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Objective: To determine the frequency of thyroid dysfunction among patients with chronic hepatitis C receiving Conventional Interferon and Ribavirin combination therapy and to compare the frequency of thyroid dysfunction among patients with thyroid peroxidase positive and negative antibodies among these patients. Study Design: Cross-sectional study. Place and Duration of Study: Gastroenterology Department of Medicine, Combined Military Hospital, Lahore Pakistan, from Jan to Jul 2017. Methodology: Patients reporting chronic hepatitis C, fulfilling the required selection criteria, and received conventional Interferon and Ribavirin therapy were included. A thyroid Function test was performed at enrollment, week-12 and week-24. The outcome was measured at week 24 by the end of treatment. Anti-Thyroid Peroxidase antibody level was measured at the time of enrollment. Results: One hundred and fifty-seven patients were enrolled in the study. There was no difference in demographic data comparison. At the end of therapy, 5 (29.41%) male patients and 12 (70.59%) female patients developed TD, with the p-value of 0.019, which is statistically significant. 28 (17.83%) out of 157 patients had positive anti-TPO at baseline. The inferential analysis showed that there were significantly higher positive rates of pre-treatment anti-TPO in patients with TD (16 (94.11%) out of 17) when compared with patients with normal baseline anti-TPO (1 (5.89%) of 17), with the p-value of 0.001. Conclusion: Pre-treatment anti-Thyroid Peroxidase antibodies and female gender are the most significant risk factors for developing Thyroid Dysfunction during Interferon and Ribavirin therapy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of SOF/DCV/RBV combination to treat CHC patients at a tertiary care hospital in South Punjab. Study Design: Prospective Study. Setting: Nishtar Medical University Multan. Period: October 2019 to August 2020. Material & Methods: Patients of CHC of any genotype were enrolled prospectively. They were treated with 12 weeks course of SOF/DCV/RBV combination. Effectiveness was evaluated by end of treatment response (ETR) and sustained virological response (SVR) at 12 and 24 weeks post-treatment. Adverse events were recorded for safety analysis. Results: We analyzed data of 102 patients of CHC (40 males and 62 females). The mean age was 40.04 + 10.22 years. Mean weight was 67.24 + 11.78 kg, while mean body mass index (BMI) was 26.32 + 4.58 kg/m². Eighty patients belonged to low socio-economic status, while 22 belonged to middle socio-economic status. Sixty-four had a rural background, while 38 were from urban background. Seventy-four patients had no co-morbid condition; 16 (15.7%) had diabetes and 12 (11.8%) patients had co-morbid hypertension. Ninety percent of the patients did not have cirrhosis; 6% had compensated liver disease, while 4 % had decompensated liver disease. All the patients achieved undetectable HCV RNA at the end of treatment and 12 weeks after completion of treatment, while SVR at 24 weeks was achieved in 98% of patients. Only 2 patients discontinued treatment as a result of side effects. The most common side effects reported include fatigue, headache and fever. Conclusion: CHC is a grave problem in developing countries like Pakistan. The SOF/DCV/RBV combination is very effective in eradicating CHC and has a very good side effect profile as well. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of Sofosbuvir (SOF) and Daclatasvir (DCV) in patients with chronic hepatitis C (CHC), compensated cirrhosis (CC) and decompensated cirrhosis (DCLD) either treatment naïve or experienced. Methods: This was a prospective, observational study, conducted from January 2017 to December 2018 at Jinnah Postgraduate Medical Centre, Karachi. All patients above 12 years of age with detectable HCV RNA PCR were included. Patients were divided into three groups: CHC, CC and DCLD. SOF and DCV for 12 or 24 weeks were given. Ribavirin (RBV) was given to treatment experienced and cirrhotic patients. Primary outcome was End of Treatment Response (ETR) and secondary outcome was Sustained Virological Response (SVR) at post treatment week 12 or 24. Results: Total 300 patients with mean age of 40.49 ± 13.86 were enrolled. Majority were females 174 (58%). CHC were 200 (66.6%) while cirrhotic were 100 (33.4%). Treatment naïve patients were 267 (89%) and 33 (11%) patients were experienced. Most common genotype was 3 (83%). ETR was achieved in 292 (97.33%) and SVR in 265 (88.33%) patients respectively. Conclusion: SOF plus DCV with or without RBV is a highly effective treatment for chronic HCV and is still used in many centers of Pakistan. This regimen has excellent results for GT-3. The outcomes are mainly influenced by the presence or absence of cirrhosis. [ABSTRACT FROM AUTHOR]

HCV infects nearly 10 million patients in Pakistan, genotype 3 is the predominant genotype. Liver transplant used to be the only option in patients with decompensated cirrhosis before the emerging role of DAAs. Clinical trials have suggested that successful treatment of HCV in this group results in early improvement in liver function although long term benefit is not yet known. Objectives: To measure clinical and laboratory parameter improvement after successful eradication of hepatitis C in cirrhotics. To study any events of decompensation while on treatment. To measure incidence of HCC on/after treatment. Study Design: A retrospective, observational study. Setting: Fatima Memorial Hospital, Lahore. Period: July 2015-April 2017. Material & Methods: We included patients with compensated and decompensated cirrhosis with a CTP score ranging from A5 to C12, treated with sofosbuvir and ribavirin or pegylated interferon sofosbuvir and ribavirin. Data analyzed at the initiation, at the end, 12 weeks and 24 weeks post treatment. Results: A total of 191 (98 male and 93 female) patients were included in our study. There was statistically significant improvement in albumin, bilirubin, AFP, platelet count, CTP and MELD scores but not in INR. One patient developed ascites and another developed hepatic encephalopathy. Four patients developed HCC during follow up after completion of antiviral therapy. Conclusions: 1) Successful treatment of cirrhotic patients leads to improvement in clinical and laboratory parameters. 2) Need for continued surveillance for HCC in patients with cirrhosis remains after successful antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known.Methods: We prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy.Results: A total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen.Conclusion: In a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC. [ABSTRACT FROM AUTHOR]

Aim: we aimed to determine the virological response and safety of Sofosbuvir-based direct-acting antiviral agents (DAAs) in chronic hepatitis C (CHC) patients on long-term hemodialysis (HD). Background: With the advent of interferon-free DAAs, the treatment of CHC has been revolutionized. Pakistan is among the countries where novel sofosbuvir (SOF)-free antiviral agents are not available. Methods: This non-randomized, single-arm, open-label study enrolled all HD patients with chronic HCV infection after informed consent. They were treated with SOF in combination with Ribavirin (RBV) with either interferon (IFN group) or daclatasvir (DAC group), with the virological response assessed according to standard guidelines. Data were analyzed using SPSS version 20.00. Results: Out of 133 patients, the majority (72.9%) were males with the mean age of 31.92 ± 9.88 years. Most patients (50.3%) had HCV genotype (GN) 1, followed by GN 3 in 42.9%, 4 in 1.48% and 2 in 0.7%, while mix GN was documented in 6 (4.4%) patients. Among these, 60 (45.1 %) patients received standard SOF, IFN, and RBV (IFN group) and 73 (54.9 %) received SOF, DAC and RBV (DAC group). End of treatment and sustained virological response at 12 weeks post-treatment were achieved in 133 (100%) and 129 (97 %) patients, respectively. The adverse effects were anemia in 58 (43.6 %) patients and elevated alanine transaminases in 11 (8.1%) patients. Conclusion: SOF in combination with either IFN or DAC is an equally efficacious and effective treatment regimen for patients on maintenance HD, especially in resource-poor countries. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects on ALT normalization in the first month by SOFOS/RIB therapy versus SOFOS/DAC therapy in HCV infected individuals in Pakistan. Study Design: Cross-sectional comparative study. Material and Methods: A cross-sectional analysis was performed in a total of 200 Hepatitis C infected patients, sex, history of diabetes mellitus, prior interferon therapy, decrease in hemoglobin >2 gm/dl in 1st month and rise in serum bilirubin in 1st month was the qualitative variables and the quantitative variables were age, weight, baseline hemoglobin, baseline bilirubin at week 4 of treatment. The statistical relation of the mentioned variables was checked using SPSS version 15 on the basis of data collected. Results: Out of total 200 patients, 47% (94) were males, 53% (106) were females, 28% (56) patients were diabetic & 44.5% (89) patients had history of prior interferon therapy, 28.5% (57) patients were having low hemoglobin levels before starting above mentioned treatment. Both the groups completed the treatments A & B for 24 &12 weeks respectively & collected data showed the superiority of treatment B to treatment A as no decrease in hemoglobin (p=0.000), & no rise in serum bilirubin(p=0.000) during 1st month of treatment while serum bilirubin was 93 % in treatment B and 73 % in treatment A. Conclusion: The results concluded that treatment B (Sofosbuvir / Daclatasvir for 12 weeks) is superior antihepatitis C therapy as compared to the treatment A (Sofosbuvir / Ribavirin for 24 weeks) in order to achieve ALT normalization in the first month of therapy in Pakistani population. Ribavirin should be avoided to prevent hemolytic anemia as well. [ABSTRACT FROM AUTHOR]

Background The annual global deaths from viral hepatitis is 1.4 million. Pakistan has the second highest burden of hepatitis C in the world. There is dire need to evaluate the response of new direct acting antivirals for the treatment of hepatitis C patients in Pakistan. World Health Organization has developed a strategy to treat 80% of HCV patients by 2030. In Pakistan, HCV treatment rate is 1%. The aim of the study was to analyze the effect of Sofosbuvir plus Ribavirin therapy on HCV patients in Pakistan. Methods An observational study was conducted at Fauji Foundation Hospital Rawalpindi from November-2016 to July-2017. All the drugs were administered according to the guidelines of Asia Pacific Association for the Study of Liver (APASL) for the treatment of HCV patients. A total 327 chronic HCV patients were enrolled in the study and 304 completed the treatment. Patients belonged to three different groups including treatment: Naïve patients (n = 107), Non-Responder patients (n = 126) and patients who relapsed to Interferon therapy (n = 71). All the patients were given Sofosbuvir plus Ribavirin therapy for 24 weeks and the early virological response (EVR) and end treatment response (ETR) was calculated. Different parameters including patient age, viral load, viral genotype, blood picture, ultrasound findings and liver function tests were also studied. Results Out of 304 patients, 301 (99%) achieved EVR and 300 achieved ETR (98.7%). End treatment response was 95.6% in HCV genotype 1 and 98.9% in HCV genotype 3 patients. ETR was 99.06% in treatment Naïve, 99.20% in non-responders and 97.18% in previously relapsed patients. We did not find the association of any host and viral factor in the determination of EVR and ETR. Conclusion The Sofosbuvir plus Ribavirin treatment is highly effective, safe and cost-effective for the treatment of hepatitis C patients in Pakistan. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effectiveness of daclatasvir and sofosbuvir in treating hepatitis C genotype 3a patients. Material and Methods This was a prospective interventional study. Consecutive non probability sampling technique was followed. It was carried out in Department of Medicine KRL hospital Islamabad, Pakistan from February 2017 to June 2018. This study included 80 patients who were infected with hepatitis C virus. Age ranged from 17-83 years. Amongst them 70 were treatment naive while 10 has received Pegylated Interferon and ribavirin in the past. Of treatment experienced 7 out of 10 patients had achieved SVR. Before starting treatment baseline laboratory tests were done and recorded. Quantitative PCR for HCV RNA and Genotyping was done. All patients received treatment for 3 months. Patients had a follow up every two weeks. Quantitative PCR for HCV RNA was performed at the end of treatment,3 months and 6 months after completion of treatment. Response rates were recorded. Data was analysed using statistical package for social sciences version 17 (SPSS 17). Results: Out of 80 patients54 (67%) were females and 26 (33%) were males. All patients were of genotype 3a. 70 patients (87%) had never experienced treatment before and 10 patients(13%) had previous treatment with pegylated interferon and ribavirin. End of treatment response was observed in 98.8% of patients while sustained virological response(SVR 12) and SVR 24 was observed in 96.25% of patients. Side effects mainly constitutional symptoms occured in about one tenth of patients. Conclusion: Directly acting antiviral drugs(DAA) have improved outlook in hepatitis C treatment while concomitantly reducing the duration of treatment and has high safety profile. [ABSTRACT FROM AUTHOR]

Crimean Congo Hemorrhagic Fever (CCHF) one of the fatal viral infections has been described in around 30 countries around the world and is endemic in some parts of Pakistan. The fever is transmitted to humans by the bite of an infected tick either by direct contact with the blood or tissue via infected humans and livestock. We present here case of a 34-year-old Pak defense services officer who reported with nonspecific symptoms of high grade fever, myalgias and vomiting but rapidly deteriorated and developed bleeding diathesis. He was diagnosed to have CCHF and managed with Ribavirin, repeated transfusions and IV fluids with strict nursing barrier and use of Personal Protective Equipment (PPE). The patient recovered well. [ABSTRACT FROM AUTHOR]

Objectives: To see the Sofosbuvir Ribavirin combination therapy response in chronic HCV patients. Material and Methods: This study was conducted in private setup of Hepatitis clinics in collaboration with a private clinical laboratory of Peshawar,Pakistan. The patients were enrolled from July 2016 to December 2017.A total of 65 patients (54 naïve and 11 non- responder/relapser) were enrolled in this study. Age range was 18-70 years while mean age was 36 ± 2 years. For all of the subjects' biochemical profile and PCR tests were done at the start and end of therapy. All patients were given Direct acting antiviral drugs (DAA) drug for six months and after six month of therapy end of treatment response (ETR) was noted. Results: All the enrolled patients achieved 100% ETR. Alanine amino transferase (ALT) level improved in most of the patients (81%) while there was reduction in Hemoglobin level in 46.5% of the patients. Conclusions: Response rate in the current study is much higher as compared to previous studies conducted on Interferon based ribavairin therapy. [ABSTRACT FROM AUTHOR]

Background. The annual global deaths from viral hepatitis is 1.4 million. Pakistan has the second highest burden of hepatitis C in the world. There is dire need to evaluate the response of new direct acting antivirals for the treatment of hepatitis C patients in Pakistan. World Health Organization has developed a strategy to treat 80% of HCV patients by 2030. In Pakistan, HCV treatment rate is 1%. The aim of the study was to analyze the effect of Sofosbuvir plus Ribavirin therapy on HCV patients in Pakistan. Methods. An observational study was conducted at Fauji Foundation Hospital Rawalpindi from November-2016 to July-2017. All the drugs were administered according to the guidelines of Asia Pacific Association for the Study of Liver (APASL) for the treatment of HCV patients. A total 327 chronic HCV patients were enrolled in the study and 304 completed the treatment. Patients belonged to three different groups including treatment: Naïve patients (n = 107), Non-Responder patients (n = 126) and patients who relapsed to Interferon therapy (n = 71). All the patients were given Sofosbuvir plus Ribavirin therapy for 24 weeks and the early virological response (EVR) and end treatment response (ETR) was calculated. Different parameters including patient age, viral load, viral genotype, blood picture, ultrasound findings and liver function tests were also studied. Results. Out of 304 patients, 301 (99%) achieved EVR and 300 achieved ETR (98.7%). End treatment response was 95.6% in HCV genotype 1 and 98.9% in HCV genotype 3 patients. ETR was 99.06% in treatment Naïve, 99.20% in non-responders and 97.18% in previously relapsed patients. We did not find the association of any host and viral factor in the determination of EVR and ETR. Conclusion. The Sofosbuvir plus Ribavirin treatment is highly effective, safe and costeffective for the treatment of hepatitis C patients in Pakistan. [ABSTRACT FROM AUTHOR]

The most useful treatment for HCV infection worldwide is peg-interferon plus ribavirin, although the response varies from person to person. Hence, host genetics are significantly involved in the treatment response to HCV infection. The 2′-5′ oligoadenylate synthetase (OAS) is one of the most important components of the immune system having significant antiviral functions. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP) at the exon 7 splice acceptor site (SAS) of OAS1 to interferon-based therapy of HCV infection. OAS1 genotyping was performed in 140 HCV patients by restriction fragment length polymorphism polymerase chain reaction method (RFLP-PCR). These patients were enrolled for the study in 2010-2013. OAS1 SNP was also established in 120 healthy controls. Correlation of HCV genotypes, OAS1 SNP, and other factors with response to interferon therapy were statistically analyzed by SPSS 13 software. There were no significant differences in the distribution of OAS1 genotypes between healthy and patients subjects. The distribution of AG and AA genotypes of OAS1 genotypes between sustained virological responders (SVRs) and the non-responders (NRs) group were also comparable. However, Pearson chi square analysis indicated that the patients possessing a GG genotype of the OAS1 gene at exon 7 SAS demonstrated significantly positive association with treatment response to HCV infection ( p=0.039). This study determined that SNP at exon 7 SAS of OAS1 was significantly associated with response to interferon-based therapy of HCV infection in our population. [ABSTRACT FROM AUTHOR]

Background: Not enough data are available about the effectiveness of consensus interferon (CIFN) among HCV genotype 3 patients who failed to respond to pegylated interferon and ribavirin. Objectives: We aimed to assess the efficacy and safety of CIFN and ribavirin in non-responders and relapsers to pegylated interferon with ribavirin therapy. Patients and Methods: This open-label investigator-initiated study included 44 patients who received CIFN 15 μg /day plus ribavirin 800-1200 mg daily. In patients with an early virological response (EVR), the dose of CIFN was reduced to 15 μg thrice a week for further 36 weeks. Patients with delayed virological response continued to receive daily CIFN plus ribavirin to complete 48 weeks. The patients were considered “non-responders” if there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV RNA at 24 weeks. Results: Twenty-four patients (55%) were non-responders and 20 patients were relapsers to the previous treatment with pegylated interferon plus ribavirin (mean age 43.6 ± 9.4 years, males 25 (57%)). Nine patients were clinically cirrhotic (Child A). End of treatment virological response was achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred in 12 (27.3%). Out o f these 12 patients, eight were non-responders and four were relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosi s was associated with low SVR. Adverse events were fever, myalgia, anorexia, depression, and weight loss. Two patients received granulocyte colony stimulating factor for transient neutropenia. Seven patients were given erythropoietin to improve hemoglobin, and six were treated for mild depression. Two patients developed portosystemic encephalopathy. Conclusions: More than one-quarter of treatment-experienced patients with HCV genotype 3 achieved SVR after re-treatment with consensus interferon plus ribavirin. [ABSTRACT FROM AUTHOR]

Objective: To determine end treatment and sustained virological response to conventional interferons and ribavirin. Methodology: This descriptive study was conducted from January 2009 to September 2011 at DHQ hospital Dir, KPK, Pakistan. Three hundred and forty-seven patients of chronic hepatitis C aged 18 to 60 years were given conventional Interferons alpha 2a and Ribavirin for six months under Prime Minister Program for control of hepatitis. Results: Out of three hundred and forty seven patients three hundred and thirty nine patients completed the therapy. End treatment response was achieved in 229(67.5%) patients and sustained virological response was seen in 210(61.94%) patients. Conclusion: Combination of conventional interferon and ribavirin has a high sustained virological response with fewer side effects in our study. In resource depleted countries like Pakistan, conventional interferon alpha 2a and ribavirin combination therapy can be used as the first line treatment for non affording chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

About 10 million Pakistani population is infected with Hepatitis C virus (HCV). The prevalence is even more pronounced among high risk population. The commonest mode of transmission is the use of injections, unsterilized needles and contaminated instruments. Combination of standard interferon and ribavirin is still the first line therapy with sustained viral response (SVR) up to 40-50%. Pool of relapsers and non-responders is increasing in Pakistan and needs treatment with pegylated interferon plus ribavirin (peg IFN/RIB). Pegylated interferon has limited use due to being costly. Efficacy of pegylated interferon in genotype 3 is still debatable. HCV related end stage liver disease and hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in health care settings of Pakistan causing exponential burden on financial health care resources. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to examine the response of standard interferon therapy in chronic Hepatitis C Virus (HCV) patients of Khyber Pakhtunkhwa (KPK) province in Pakistan. The study involved 174 patients who were given standard interferon with ribavirin after confirmation of active HCV infection, and end of treatment virologic response (ETR) was examined. The study showed a high response rate of antiviral therapy against HCV infection in patients of the province.

Abstract: The effective standard therapeutic regimen for patients with chronic hepatitis C is pegylated interferon plus ribavirin. The efficacy of treatment in chronic hepatitis C is defined as absence of detectable virus at six months after treatment. Analysis of patient dependent and virus related factors that enable us to predict the response to antiviral treatment is very important. We prospectively studied 403 patients who received PEG-IFN alpha-2b 1.5μg/kg/body weight plus ribavirin. Treatment was administrated for 24 weeks and 48 weeks for hepatitis C virus (HCV) genotypes 3 and 1, respectively. Out of 403 treated patients, 301 patients (74.7%) showed a sustained virologic response (SVR). Seven variables (age, sex, ethnic group, pretreatment viral load, HCV genotyping and pretreatment ALT) were chosen as possible predictors of SVR and were analysed by means of univariable and multivariable logistic regression analysis. Five variables were statistically significant (p <0.005) on univariable analysis: age, ethnic group, pretreatment viral load, response rate at week 4, and HCV genotype. In multivariable analysis independent factors associated with SVR were low pretreatment viral load (1.97; 95%CI, 1.06–3.66; p =0.03) and attainment of rapid virological response (RVR) (7.19; 95%CI, 4.15–12.45; p <0.001). Our findings support the association between viral load and SVR to PEG-IFN-alpha-2b plus ribavirin therapy. No achievement of RVR is an unfavorable marker for SVR. These findings suggest that all patients considered for treatment should have quantification of serum HCV RNA levels. The result can be used to counsel patients on the likelihood of achieving SVR and may influence the patient''s decision on treatment. Future studies should confirm and explore this observation in other ethnic groups and in relation to HCV genotypes 1 and 3. [Copyright &y& Elsevier]

Background: Hepatitis C virus (HCV) is a major causative agent of liver associated diseases leading to the development of hepatocellular carcinoma (HCC) all over the world and genotype-3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current chemotherapy of interferon-α (IFN-α) and ribavirin against HCV infection alternative options are desperately needed out of which the recently discovered RNAi represent a powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process to silence virus infection or replication. HCV translation is mediated by a highly conserved internal ribosome entry site (IRES) within the 5'UTR region making it a relevant target for new drug development. Materials and methods: The present study was proposed to assess and explore the possibility of HCV silencing using siRNA targeting 5'UTR. For this analysis full length HCV 5'UTR of HCV-3a (pCR3.1/5'UTR) was tagged with GFP protein for in vitro analysis in Huh-7 cells. siRNA targeting 5'UTR were designed, and tested against constructed vector in Huh-7 cell line both at RNA and Protein levels. Furthermore, the effect of these siRNAs was confirmed in HCV-3a serum infected Huh-7 cell line. Results: The expression of 5'UTR-GFP was dramatically reduced both at mRNA and protein levels as compared with Mock transfected and control siRNAs treated cells using siRNAs against IRES of HCV-3a genotype. The potential of siRNAs specificity to inhibit HCV-3a replication in serum-infected Huh-7 cells was also investigated; upon treatment with siRNAs a significant decrease in HCV viral copy number and protein expression was observed. Conclusions: Overall, the present work of siRNAs against HCV 5'UTR inhibits HCV-3a expression and represents effective future therapeutic opportunities against HCV-3a genotype. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C is a major health problem affecting 270 million individuals in world including Pakistan. Current treatment regimen, interferon alpha and ribavirin only cure half of patients due to side effects and high cost. Results: In the present study Silybum marianum (Milk thistle) seeds were collected, extracted and analyzed against HCV 3a core gene by transiently transfecting the liver cells with HCV core plasmid. Our results demonstrated that Silymarin (SM) dose dependently inhibit the expression or function of HCV core gene at a non toxic concentration while the GAPDH remained constant. To identify the active ingredient, SM was fractioned by thin layer chromatography (TLC), column chromatography and HPLC. Purified fractions were tested for HCV core gene and western blotting results showed that two factions of SM (S1 and S2) inhibit HCV 3a core expression or function in liver cells Conclusion: Our results suggest SM and its fractions (S1 and S2) inhibit HCV core gene of 3a genotype and combination of SM and its fractions with interferon will be a better option to treat HCV infection. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis worldwide and its subtypes/genotypes are clinically important for clinical management and vaccine development. The present study describes frequency distribution of different HCV genotypes and their treatment status in HCV RNA positive patients from district Swat. A total of 185 HCV infected sera were analyzed by molecular genotyping assay. The most prevalent genotype was 3a (34.1%), followed by 2a (8.1%), 3b (7%) and 1a (5.4%). The samples found untypable by the present method of genotypes was 37.8% while, patients with mixed genotype infections were 7.6%. More than 80% of untypable cases were from those HCV patients who had received interferon plus ribavirin standard therapy in the past and either were non-responders and were relapsed thereafter or were under treatment. In conclusion, genotype 3a is the most prevalent HCV genotype in the region. A high prevalence rate of untypable genotypes is present in treated patients that need further investigation for the successful genotyping by developing new assays or using viral sequencing method. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever and dengue hemorrhagic fever are endemic in Pakistan. However, the overlap of geographic distribution and early clinical features between the two conditions make a reliable diagnosis difficult in the initial stage of illness. A 16-year-old boy presented with a history of hematemesis and high-grade fever. A preliminary diagnosis of dengue hemorrhagic fever was made and supportive treatment was instituted; however, the patient continued to deteriorate clinically. Dengue IgM antibody testing was negative on the third day of admission. Qualitative polymerase chain reaction test for Crimean-Congo hemorrhagic fever viral RNA was sent but the patient expired shortly after the results became available on the sixth day of admission. Considerable resources had to be expended on contact tracing and administration of ribavirin prophylaxis to all the health-care workers who had come in contact with the patient. It is crucial that Crimean-Congo hemorrhagic fever be recognized and treated at an early stage because of longer term financial and health implications for contacts such as health-care workers in the setting of a developing country. Increased surveillance of dengue and Crimean-Congo hemorrhagic fever cases is warranted for the derivation of reasonably reliable, cost-effective and prompt predictors of disease diagnosis. These predictors can help guide future decisions in the management of similar cases. Ultimately, such a strategy may translate into better cost containment in resource-poor settings. Institution of ribavirin prophylaxis in selected patients also merits consideration. [ABSTRACT FROM AUTHOR]

Summary: Objective:: To determine the peak time of outbreak of Crimean-Congo haemorrhagic fever (CCHF) and to highlight the disease-specific areas in the Balochistan province of Pakistan. Design:: A hospital-based case-series study. Place and Duration:: A five-year study was conducted by the Department of Pathology in collaboration with the Department of Medicine, Sandeman Provincial Teaching Hospital, Quetta, Balochistan, Pakistan, from 1 March 1997 to 28 February 2002. Patients and methods:: A total of 135 cases were included in the study based on a high index of suspicion of CCHF. The mean age was 33.5±18.7 years. Two sets of blood samples were drawn on admission; one set was sent for urgent routine investigations while the other was sent to CDC, Atlanta, USA, for confirmation. Results:: The study showed that CCHF was more common between March and May and again, between August and October, depicting a bi-annual surge. Out of 135 suspected cases, 83 (61.4%) were confirmed to have CCHF and were given platelet concentrate and ribavirin. It was observed that CCHF was more common in specific areas of the province. Conclusions:: It is essential to raise the level of knowledge regarding CCHF, especially in disease-specific areas, focussing on the peak outbreak periods. [Copyright &y& Elsevier]

Presents results of the study on the effectiveness of oral ribavirin for the treatment of Crimean-Congo haemorrhagic fever (CCHF). Case studies of three health workers infected with CCHF virus in Pakistan; Recovery and development of antibodies to the virus.

Background Treatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known. Methods We prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants. Results A total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure) Conclusion In a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The article focuses on the impact of Hepatitis C virus (HCV) on the public health in Pakistan. Topics discussed are challenge of Pakistan government to contain the infection despite treatment through oral Ribavirin mono therapy and free medical treatment, positive results after treatment with Directly Acting Antiviral (DAA) named Sovaldi, and efforts of Pakistan government for total elimination the virus and achieve the target prescribed by World Health Organization (WHO).

Hepatitis C Virus (HCV) infection is a major health concern worldwide. The presence of both HCV viral RNA and NS5A proteins in peripheral blood mononuclear cells (PBMCs) indicate the efficacy of the treatment during sustained virological response (SVR) and end of treatment response (ETR). The main objective of this study was to detect the absence or presence of HCV RNA and NS5A proteins in PBMCs. Blood samples were taken from selected patients (Islamabad, Pakistan) before treatment, at ETR, and during SVR. Two hundred HCV responders to pegylated IFN-α-2a plus ribavirin were selected. HCV RNA was extracted from the patients to determine the viral load by reverse transcription (RT)-polymerase chain reaction before treatment. Out of 200 patients, 152 (76%) and 48 (24%) achieved positive and negative ETR, respectively. Among ETR patients, 134 (88.2%) showed SVR, whereas 18 (11.8%) displayed relapse. The male to female ratio was 92:108 with mean age of 37.4 years. Among 152 ETR-positive patients, 29 (19%) patients' PBMCs were positive for HCV RNA and 27 (17.8%) were positive for NS55A proteins. Patients having HCV RNA in PBMCs showed higher relapse frequency compared with patients lacking it. Similarly, patients having NS5A protein showed significantly higher relapse frequency compared with patients lacking it. All PBMC-positive samples were of genotype 3a. In addition, patients with positive NS5A in their PBMCs showed greater risk of relapse compared with patients having HCV RNA. We conclude that the absence of both viral HCV and proteins can be used as an indicator for diagnosis of SVR in the future.

Summary: Background: Rapid virological response (RVR) is now thought to be the strongest predictor of sustained virological response (SVR) in hepatitis C virus (HCV) patients undergoing antiviral therapy. It can be used as a guide to individualize treatment duration. The aim of this study was to assess the role of RVR in tailoring the duration of treatment. Methods: Patients with HCV genotype 3 infections were enrolled and treated with pegylated interferon alfa-2a (PEG IFN alfa-2a) 180μg/week and ribavirin. HCV RNA was analyzed at weeks 4, 12, 16, and 24. Treatment duration was individualized on the basis of RVR. Patients who achieved RVR and who were aged ≤40 years with a body mass index (BMI) ≤27kg/m2 received 16 weeks of treatment (group A). Patients who achieved RVR and were aged >40 years with a BMI >27kg/m2, aged >40 years with a BMI ≤27kg/m2, and aged ≤40 years with a BMI >27kg/m2 received 24 weeks of treatment (group B). Patients who did not achieve RVR but who achieved an early virological response (EVR; HCV PCR-negative or ≥2 log drop in HCV RNA at week 12) were treated with 24 weeks of therapy (group C). Results: SVR was observed in 86% in group A, 82.2% in group B, and 46.8% in group C. A difference was observed in SVR for patients with and without RVR and receiving the standard duration of treatment (82.2% vs. 46.8%, p <0 .001). The results show that the rate of SVR is not inferior in those with RVR treated with 16 weeks of therapy compared to 24 weeks (86% vs. 82.2%, p =0.004). Conclusions: RVR is useful to individualize the duration of treatment and to predict the treatment outcome. A short treatment of 16 weeks is as effective as 24 weeks in HCV genotype 3 patients who achieve RVR, who have a low BMI, and are younger in age. [Copyright &y& Elsevier]

Summary: Crimean–Congo hemorrhagic fever (CCHF) is a deadly viral disease that is endemic in some parts of Pakistan. We report here the first ever case of CCHF from Abbottabad. The patient presented with abdominal pain, hematemesis and low platelets, and died within 24hours of admission. The diagnosis was confirmed by PCR for the CCHF virus. Because of the aggressive infection-control measures adopted, secondary and nosocomial spread was prevented. [Copyright &y& Elsevier]