Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK)

<p>Abstract</p> <p>Background</p> <p>Interferon based therapy is used to eradicate the Hepatitis C Virus from the bodies of the infected individuals. HCV is highly prevalent in Khyber Pakhtunkhwa (KPK) that is why it is important to determine the response of standard interferon based therapy in Chronic HCV patients of the region.</p> <p>Study design</p> <p>A total of 174 patients were selected for interferon based therapy. The patients were selected from four different regions of KPK. After confirmation of active HCV infection by Real Time PCR, standard interferon with ribavirn was given to patients for 6 months. After completion of therapy, end of treatment virologic response (ETR) was calculated.</p> <p>Results</p> <p>Out of total 174 patients, 130 (74.71%) showed ETR and 44 (25.28%) did not show ETR. In district Bunir, out of 52 patients, 36 (69.23%) showed ETR and 16 (30.79%) did not show ETR. In district Mardan, out of the total 74 patients, 66 (89.18%) were negative for HCV RNA and 8 (10.81%) were resistant to therapy. In Peshawar, out of 22, 16 (60%) were negative and 6 (40%) were positive for HCV RNA at the end of 6 months therapy. In the Federally Administered Tribal Area (FATA), out of 18 only 10 (55.5%) were negative and 8 (44.45%) were positive for active HCV infection.</p> <p>Conclusion</p> <p>It is concluded that the response of antiviral therapy against HCV infection in chronic HCV patients of KPK province is 74.71%. The high response rate may be due to the prevalence of IFN-responsive HCV genotypes (2 and 3) in KPK.</p

An IL28B Genotype-Based Clinical Prediction Model for Treatment of Chronic Hepatitis C

BACKGROUND:Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS:HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). RESULTS:Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION:A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC

Ribavirin Enhances IFN-α Signalling and MxA Expression: A Novel Immune Modulation Mechanism during Treatment of HCV

The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG) expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV

Physicians' preference values for hepatitis C health states and antiviral therapy: A survey

BACKGROUND: Physicians' perspectives regarding hepatitis C shape their approach to patient management. We used utility analysis to evaluate physicians' perceptions of hepatitis C-related health states (HS) and their threshold to recommend treatment. METHODS: A written questionnaire was administered to practicing physicians. They were asked to rate hepatitis C health states on a visual analog scale ranging from 0% (death) to 100% (health without hepatitis C). Physicians then judged quality of life associated with the side effects of antiviral therapy for hepatitis C and indicated the sustained virological response rate that they would require to recommend treatment. RESULTS: One hundred and thirteen physicians from five states were included. Median utility ratings for hepatitis C health states declined significantly with increasing severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms, Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of antiviral therapy was 47%, suggesting a 53% reduction from good health. That was similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median threshold value for recommending treatment was a sustained response rate of 60%. CONCLUSIONS: 1) Physicians' utility ratings for hepatitis C health states were inversely related to the severity of disease manifestations described. 2) Physicians viewed side effects of therapy unfavorably and indicated that on average, they would require a 60% sustained response rate before recommending treatment, which far exceeds the efficacy of current antiviral therapy for hepatitis C in the majority of patients

Reasons for compliance or noncompliance with advice to test for hepatitis C via an internet-mediated blood screening service: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is mainly transmitted by exposure to infected blood, and can lead to liver cirrhosis and liver cancer. Since the onset of HCV and the development of liver cirrhosis usually are asymptomatic, many HCV-infected individuals are still undiagnosed. To identify individuals infected with HCV in the general population, a low threshold, internet-mediated blood testing service was set up. We performed a qualitative study examining reasons for compliance and noncompliance with advice to test for HCV via the online blood testing service.</p> <p>Methods</p> <p>Semistructured telephone interviews were conducted with 33 website visitors who had been advised to test for HCV (18 testers, 15 non-testers). Transcribed interviews were analyzed qualitatively and interpreted using psychosocial theories of health behavior.</p> <p>Results</p> <p>Reasons for testing pertaining to the online service were: the testing procedure is autonomous, personalized test advice is provided online, reminder emails are sent, and there is an online planning tool. Reasons for testing not specific to the online service were: knowing one's status can prevent liver disease and further transmission of HCV, HCV is curable, testing can provide reassurance, physical complaints are present, and there is liver disease in one's social environment. Service-related reasons for not testing pertained to inconvenient testing facilities, a lack of commitment due to the low threshold character of the service, computer/printing problems, and incorrectly interpreting an online planning tool. The reasons for not testing that are not specific to the online service were: the belief that personal risk is low, the absence of symptoms, low perceived urgency for testing and treatment, fear of the consequences of a positive test result, avoiding threatening information, and a discouraging social environment.</p> <p>Conclusions</p> <p>Features specific to the online service played a significant role in motivation to test for HCV above and beyond the more conventional perceived health benefits of HCV testing. However, some online specific features were considered problematic and need to be adapted. Methods and strategies for dealing with these impeding factors and for improving compliance with testing via the online service are outlined.</p

Patient acceptance of universal screening for hepatitis C virus infection

<p>Abstract</p> <p>Background</p> <p>In the United States, about 70% of 2.9-3.7 million people with hepatitis C (HCV) are unaware of their infection. Although universal screening might be a cost-effective way to identify infections, prevent morbidity, and reduce transmission, few efforts have been made to determine patient opinions about new approaches to screening.</p> <p>Methods</p> <p>We surveyed 200 patients in August 2010 at five outpatient clinics of a major public urban medical center in Seattle, WA, with an 85.8% response rate.</p> <p>Results</p> <p>The sample was 55.3% women, median 47 years of age, and 56.3% white and 32.7% African or African-American; 9.5% and 2.5% reported testing positive for HCV and HIV, respectively. The vast majority of patients supported universal screening for HCV. When presented with three options for screening, 48% preferred universal testing without being informed that they were being tested or provided with negative results, 37% preferred testing with the chance to "opt-out" of being tested and without being provided with negative results, and 15% preferred testing based on clinician judgment. Results were similar for HIV screening.</p> <p>Conclusions</p> <p>Patients support universal screening for HCV, even if that screening involves testing without prior consent or the routine provision of negative test results. Current screening guidelines and procedures should be reconsidered in light of patient priorities.</p

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

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Desmoplastic small round cell tumour in a 74 year old man: an uncommon cause of ascites (case report)

A rare case is provided of a 74 year old man who presented with ascites of unknown etiology. CT scan of the abdomen revealed extensive omental caking, and omental biopsy cytogenetics showed findings in keeping with a diagnosis of desmoplastic small round cell tumour (DSRCT). This case is unique in that it involves a significantly older patient, negative WT1 immunohistochemical staining, and negative cytology. Despite repeated paracenteses and fluid management, the patient died in hospital secondary to renal complications

A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents