Standard Interferon Research Articles

Léčba pravé polycytemie

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by hematopoietic stem cell-derived clonal myeloproliferation resulting in erythrocytosis, leukocytosis and thrombocytosis. Survival is reduced compared with general population. Main reasons of death include thrombohemorrhagic complications, fibrotic progression and leuk-aemic transformation. Presence of Janus kinase (JAK2) gene mutations is a diagnostic marker and standard dia-gnostic criterion. World Health Organization 2016 diagnostic criteria focusing on hemoglobin levels, hematocrit, red cell mass and bone marrow morphology are mandatory. Therapeutic approach depends on stratification of patients according age and personal risk of thrombosis. Low-risk patients are treated first line with low-dose aspirin and phlebo-tomy. Cytoreduction is indicated in high-risk patients. Interferon-α has demonstrated efficacy in many clinical trials. Its pegylated form is well tolerated, enabling less frequent administration than standard interferon. Therefore it is therapy of choice based on Central European Myeloproliferative Neoplasm Organisation recommendation. Ropeginterferon α-2b has been shown to be more efficacious than hydroxyurea. Hydroxyurea is suspected of leukemogenic potential. JAK1/JAK2 inhibitor ruxolitinib is approved for hydroxyurea resistant/intolerant patients. Key words: diagnosis - polycythemia vera - therapy.

Recommendations for the diagnosis and treatment of patients with polycythaemia vera.

To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV). During meetings held from 2015 through 2017, CEMPO discussed PV and its treatment and recent data. PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression and leukaemic transformation. Presence of Janus kinase (JAK)-2 gene mutations is a diagnostic marker and standard diagnostic criterion. World Health Organization 2016 diagnostic criteria for PV, focusing on haemoglobin levels and bone marrow morphology, are mandatory. PV therapy aims at managing long-term risks of vascular complications and progression towards transformation to acute myeloid leukaemia and myelodysplastic syndrome. Risk stratification for thrombotic complications guides therapeutic decisions. Low-risk patients are treated first line with low-dose aspirin and phlebotomy. Cytoreduction is considered for low-risk (phlebotomy intolerance, severe/progressive symptoms, cardiovascular risk factors) and high-risk patients. Hydroxyurea is suspected of leukaemogenic potential. IFN-α has demonstrated efficacy in many clinical trials; its pegylated form is best tolerated, enabling less frequent administration than standard interferon. Ropeginterferon alfa-2b has been shown to be more efficacious than hydroxyurea. JAK1/JAK2 inhibitor ruxolitinib is approved for hydroxyurea resistant/intolerant patients. Greater understanding of PV is serving as a platform for new therapy development and treatment response predictors.

Treatment of Hepatitis C with Sofosbuvir in Combination with Ribavirin and Peg Interferon; a Prospective Study Highlighting the Sustained Virological Response

Objective: This study was intended to know the efficacy and safety of Sofobuvir in combination with Ribaviran and Peg Interferon on the basis of sustained virological response. Material and Methods: This was a prospective observational multicenter study with the use of non-probability convenient sampling technique. The duration of study was from January 2016 till July 2017. The study was conducted in lady reading hospital. The patients infected with HCV, belonging to both genders, and willing for treatment with standard interferon and Ribavirin were included in the study. The written consent was taken from all the patients with complete confidentiality of the data. HCV was diagnosed by detecting anti-HCV antibodies in serum with the help of Polymerase Chain Reaction (PCR). PCR was done at 12th week after the treatment and was classified as Sustained Virological Response (SVR). The therapy was categorized into dual containing Sofosbuvir and Ribavirin, triple containing Sofosbuvir, Ribavirin and Peg interferon. The dose of sofosbuvir, Ribavirin and Peg Interferon was 400 mg/OD, 1200 mg/OD and 180μcg/OD respectively. All data was entered and analyzed on SPSS version 20. Results: Total 386 patients were selected for the study including 172(45.5%) males and 214(54.5%) females with the male to female ratio of 1:1. They were divided into treatment naïve and experienced group with a frequency of 211(54.6%) and 175(45.4%). The frequency of genotypes of hepatitis C was found to be 4(1.9%), 1(0.5%), 2(0.9%), 1(0.5%), 178(84.3%), 20(9.5%), 3(1.4%) and 2(3.6%) for genotypes 1a, 2, 2a, 2b, 3, 3a, 3b and UT respectively in naïve patients and similarly it was 3(1.7%), 1(0.6%), 4(3.2%), 3(1.7%), 113(64.6), 44(25.2%), 5(2.9%) and 2(1.1%) respectively in experienced group. The overall SVR achieved regardless of the dual and triple therapy in naïve patients was 200(94.7%) and in treatment experienced patients were 144(82.3%). Conclusion: The Sofosbuvir is an effective drug for the achievement of sustained virological response in combination with Ribavirin and Peg Interferon. The uniformity in the high rates of achievement of SVR in dual and triple therapy suggests a powerful efficacy of Sofosbuvir in treating and eliminating the viral load in the patients infected with Hepatitis C Virus. Keywords: Hepatitis C; Sofosbuvir; Sustained virological response

Frequency of Hypothyroidism in Patients with Hepatitis C on Standard Interferon Therapy

Frequency of Hypothyroidism in Patients with Hepatitis C on Standard Interferon Therapy

ANTIVIRAL TREATMENT OF CHRONIC HEPATITISС: AVAILABLE RESULTS AND FUTURE PROSPECTS

Objective : to evaluate the effectiveness of two interferon (IFN)-based antiviral therapy of chronic hepatitis C (IFN/RBV or PEG-IFN/RBV)depending on HCV genotype, IL-28B gene mutations and to determinethe group of patients who need treatment with direct antiviral agents. Material and methods. The study involved 844 patients with chronic hepatitis C (60.6 % men; 51.9 % with genotype 1 virus) in two infectious diseases hospitals. 324 patients received treatment with standard interferon and ribavirin (IFN/RBV), 520 patients - with pegylated interferon and ribavirin (PEG-IFN/RBV). Polymerase chain reaction was applied to determinesingle nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 of IL-28B gene. Results. The effectiveness (sustained virologic response, SVR) of the scheme IFN/RBV in patients with HCV genotype 1 was 23.9 %, and of PEG-IFN/RBV - 48.4 %. The highest frequency rate of SVR was recorded in patients with CC variant of SNP rs12979860 - 73.3 and 82.1 % (for IFN/RBV and PEG-IFN/RBV schemes, respectively). Schemes IFN/RBV (SVR 70.8 %) and PEG-IFN/RBV (SVR 86.5 %) were highly effective for patients with HCV genotypes 2 and 3. The treatment was not effective in patients with genotype 1 HCV having gene IL-28B SNPs rs12979860 CT or TT and rs8099917 TG or GG and in patientsover 40. Conclusion. It is prospectiveto use non-IFN regimens based on direct-acting antiviral agents to treat patients with 1 HCV genotype with genotype CT/TT (rs12979860) and TG/GG (rs8099917), as well as those who did not respond previously to the antiviral treatment with PEG-IFN/RBV.The implementation of the non-IFN regimens should be accelerated by means of registration or development of production of generic drugs.

Comparing standard interferon and interferon conjugated with polyethylene glycol for treatment of patients chronically infected with hepatitis B virus infection

Background: The efficacy of interferon (IFN) has recently improved by the replacement of standard IFN by the type conjugated with polyethylene glycol IFN (PEG IFN). However, the superiority of PEG IFN regimen to therapy with standard IFN remains uncertain. Objectives: The present study aimed to assess and compare the efficacy of the two standard IFN and PEG IFN regimens for the treatment of patients chronically infected with hepatitis B virus (HBV) infection. Materials and Methods: The present study was conducted as a retrospective, cohort study assessing 138 consecutive patients diagnosed as a case infected chronically with HBV. The patients were randomly assigned to receive standard IFN regimen (n = 71) intravenously or PEG IFN regimen (n = 67) intravenously for total 24 weeks. All patients were monitored monthly regarding serum aminotransferase level and hepatitis B e antigen (HBe-Ag) positivity as the viral load. Results: Overall, 8.4% in standard IFN group and 10.4% in PEG IFN responded to the treatment regimens with no between-group difference (P = 0.715). The response to treatment protocols was independent to gender, age, and viral load. In addition, 66.7% responded to standard IFN regimen, and 42.9% responded to PEG IFN regimen were positive for HBe-Ag with no difference between the two protocols (P = 0.639). Adjusted for HBe-Ag positivity, the type of IFN used for the treatment of chronic hepatitis B infection could not be effective factor (odds ratio = 0.792, P = 0.690). Conclusion: Our study could not demonstrate the superiority of PEG IFN to standard IFN for treating chronic HBV infection.

Prevalence rate and prognostic value of the IL-28 gene polymorphism in hepatitis C patients in the Krasnodar territory

Objective. The study of the prevalence rate of the IL-28B genotype polymorphism in chronic hepatitis C (CHC) patients in the Krasnodar territory for the prediction of the effectiveness of various schemes of antiviral therapy. Materials and methods. There was executed the determination of single nucleotide polymorphisms (SNP) at loci rs8099917 and rs12979860 of the IL-28B gene in 833 CHC genotype 1 patients, aged of from 18 to 73 years, living in the Krasnodar Territory. In 260 cases the viral load has been determined. For genotyping IL-28B there was used the method of allele-specific PCR test system «AmpliSens Genoskrin IL28B-FL» in a amplifier with system of detection offluorescent signal in real-time mode “Rotor-Gene Q” (“Qiagen”, Germany). The investigation of the marker rs12979860 study was performed in combination with the marker rs8099917. Combinations of genotypic variants SNPIL-28B were compared with the rate of early virological response (EVR) and Sustained Virological Response (SVR) under antiviral therapy comprised of two components IFN/ ribavirin (20) andPEG-IFN/ribavirin (68 patients), as well as the "triple therapy": PEG-IFN/RBV/inhibitorsprotease 1 and 2 generations (16 cases). Results and discussion. In the Krasnodar territory in CHC genotype 1 patients there is prevailed heterozygous variant rs12979860 CTIL-28B (58.3%), potentially unfavorable in the prescription of "double" therapy. The detection rate of the protective allele CC is 2.1 times less often (27.7%). In the rs8099917 locus there is dominatedfavorable TTgenotype (53.4%), slightly exceeding the frequency of heterozygous risk genotype GT (41.2%). The frequency of combinations of various protective genotypes (CC+CT), less favorable (CT+TT), the most unfavorable for the prognosis (CT+GT) for two interleukin 28B gene loci is about the same accounting of from 26.3 to 32%. Patients with protective CC+TT alleles had the significantly higher viral load if compared with a group of patients with unfavorable TT+GG homozygotes. In the treatment of CHC patients with genotype CC+CT in investigated loci (rs12979860 and rs8099917) according to such schemes as IFN/RBV and Peg-IFN/RBV, EVR was observed in 100% and SvR - in 89.4-849% ofpatients respectively. The combination of CT+TT alleles of the IL28B gene significantly reduced the effectiveness of treatment of PEG-IFN/RBV to 50%; in this process a combination of CT+GT heterozygotes has the highest proportion while SVR does not exceed 33.3%."Triple" therapy with PEG-IFN/RBV/ protease inhibitors of 1st and 2nd generations eliminates the significance of the combination of unfavorable genotypes SNP of the interleukin 28B gene, allowing to achieve EVR in all the patients with the absence of protective alleles CC+TT, SVR - in 85.7% of cases. Conclusion. In choosing treatment regimens for CHC genotype 1 patients the differentiated approach is appropriate, with taking into account the favorable and unfavorable combinations of genotypic variants of the IL28B gene concerning rs12979860 and rs8099917. In patients with the presence ofprotective alleles CC+TT on these loci, a "double" combination therapy by as pegylated as well standard interferon preparations with ribavirin is highly effective and may be preferred; in the combination of less favorable alleles CT+TT, and particularly unfavorable heterozygotes CT+GT ofIL-28B gene, it is advisable to use a "triple" therapy with PEG-IFN/RBV/protease inhibitors of 1st and 2nd generations or non-interferon regimens. The study of the distribution of SNP genotypes of IL28B genes and their combinations in CHC patients C allowed to evaluate rationally the need of that cohort ofpatients for various, including expensive non-interferon, therapy schemes.

Interrelation between endogenous intoxication indicators and nitric oxide metabolites in the infectious process in chronic viral hepatitis C

Aim. To study dynamics and interrelation between final nitric oxide metabolites (nitrites) and endogenous intoxication index (medium mass molecules) in patients with chronic hepatitis C with the effect of antiviral therapy on them.Methods. The study included 99 patients with chronic hepatitis C. The combination therapy for 48 weeks in patients with genotype 1 chronic hepatitis C with pegylated interferon (peginterferon alfa-2a and alfa-2b) in combination with ribavirin and for 24 weeks with daily standard interferon alfa-2b administration in patients with virus genotypes 2 and 3 was conducted. The nitric oxide level was estimated by the content of the nearest metabolite (nitrite) in blood serum using the P.P. Golikov method. Medium mass molecules in the blood serum were determined by the N.I. Gabrielyan method.Results.In patients with chronic hepatitis C high values of nitrogen oxide metabolites and the medium mass molecules in the blood serum were revealed, whereas the level of nitroxidemia and endogenous intoxication by the values of medium mass molecules was associated with the viral replicative capacity value and alanine aminotransferase serum levels. Amid the combination antiviral therapy the nature of nitroxidergy changed with the normalization of nitrogen oxide indicators by 24 weeks and an increase to 48 weeks of treatment. There were significantly positive correlative relations between pronouncement of levels of nitric oxide metabolites and the medium mass molecules before the start of antiviral therapy (R=0.292629, pConclusion. Chronic hepatitis C promotes increase in nitrite ion content and medium mass molecules in the blood serum, their level is associated with virus replication activity and cytolysis severity; antiviral therapy has an effect on the level of endogenous intoxication with the normalization of content of the nitrite ions and medium mass molecules in blood serum by 24th week of treatment.

Promising Anti-Hepatitis C Virus Compounds from Natural Resources

Hepatitis C virus (HCV) infection is a major worldwide problem, which involves approximately 170 million people. High morbidity of patients is caused by chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma and other HCV-related diseases. The sustained virological response (SVR) has been markedly improved to be >90% by the current standard interferon (IFN)-free treatment regimens with a combination of direct-acting antiviral agents (DAAs) targeting the viral NS3 protease, NS5A multi-function protein and NS5B RNA-dependent RNA polymerase, compared with 50-70% of SVR rates achieved by the previous standard IFN-based treatment regimens with or without an NS3 protease inhibitor. However, the emergence of DAA-resistant HCV strains and the limited access to the DAAs due to their high cost could be major concerns. Also, the long-term prognosis of patients treated with DAAs, such as the possible development of hepatocellular carcinoma, still needs to be further evaluated. Natural resources are considered to be good candidates to develop anti-HCV agents. Here, we summarize anti-HCV compounds obtained from natural resources, including medicinal plant extracts, their isolated compounds and some of their derivatives that possess high antiviral potency against HCV.

A systematic review of community based hepatitis C treatment.

BackgroundHepatitis C virus (HCV) treatment uptake globally is low. A barrier to treatment is the necessity to attend specialists, usually in a tertiary hospital. We investigate the literature to assess the effect of providing HCV treatment in the community on treatment uptake and cure.MethodsThree databases were searched for studies that contained a comparison between HCV treatment uptake or sustained virologic response (SVR) in a community site and a tertiary site. Treatment was with standard interferon with or without ribavirin, or pegylated interferon and ribavirin. A narrative synthesis was conducted.ResultsThirteen studies fulfilled the inclusion criteria. Six studies measured treatment uptake; three demonstrated an increase in uptake at the community site, two demonstrated similar rates between sites and one demonstrated decreased uptake at the community site. Nine studies measured SVR; four demonstrated higher SVR rates in the community, four demonstrated similar SVR rates, and one demonstrated inferior SVR rates in the community compared to the tertiary site.ConclusionThe data available supports the efficacy of HCV treatment in the community, and the potential for community based treatment to increase treatment uptake. Whilst further studies are required, these findings highlight the potential benefit of providing community based HCV care – benefits that should be realised as interferon-free therapy become available.(PROSPERO registration number CRD42015025505).Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1548-5) contains supplementary material, which is available to authorized users.

Adverse effect profile of patients receiving anti viral treatment for chronic Hepatitis C virus infection

Chronic hepatitis C virus infection is present in 3 - 10 % of Pakistani population and genotype 3 is the most prevalent subtype in our patients. In a suitable candidate interferon along with Ribavirin is the main stay of treatment for these patients. These drugs have short as well as long term safety problem. Morbidity and frequency of discontinuation of therapy correlate directly with the frequency of adverse events while on treatment. Objectives: This observational study has been conducted to find out the adverse effect profile of anti viral treatment for our Chronic HCV patients. Material and method: From 1st March 2005 to 30th March 2005, 100 consecutive patients suffering from chronic HCV infection receiving standard interferon alpha 2 b and ribavirin were included. All of them were inquired on a questionnaire about the adverse events and then analyzed. Results and discussion: In as many as 65 % of the patients receiving anti viral treatment complained of an adverse event. The events were in the form of Flu like symptoms, abdominal pain, sleep disturbance, lack of appetite, dry cough and breathlessness, Depression, persistent fever, anemia, thrombocytopenia, neutropenia and skin rash. Conclusion: A high number of pts receiving anti viral treatment for ch. HCV infection suffer from adverse events.

PEDIATRIC CHRONIC VIRAL HEPATITIS – THERAPEUTIC CONSIDERATIONS

Chronic viral hepatitis is a public health issue both worldwide and in Romania, where the prevalence of the disease is still high. We present the available therapies used for chronic viral hepatitis B treatment in children, worldwide and in Romania, indications and contraindications of treatment, benefits and disadvantages for each class. The present paper reviews only the treatment options and not prophylactic measures for pediatric chronic viral hepatitis B. Currently, in Romania, standard Interferon is the treatment of choice. Entecavir is the only of the nucleotidic/nucleosidic analogues which is approved for children use, but not in those weighting less than 32.6 kg. Tenofovir, Adefovir and Lamivudine are not approved for pediatric chronic viral hepatitis B. Considering the fact that the disease progression is longer when the infection occurs earlier in life, efficient treatment is important for children with chronic viral hepatitis B. The availability of more treatment options provides a chance for patients who are nonresponsive to first line therapies.

Clinical efficacy of pegylated interferon in patients co-infected with HIV and HCV who failed standard interferon therapy

To investigate the efficacy and safety of pegylated interferon-alpha (PEG-INF-α) combined with ribavirin in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who failed prior standard interferon therapy. A prospective study was performed to analyze HCV RNA load, liver function, and CD4+ count at weeks 0 (baseline), 12, 24, and 48 of treatment and at 24 weeks after drug discontinuation in 20 patients co-infected with HIV and HCV who failed standard interferon therapy and were then treated with PEG-INF-αand ribavirin. Among the 20 patients, 14 were infected with HCV genotype 1b, 3 with HCV genotype 2a, and 3 failed sequencing. At baseline, the mean CD4(+)count, mean CD8(+)count, and mean CD4(+)/CD8(+)ratio were 406.45 ± 210.83 cells/ml, 1 076.45 ± 716.18 cells /ml, and 0.43 ± 0.17, respectively; the mean HCV RNA load was 6.01 ± 1.13 log10IU/ml; 12 patients (60%) had abnormal liver function. A total of 14 patients (70%) achieved complete early virologic response, 15 (75%) achieved end-of-treatment virologic response, 7 (35%) achieved sustained virologic response (SVR), and 8 (40%) experienced recurrence. The incidence rate of drug-related adverse events during the treatment was 50% (10/20); no serious adverse events occurred, and no patient withdrew from the treatment due to adverse events. At week 48, both CD4(+)and CD8(+)counts of all patients declined significantly compared with the baseline values (P= 0.001 and 0.001), but the CD4(+)/CD8(+)ratio increased significantly (P= 0.032). The SVR group had a significantly lower mean baseline HCV RNA load than the non-SVR group (4.95 ± 1.18 log10IU/ml vs 6.59 ± 0.53 log10IU/ml,t= 3.49,P= 0.009). In the patients co-infected with HIV and HCV who failed standard interferon therapy, PEG-INF-αcombined with ribavirin has good efficacy and safety, and the patients with a low baseline HCV RNA load are more likely to achieve SVR.

Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C

BackgroundThere have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations.ObjectiveTo determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population.DesignIn an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined.ResultsSustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002), estimated duration of infection (p=0.034) and HCV genotype (p<0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%).ConclusionsWe had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1.

Post HCV Infection Due to MX Gene Stimulation Produced Post Treatment with Imported and Locally Produced Egyptian Biosimilar IFN

Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK>Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity.One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias.Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 µg/week versus 90 µg/week) and PEG interferon alpha-2b (1 µg/kg versus 0.5 µg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences.Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second.No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.

Sustained virologic response to standard interferon or pegylated interferon and ribavirin in patients with hepatitis C virus genotype 5: systematic review and meta-analysis of ten studies and 423 patients.

Interferon (IFN)-free therapy has vastly improved therapeutic options for those with hepatitis C virus infection (HCV). However, the lack of data and the expense limit its use for lesser known genotypes such as HCV-5, especially in countries with financial limitations. Previous reports estimate sustained virologic response (SVR) rates in HCV-5 to be ~40-70%. Our goal was to estimate pooled SVR rates for HCV-5 treatment-naïve patients treated with IFN or peginterferon (PEG IFN) and ribavirin (RBV) combination therapy for 48 weeks. We conducted a literature search to identify articles with HCV-5 patients treated with IFN/PEG IFN + RBV. Pooled SVR rates were reported by random effects modeling with 95% confidence intervals. Heterogeneity was defined by the Cochrane Q-statistic p ≤ 0.05 and I(2) statistic ≥50%. A total of 423 patients from ten studies were included in the analysis. The pooled SVR rate for HCV-5 patients treated with IFN/PEG IFN + RBV for 48 weeks was 58.0% (CI 53.1%-62.7%). There was no evidence of heterogeneity (I(2) = 0, p = 0.61) or publication bias (Egger's test = 0.26). Pooled analysis of HCV-5 patients treated with PEG IFN + RBV was 55.0% (CI 49.4-61.5%). There was no evidence of heterogeneity (I(2) = 0.00, p = 0.75) or publication bias (Egger's test = 0.71). Combination therapy with IFN/PEG IFN + RBV had a pooled EVR of 90.2% (CI 76.8-96.2%). SVR for HCV-5 treated with combination therapy (IFN/PEG-IFN + RBV for 48 weeks) was approximately 60%. Current data are insufficient to evaluate variable duration of treatment (24 vs. 48 weeks), presence or absence of cirrhosis, effects of high versus low viral loads, or degree of fibrosis. The optimal treatment duration for HCV-5 patients with IFN-based combination remains to be established. Data and drug access are needed for treatment for HCV-5 in more resource-limited areas.

End-of-Treatment-Response in patients treated for hepatitis C virus with standard interferon and ribavirin based on viral load.

To determine the End-of-Treatment-Response (ETR) to standard interferon and ribavirin based regimen in patients of chronic hepatitis C and to compare the ETR response in low and high viral load groups. Descriptive study. Virology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2012 to May 2013. Patients with chronic hepatitis C virus infection were included in the study. Pre-treatment viral load was determined by RoboGene Quantification kit. Based on viral load, the 400 patients were divided into two equal groups of low viral load (< 800,000 IU/ml) and high viral load (> 800,000 IU/ml). The patients were treated with standard interferon alpha (3 million units subcutaneously thrice weekly) and ribavirin (10.6 mg/kg body weight) for 6 months. ETR was measured using Sacace Biotechnologies Qualitative kit. Chi-square test was used to compare the ETR in the two viral load groups. P-value < 0.05 was considered as significant. Out of 400 patients, 206 (51.5%) were males and 194 (48.5%) were females. Two hundred seventy (67.5%) patients achieved ETR and 130 (35.5%) failed to do so. In low viral load group, 145 (72.5%) patients achieved and 55 (27.5%) patients did not achieve ETR. In high viral load group, 123 (61.5%) patients achieved and 77 (38.5%) did not achieve ETR. The difference in ETR between low and high viral load groups was statistically significant (p=0.019). End-of-treatment-response in patients treated for hepatitis C virus with standard interferon and ribavirin was greater in patients with low viral load as compared to patients with high viral load.

Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review.

Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation.

Optimization of conditions for high-level expression and purification of human recombinant consensus interferon (rh-cIFN) and its characterization.

Recombinant human consensus interferon (rh-cIFN) is an artificially engineered interferon (IFN) developed by recombining and reordering the protein sequences that exist in standard IFN. This recombination resulted into a drug that has the potential to work better than natural, standard IFN. In this study, we described optimized conditions for high-level expression and recovery of biologically active consensus IFN from inclusion bodies (IBs). A synthetic gene coding 166 amino acids of consensus IFN was cloned under the T7 promoter. Escherichia coli strain BL21DE3Plys was used to transform expression construct. For high-level expression, shake-flask fermentation conditions were standardized. For isolation of IBs, the sonication method was optimized. A variety of chaotropic agents including guanidine hydrochloride, urea, SDS, and detergents were studied for solubilization of IBs. For renaturation of solubilized denatured protein by the dilution process, parameters of dilution factor, temperature, and l-arginine were optimized. A one-step chromatography method was developed for high-yield purification of consensus IFN. rh-cIFN was characterized by SDS-PAGE, Western blot, and high-performance liquid chromatography. Purified protein has a molecular weight of 19.5kDa and specific activity was 2.0 × 10(8) as determined by the cytopathic inhibition assay. This study concludes that by using optimized conditions, we obtained a yield of 100mg/L of biologically active rh-cIFN, which is highest ever reported according to available data.