepatitis B or D were excluded from the study. After 6 months of therapy all patients had a repeat rt-PCR to see the end treatment response to therapy and a thyroid stimulating hormone to screen for thyroid disorders. Results: A total of 129,430 patients have visited the medical outpatient department of which, 4069 were HCV RNA PCR positive. The prevalence of unrecognized hepatitis C Virus was 13.4% in the study population. The prevalence of sub-clinical thyroid disorders was 9%. Of which 6.5% had sub-clinical hypothyroidism and 2.5% had overt or subclinical hyperthyroidism. A total of 2196 patients were included in the analysis. Mean age was 36.22 ±10.01 years range from 16 to 63 years. Among all 36.9% were male and 5.1% were known diabetics. On the whole 14.8% were non-responders, 80.9% achieved an end treatment response and 4.3% lost to follow up. We observed an association between the post treatment TSH level and the ETR of HCV (p=0.015). A statistically significant difference (p<0.001; 95% CI -3.008-1.577) was observed in the thyroid stimulating hormone at the baseline and following the conventional interferon and ribavirin therapy for a period of 6 months. 388 (17.6%) patients had abnormal thyroid function tests after conventional interferon treatment. These 388 patients were further followed up for 6 months. Conclusion: In conclusion, this study results shows 13.4% prevalence of HCV in Karachi and the prevalence of sub-clinical thyroid disorders was 9%, of which 6.5% and 2.5% had overt hypothyroidism and hyperthyroidism respectively.

Hemophilia Liver Transplant Observational Study (HOTS)

Introduction: Hepatitis C is the leading cause of liver disease in individuals with hemophilia (H). HIV co-infection in 80% accelerates HCV disease progression. Although antiretroviral therapy improves HIV survival and slows HCV progression, some ultimately require transplantation. In contrast to non-hemophilic (NH) risk groups, H have 1) longer duration HCV infection with HCV acquisition via clotting factor in the first year of life; and 2) greater bleeding risk due to factor VIII (IX) deficiency in the setting of thrombocytopenia in end-stage liver disease. These risks are important as 1) duration of HCV infection is a significant predictor of liver disease progression; and 2) increased bleeding risk, including gastrointestinal bleeding, increases post-transplant mortality. Several studies have shown that, while post-transplant survival is similar, pre-transplant survival is shorter in HIV/HCV+ H than NH candidates. These studies were small, limiting analysis for predictors of pre-transplant survival.Methods: We conducted a retrospective observational study utilizing United Network for Organ Sharing (UNOS) national transplant registry data, comparing HCV+ H and HCV+ NH candidates. A 7-item case report form was completed on each subject by eight respective transplant centers including 1) hemophilia status (hemophilia A, ICD 286.0; hemophilia B, ICD 286.1); 2) hepatocellular carcinoma status; 3) HIV status; 4) CD4+ count; 5) HIV RNA PCR; 6) HCV RNA PCR; and 7) platelet count, the latter four variables at listing and at transplantation. We performed univariate proportional hazards models for pre-transplant mortality within 90 days of listing, including group and baseline factors. Variables with p<0.1 from univariate models were included in an initial multivariate model. Kaplan-Meier time to-event curves were constructed for transplant candidates, including time to death, time to transplant, and time to MELD 25; and for transplant recipients, including time to death and time to graft loss. Statistical analysis was by SAS version 9.3, Cary NC.Results: We identified 2,502 HCV+ liver transplant candidates, including 144 (5.8%) with HIV infection, 36 (1.4%) with hemophilia, and 1,213 (48.5%) undergoing liver transplantation from eight U.S. university-based transplant centers for the period January 1, 2004 to December 31, 2010. Other than male predominance, 100% vs. 78.0%, and younger age, 41 vs. 48 years, both p<0.0001, baseline data were similar between H and NH. A total of 1,289 candidates were not transplanted; 771 remained alive or were removed from listing pre-transplant; and 518 expired pre-transplant. The most common causes of pre-transplant death included multi-organ failure in 113 (21.8%) and sepsis or infection in 86 (16.6%). Among transplant candidates, the overall pre-transplant patient survival at 90-days and 6-months from listing did not differ between H and NH. In the first 90 days post-listing, time-to-event curves for death and elevated MELD 25 were significantly different between H and NH groups, log-rank, p=0.0001 and 0.02, respectively. In univariate proportional hazards models, pre-transplant mortality within 90-days of listing was associated with higher baseline MELD, HR=1.15, p<0.001, and lower platelet baseline platelet count, HR=1.11 per 25k/µL, p=0.04, and HIV+ status, p=0.003. The hazard of pre-transplant mortality was marginally worse in HIV+ H than HIV+NH candidates, HR=2.8, p=0.08. In multivariate analysis, higher MELD score was significantly associated with pre-transplant mortality (p<0.0001), and the hazard of pre-transplant mortality remained marginally worse in HIV+ H than HIV+ NH, HR=2.0, p=0.24.Conclusion: This observational study confirms MELD is a significant predictor not only of post-transplant survival, but also pre-transplant survival. Despite longer duration HCV infection and greater bleeding risk, there was no significant difference in pre-transplant survival between HIV+ H and NH, likely due to small numbers of hemophilia candidataes missed by retrospective ICD classification. We suggest implementing ICD classification for H in the UNOS system, to enable robust data collection to determine the impact of HCV antiviral therapies on pre- and post-transplant outcomes, and the potential utility of a combination MELD classification that incorporates age at HCV acquisition and platelet count. DisclosuresRagni:Alnylam Pharmaceuticals: Consultancy, Research Funding; SPARK: Research Funding; Biogen: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Consultancy; CSL Behring: Research Funding; Genentech: Research Funding; Novo Nordisk: Research Funding; Shire: Consultancy; Tacere Benitec: Consultancy; Vascular Medicine Institute: Research Funding; OPKO: Research Funding. Sherman:BMS: Research Funding; Gilead: Research Funding; AbbVie: Research Funding; Merck: Consultancy, Research Funding.

Curing HCV Infection with 4-Week-regimen of Sofosbuvir and Ledipasvir: To Be Remembered

Treatment of chronic hepatitis C virus has changed dramatically in the last few years. For genotype 1, a treatment regimen approved is sofosbuvir and ledipasvir for 12 weeks. Recent studies have shown that 8 weeks regimen in patients without cirrhosis could be also effective, but, till now, there are no reports of 4 week successful treatment with this combination. A 59 year-old nurse woman with history of difficult-to-control type II diabetes mellitus was evaluated in the Gastrenterology outpatient clinic due to a positive HCV antibody detected in evaluation of abnormal liver tests. The complete blood count (CBC) was normal. The ALT level was 35 IU/L; AST, 57 IU/L; GGT 56 IU/L, AP 82 IU/L, ALB, 44,3g/L; total bilirrubin 0,8 mg/dL. The HCV infection was confirmed through HCV RNA PCR with a viral load of 1 170 000 IU/mL (6,07 log10), genotype 1b. The cause of infection is unknow but she had a positive HCV antibody from more than 10 years. For staging she performed a transient elastography with a median value of 8.1 KPa, and an abdominal ultrasound that showed no liver nodules or signs of portal hypertension. In 2015 she started antiviral treatment with sofosbuvir (400mg)-ledipasvir (90mg) qd for 12 weeks, but she stopped the drug after 4 weeks due to nausea. The blood tests at 4th week were normal with undetectable HCV RNA. The patient improved with procinetics but she refused to continue the antiviral treatment. Twenty-four weeks after the end of treatment, she was feeling well and the HCV RNA remained undetectable. The patient achieved a sustained virological response after only 4 weeks of sofosbuvir-ledipasvir combination.

Dermatological Manifestations of Pegylated Interferon alfa2a and Ribavirin Combination Therapy in Chronic HCV Patients

Background and study aim: Dermatological adverse events are an existing concern during treatment of chronic hepatitis C virus infection. Pegylated Interferon (peg –IFN- alfa2a) and ribavirin combination therapy is associated with well-characterized dermatological lesions tending towards a uniform entity of dermatitis. A prospective observational study was designed to evaluate the frequency and clinical pattern of cutaneous side effects in a cohort of patients receiving combination therapy of (pegylated interferon alfa2a) and ribavirin for chronic hepatitis C infection. Patients and Methods: This study was carried out at Alahrar Center for treating chronic hepatitis C patients which is one of the centers of the national committee for treating chronic hepatitis C patients (HCV), Zagazig, Sharkia governorate, Egypt over a period of one year starting from January, 2014 to December 2014. A cohort of 116 consecutive, HCV-positive patients to be treated with pegylated interferon alfa2a and ribavirin with standard doses, were prospectively enrolled. After taking an informed consent, detailed history and cutaneous examination, before treatment and then monthly follow up for one year(during the course of treatment) were performed and recorded .All patients were subjected to throughout, routine laboratory investigations before enrollment including, CBC, random blood sugar, complete liver and renal function tests, TSH, Alfa fetoprotein, antibilharzial Ab titre, ANA, P.T, INR, quantitative PCR for HCV-RNA, pregnancy test was performed for the ladies. Results: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photo-sensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 cases) aggravated. Eruptive seborrhoeic keratosis was reported in 1 case. Conclusion: 113/116 patients (97%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 69 cases (Session [CurrentTestPartTermID]%). Pigmented Oral lichen planus was noted in 50 cases (43%) and generalized pigmentation in 32 (27%). Hypertrichosis of eyelashes (trichomegaly) and eyebrows (synophyrs) was observed in 42 (36%) and 40 (34%) cases respectively. Pruritus occurred in 50 cases (43%), aphthous stomatitis was observed in 33 cases (38%), 19 patients (22%) either developed or had worsening of melasma and 23 (27%) developed urticaria. Brittle nails (10 cases), cheilitis (8 cases), glossitis (3 cases), actinic lichen planus (9 cases), greying of hair (3 cases), discoloration of moustache hair (1 case), and photosensitivity (3 cases) were also observed. Preexisting psoriasis (8 cases), and lichen planus (5 case) aggravated. Eruptive seborrhoeic keratosis was rep case).

Evaluation of CD Markers (5, 19, 56) in HCV Patients Undergoing Hemodialysis

Background : The profile of the immune response of B- lymphocytes markers; CD19 + CD5 + and NK cells CD56 + in chronic hepatitis C and end-stage renal disease patients on Hemodialysis is still limited. Objective : to study the peripheral blood immunophenotypic features of NK, B1 and B cells among patients with Hepatitis C virus infection undergoing hemodialysis, compared to normal patients, by three color flow cytometry immunophenotyping. Methodology : Immunophenotypic features of peripheral blood leucocytes were assessed by flow cytometry in two distinct groups: HCV patients with ESRD (CHC+ESRD, n = 15) and HCV patients with normal renal function (CHC, n = 20), Two control groups that were included were as follows: healthy individuals served as a control group with negative HCV-RNA–PCR (Control, n = 15) and patients on hemodialysis with negative HCV-RNA –PCR (ESRD, n = 20). Results : Flow Cytometry detection of B-lymphocytes and NK-cells showed that, the percentage of B lymphocytes (CD19 + ) were significantly increased in (CHC+ESRD) group compared with ESRD group and normal group (P 0.05). The B1 lymphocytes (CD5 + ) were decreased in (CHC) group compared with (CHC+ESRD) group and control subjects, There was a slightly decrease in (CHC+ESRD) group compared with ESRD control group, No statistically significant difference was shown between groups (P>0.05). Conclusions : Chronic hepatitis C patients with ESRD on HD show distinctive phenotypic profile of circulating leucocytes. It may be a result of HCV infection in this particular group of patients and further investigation on larger scale of patients is recommended.

T Cell Immunoglobulin Mucin-3 (TIM-3) Expression on Peripheral Blood Lymphocytes in Chronic Hepatitis Virus C Infection

Introduction: T cell Immunoglobulin Mucin-3 (TIM-3) TIM-3 acts as a negative regulator of (T helper-1)Th1/ (T Cytotoxic-1)Tc1 cell function by triggering cell death upon interaction with its ligand Galectin-9, a feature observed in chronic viral diseases. Objective: To demonstrate the level of expression of TIM-3 on Peripheral Blood Mononuclear cells (PBCs) in cases of chronic HCV as a number of emerging molecules and pathways have been implicated in mediating the Tcell exhaustion characteristic of chronic viral infection. Patients and Methods: This study included 90 subjects, divided up as follows: Group 1 (35 patients) included HCV antibody positive with normal liver functions (Compensated), Group 2 (35 patients) comprised HCV antibody positive patients with abnormal liver functions (decompensated), and controls (Group 3) involved 20 apparently healthy persons (HCV antibody negative persons). The following laboratory investigations were performed for all participants in the 3 groups: Complete Blood Count (CBC), Blood Chemistry (liver functions), Special investigations (Flowcytometric study, and PCR for HCV RNA). Results: Comparing the control, compensated and decompensated groups regarding lymphocytic counts, ratios of TIM-3 positive cells within CD4, CD8, CD14 and CD56 cells in the three groups. Ratio of CD4 cells was higher in the compensated and control groups, than in the decompensated group, with non-significant difference. CD8 cells were maximum in the decompensated groups and minimum in the compensated group, with a significant p value. CD14 cells were maximum in the compensated group, followed by decompensated and minimum in the control group, again with a significant difference. CD56 showed non-significant differences between the three groups. A steady increase in the percentage of TIM +ve CD4, CD8, CD14 and CD 56 cells, with maximum percentages among the decompensated liver disease group, and least percentage among the control group was seen. The differences were significant regarding CD8 and CD56 and highly significant regarding CD4 and CD14 cells. Conclusions: Accumulation of TIM-3+ T cells is associated with functional impairment, and consequently with development of persistent HCV. The present study provides a basis for improving current therapies by simultaneous blockade of multiple inhibitory pathways that could result in additive efficacy without excessive toxicity. These findings have implications for the development of novel immunotherapeutic approaches to this common viral infection.

Occupational exposure to hepatitis infection among Egyptian healthcare workers and hepatitis B vaccination

Background/aim Healthcare workers (HCWs) are at a high risk for blood-borne pathogens due to their contact with patients and contaminated instruments. The present study aimed to determine the risk of exposure to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among Egyptian HCWs in relation to the level of infection control education, the number of hepatitis B vaccine doses received, and the resulting immunity. Participants and methods This cross-sectional study was conducted on 228 HCWs. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody titer, and hepatitis C virus antibody (HCV-Ab) were tested by using the enzyme-linked immunosorbent assay technique. Real-time PCR for both HBV-DNA and HCV-RNA in serum was done with positive hepatitis B surface antigen and HCV-Ab, respectively. Results During the study period, 78% of the HCWs received full HBV vaccination; 73.6% of them were vaccinated in the last 5 years. Lack of protective hepatitis B surface antibody (HBs-Ab) titer was found in 27.2% of the participants. HCV-Ab was positive in 6.14% HCWs, being significantly higher in individuals 40 years of age or older when compared with those under 40. Half of those with positive HCV-Ab had HCV-RNA below the detection limit. Conclusion Implementation of infection control guidelines played a role in reducing the prevalence of HCV infection among HCWs and in vaccinating HCWs in the last 5 years. Adopting safety-engineered devices is required to help in the reduction of needle stick and sharp medical devices injuries and risk for blood-borne infections.

Potential role of interleukin 28B-gene polymorphism and natural immune enhancer treatment response in chronic HCV patients

HCV infection is a major health problem in Egypt. Studies using safe natural products Blue green® tablet showed its antiviral effect. Polymorphisms in the interleukin-28B (IL28B) gene are associated with outcomes from infection with HCV. The rationale of the present study is to evaluate the potential role of interleukin 28B gene polymorphism (IL28B) and natural immuneenhancer treatment response in chronic HCV patients. This study included 100 chronic HCV patients. Patients were classified into two groups: Group I, fifty patients with cirrhosis and advanced liver disease. Patients were unfit INF/ Ribavirin: Group II, fifty patients who refused INF/Ribavirin. Patients were treated with combination of natural products of Blue green® tablet (4 tablets daily which equivalent to 100 mg AFA/30 kg BW), vitamin D, tea spoon field paste of black seeds, olive oil and honey. Alanine Aminotransferase (AST), Aspartate Aminotransferase (ALT), complete blood count (CBC) were measured in the two groups. Detection of HCV-RNA level by quantitative PCR was done before &amp; after 3, 6, 12 and 18 months of treatment. Genomic DNA extracted from all the 100 patient’s blood samples was analyzed for the rs12979860 SNPof IL28B using a real-time polymerase chain technique incorporating SYBR Green. The results showed that, the activities of hepatic marker enzymes (AST and ALT), complete blood pictures (Hb, WBCs and Platelets), HCV RNA PCR, IL 28-B gene polymorphism were non-significantly (p&gt;0.05) differences when compared untreated patients (Group I) and treated patients (Group )were CC genotype before treatment was 8 (34%) &amp; was 13 (26%) after treatment, CT genotype before treatment was 26 (52%) &amp; was 28 (56%) after treatment, TT genotype before treatment was 7 (14%) &amp; was 9 (18%) after treatment. Also, there were non-significant (p&gt;0.05) differences between responder &amp; non-responder in treated patients. In conclusion, the treatmentwith natural immune enhancer in chronic HCV patients showed no significance correlation with IL 28 gene polymorphism

Monocyte-derived dendritic cells in children with chronic hepatitis C: correlation with interferon and ribavirin therapy.

Hepatitis C virus (HCV) infection is a major health problem worldwide. Defective dendritic cell (DC) activation of T cells may underlie poor T-cell responsiveness in HCV infection. To evaluate the DCs' functions in chronically infected HCV patients and its correlation with the response to therapy. This prospective study included 30 chronic hepatitis C (CHC) patients and 30 healthy age-matched and sex-matched controls. The first group received combined pegylated interferon-α-2b (Peg-IFN-α2b)/ribavirin therapy for 48 weeks. A quantitative HCV-RNA PCR was performed for all patients before treatment and at 12, 24, 48, and 24 weeks after treatment. To clarify the functions of DCs, we induced maturation of peripheral DCs from blood samples of CHC patients and healthy controls using Resiquimod (R848). The functions of DCs were assessed by measurement of the levels of IFN-γ and interleukin-10 (IL-10). Sixteen (53.3%) of the patients were treatment responders and the other 14 (46.4%) were nonresponders. The current study showed a statistically significant difference between CHC patients and the control group in IFN-γ production, which was higher in the control group (1.53±0.38 IU/ml) than in the CHC patients (1.19±0.21 IU/ml); in contrast, IL-10 was higher in CHC (249.4±27.6 pg/ml) than the control group (217.0±29.9 pg/ml). However, there was no significant difference between treatment responders and nonresponders in both IFN-γ and IL-10 levels. HCV infection is associated with impaired production of IFN-γ, which may be an indication of a defect in DC function.

HIV, Hepatitis B and C among people who inject drugs: high prevalence of HIV and Hepatitis C RNA positive infections observed in Delhi, India.

BackgroundIndia has large PWID (persons who inject drugs) population estimated at 177,000. PWIDs are at high risk for HIV, Hepatitis B (HBV) and Hepatitis C (HCV) infections. We report the prevalence of HIV, HBV and HCV infections and correlates of HIV-HCV co-infection among male PWIDs in Delhi.Methods3748 male PWIDs were recruited for a longitudinal HIV incidence study. Participants were tested for HBV and HCV infections at their first follow-up visit (FV1) using serum HBV-surface antigen, and HCV-antibody tests followed by HCV RNA PCR, respectively. All PWIDs who were HIV-negative at enrollment, were re-tested for HIV at FV1. Multinomial logistic regression was employed to identify predictors of HIV, HCV and HIV-HCV co-infection.ResultsOverall prevalence of HIV, HBV and HCV among 2,292 participants tested at FV1 was 25.9 %, 9.7 % and 53.7 %, respectively. 6.4 % of the participants had HIV mono-infection, 34.1 % had HCV mono-infection, and 19.6 % had HIV-HCV co-infection. 26 % of HIV-positive participants without HCV were HBsAg positive.In the regression model, having practiced at least one risky injection in the past month (relative risk ratio (RRR): 1.38; 95 % CI: 1.01-1.89) and not knowing his own HIV status (RRR: 1.65, 95 % CI: 1.25-2.17) were independent predictors for HIV-HCV co-infection. Longer duration of drug injections was associated with a higher likelihood of HCV mono-infection (2–5 years RRR: 2.13; 6–10 years RRR: 2.74; ≥11 years RRR: 3.14) and HIV-HCV co-infection (2–5 years RRR: 5.14; 6–10 years RRR: 8.53; >11 years RRR: 8.03). Higher frequency of injection days/month was associated with a higher likelihood of HCV mono-infection (≤10 days/month RRR: 1.61; 11–20 days/month RRR: 3.15; 21–30 days/month RRR: 3.47) and HIV-HCV co-infections (≤10 days/month RRR: 2.26; 11–20 days/month RRR: 3.46; 21–30 days/month RRR: 4.83).ConclusionsWe report a high prevalence of HIV, HCV and HIV-HCV co-infection among male PWIDs in Delhi. A tenth of the participants were HBsAg positive. Targeted Intervention programs should make HBV/HCV testing, prevention and care more accessible for PWIDs.

Underweight May Be a Risk Factor for Lower Bone Density in Chronic Hepatitis C Infected Male Patients

Background/Aim of the study: Osteoporosis and osteopenia are well known complications in patients with chronic liver disease, we aimed to investigate Egyptian male patients with chronic hepatitis C infection as regard the bone mineral density and risk factors for osteoporosis in this subpopulation and correlating it to BMI (body mass index). Patients and methods: One Hundred ninety-three Egyptian male patients with hepatitis C virus CLD has been enrolled and consented: 116 under weight and 77 normal weight, Chronic HCV infection was confirmed by positive anti-HCV antibodies and HCV RNA PCR. Cirrhosis was diagnosed based on sonographic and laboratory criteria. Noninvasive methods were used: the FibroScan test was used for assessment of liver fibrosis. Blood was drawn for routine tests included total serum calcium, phosphate, creatinine and total alkaline phosphatase using standard methods. 25-hydroxy vitamin D (25OHD) were done. Bone mineral density: BMD of the lumbar spine, femoral neck: using dual energy x-ray absorptiometry (DEXA)Scan were analyzed by the same technician. Results were correlated to Body mass index and Serum vitamin D level. Results: Demographic Data and Clinical Characteristics of Under and Normal Weight Chronic Hepatitis C Men were recorded, the results showed statistically significant correlations between under and normal weight HCV patients regarding BMI and BMD (in right hip and femoral neck, p values were 0.002 and 0.004, respectively). Subnormal 25 hydroxy vitamin D levels were present in 64% of the underweight patients and 51% of the normal weight patients with no significant differences between both groups. Conclusion: the body weight and BMI might be more detrimental for low BMD in male patients with CLD secondary to HCV infection rather than vitamin D status.

Cryoglobulinemic Vasculitis Occurring With Initiation of Interferon and Sofosbuvir for Treatment of Hepatitis C

Introduction: A 58-year-old Hispanic woman presented with a 2-day history of a pruritic rash that had started on her hands before spreading to her abdomen, chest, upper extremities, and lower extremities. Her history was significant for chronic hepatitis C (HCV), genotype 1, but no prior history of vasculitis. She had been started on ribavirin, peginterferon alfa 2-a, and sofosbuvir 6 weeks prior to admission, with an undetectable HCV RNA PCR after 4 weeks. However, treatment had been stopped 2 weeks prior to admission due to neutropenia (ANC 400 cells/mL). Her temperature on admission was 101.7 °F. On physical exam, she had edematous pink plaques on the dorsal hands, elbows, and proximal bilateral lower extremities. There were purpuric papules and plaques on the bilateral midlower thighs, shins, ankles, and feet. White blood cell count was 2,4000 cells/μL with normal differential, hemoglobin 11.9 mg/dL, platelets 119000 cells/μL, and creatinine 0.7 mg/dL. Urinalysis did not show proteinuria. Liver function and iron studies were unremarkable. ANA, ANCA, CRP, ESR, HIV, anticardiolipin antibodies, beta-2-glycoprotein, and lupus anticoagulant were normal. Cryoglobulins were positive, with low complement levels, mildly elevated rheumatoid factor, and undetectable HCV viral load. Punch biopsy showed leukocytoclastic vasculitis. She was started on a steroid taper, and at 2-week follow-up, her rash had resolved completely. Here, we present a case of a patient with cryoglobulinemic vasculitis on co-therapy with interferon (IFN) and sofosbuvir. Cryoglobulins may be seen in 40-56% of patients with HCV infection, with vasculitis only seen in <5% of patients with cryoglobulinemia. In these cases, vasculitis usually improves with treatment of HCV. However, there have been reports of cryoglobulinemic vasculitis initially appearing after initiation of treatment with interferon, with unknown rates of occurrence in the setting of co-therapy with sofosbuvir. Treatment in these cases usually consists of corticosteroids with or without immunosuppression using cyclophosphamide. In our patient’s case, administration of prednisone led to complete resolution of vasculitis, with no residual purpura, neuropathy, or renal insufficiency. Viral load remained undetectable at all times. This shows the importance of close monitoring of patients while on treatment with interferon and sofosbuvir, regardless of the viral load.

Hepatitis C viremia patterns in incident hepatitis C infection and one year later in 150 prospectively tested persons who inject drugs.

ObjectivesTo assess HCV viremia levels just before, during and one year after anti-HCV seroconversion in people who inject drugs (PWID).MethodsPWID enrolling into a needle exchange program in Malmö, Sweden, 1997–2005 constituted the source population. Sera were obtained at enrolment and at approximately 3–4 monthly intervals afterwards, and were initially tested for anti-HIV, HBsAg/anti-HBc and anti-HCV and thereafter for markers previously negative. Seroconversion to anti-HCV had occurred during the study period in 186 out of 332 seronegative subjects. In these anti-HCV seroconverters, quantitative HCV RNA PCR was retrospectively performed on frozen sera to determine viremia levels in the last anti-HCV negative, the first anti-HCV positive and in one year follow-up samples.ResultsAmong 150 subjects seroconverting to anti-HCV with samples available from all three defined time-points, eight different patterns of viremia were observed. Spontaneous clearance at one year was noted in 48 cases (32%) and was associated with female gender (p = 0.03, CI 0.17–1.00). In 13 cases HCV-RNA was not detected in any study sample. Among 61 subjects with pre-seroconversion viremia, viral load was significantly higher in the pre-seroconversion samples compared to subsequent samples. For the whole group, viral load declined to undetectable levels at seroconversion in 28% of cases (but with recurrent viremia in 15%).ConclusionsDifferent patterns of HCV RNA kinetics were observed among PWID with documented seroconversion to anti-HCV. The frequently observed absence of detectable HCV RNA in the first anti-HCV positive sample (irrespective of subsequent viremia) demonstrates the importance of repeated sampling and RNA testing for determination of the outcome of acute infection.

Su1065 Longer Therapy With 48 Weeks of Pegylated Interferon and Ribavirin (PEG IFN+RBV) Is Superior to 24 Weeks in Patients With Treatment-Naive Hepatitis C Virus Genotype 6 (HCV-6): A Meta-Analysis of 641 Patients

Background: HCV-6 is common in patients from Southeast Asia and the surrounding regions where HCV prevalence can be up to 6%. Optimal treatment duration for HCV-6 is unknown given inconclusive evidence from studies with varying methodologies and small sample sizes. Our goal was to assess the optimal treatment duration for these patients. Methods: We performed a literature search for ‘genotype 6' in the MEDLINE and EMBASE databases (without MEDLINE-indexed articles) in September 2013, which produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/ liver conferences in 2012 and 2013. Inclusion criteria were: original study, treatment-naive patients, and minimum sample size ( ≥10 HCV-6 patients). Exclusion criteria were: coinfections with hepatitis B virus, HIV, other HCV genotypes, and/or other liver diseases. Only patients who received PEG IFN+RBV were included in the analysis. All literature searches and data extraction were performed independently by two authors. Primary outcome was pooled sustained virologic response (SVR, undetectable HCV RNA PCR 24 weeks after end of therapy). Cochrane Q-test (p-value of 0.10) and I-squared statistic (> 50%) were utilized to assess heterogeneity. Results: A total of 13 studies with 641 patients were included in the analysis. Pooled SVR estimate, by random effects model (Q-value=38.4, p-value <0.001; I-squared=68.7%), was 77% (CI=70-83%) for all patients and 79% (CI=73-84%) and 59% (CI=46-70%) for 48-week group and for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 vs. 24 weeks, OR 1.9 (CI=1.08-3.2, p=0.026) (Figure 1). In studies with direct comparison and intention-to-treat analysis only, there was a trend for higher SVR in patients treated for 48 vs. 24 weeks, OR 1.63 (CI=0.91-2.92, p=0.10) (Figure 2). SVR in patients with rapid virologic response (RVR, undetectable HCV RNA PCR after 4 weeks of therapy) treated for 48 weeks and 24 weeks was 86.1% (CI=77.5-91.8%) and 77.6% (CI=63.1-87.5%), respectively. Those with RVR had better treatment response than those without RVR: OR 18.33 (CI= 5.67-59.26, p<0.001) for the 48-week group and OR 18.61 (CI=2.51-137.91, p=0.004) for the 24-week group. When directly compared, there was no statistical significance in SVR in patients with RVR treated for 48 or 24 weeks, OR 1.74 (CI=0.65-4.64, p=0.271). Conclusions: Patients treated for 48 weeks had higher SVR than those treated for 24 weeks (79% vs. 59%, respectively); however, patients with RVR appear to have similar treatment responses regardless of treatment duration. HCV-6 patients treated with PEG IFN+RBV should be treated for 24 weeks if there is RVR and 48 weeks if not.

Lopinavir/Ritonavir Pharmacokinetics, Efficacy, and Safety in HIV and Hepatitis B or C Coinfected Adults Without Symptoms of Hepatic Impairment

Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome. Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation. None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection. Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data.

P1113 CHOLESTEROL METABOLISM DURING PEG-IFN + RBV + TVR TREATMENT

Background: HCV-6 is common in patients from Southeast Asia and the surrounding regions where HCV prevalence can be up to 6%. Optimal treatment duration for HCV-6 is unknown given inconclusive evidence from studies with varying methodologies and small sample sizes. Our goal was to assess the optimal treatment duration for these patients. Methods: We performed a literature search for ‘genotype 6' in the MEDLINE and EMBASE databases (without MEDLINE-indexed articles) in September 2013, which produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/ liver conferences in 2012 and 2013. Inclusion criteria were: original study, treatment-naive patients, and minimum sample size ( ≥10 HCV-6 patients). Exclusion criteria were: coinfections with hepatitis B virus, HIV, other HCV genotypes, and/or other liver diseases. Only patients who received PEG IFN+RBV were included in the analysis. All literature searches and data extraction were performed independently by two authors. Primary outcome was pooled sustained virologic response (SVR, undetectable HCV RNA PCR 24 weeks after end of therapy). Cochrane Q-test (p-value of 0.10) and I-squared statistic (> 50%) were utilized to assess heterogeneity. Results: A total of 13 studies with 641 patients were included in the analysis. Pooled SVR estimate, by random effects model (Q-value=38.4, p-value <0.001; I-squared=68.7%), was 77% (CI=70-83%) for all patients and 79% (CI=73-84%) and 59% (CI=46-70%) for 48-week group and for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 vs. 24 weeks, OR 1.9 (CI=1.08-3.2, p=0.026) (Figure 1). In studies with direct comparison and intention-to-treat analysis only, there was a trend for higher SVR in patients treated for 48 vs. 24 weeks, OR 1.63 (CI=0.91-2.92, p=0.10) (Figure 2). SVR in patients with rapid virologic response (RVR, undetectable HCV RNA PCR after 4 weeks of therapy) treated for 48 weeks and 24 weeks was 86.1% (CI=77.5-91.8%) and 77.6% (CI=63.1-87.5%), respectively. Those with RVR had better treatment response than those without RVR: OR 18.33 (CI= 5.67-59.26, p<0.001) for the 48-week group and OR 18.61 (CI=2.51-137.91, p=0.004) for the 24-week group. When directly compared, there was no statistical significance in SVR in patients with RVR treated for 48 or 24 weeks, OR 1.74 (CI=0.65-4.64, p=0.271). Conclusions: Patients treated for 48 weeks had higher SVR than those treated for 24 weeks (79% vs. 59%, respectively); however, patients with RVR appear to have similar treatment responses regardless of treatment duration. HCV-6 patients treated with PEG IFN+RBV should be treated for 24 weeks if there is RVR and 48 weeks if not.