The study was conducted at the Hepatitis Outpa- tient Clinic of Federal University of São Paulo. Pa- tients with chronic hepatitisC (positive for anti-HCV and HCV RNA) infected with geno- type 1 and treated with Peg-IFN and RBV bet- ween 2005 and 2010 were studied retrospectively. Criteria for inclusion in the study were age older than 18 years, a positive HCV RNA test (quantitati- ve detection by Taq-Man real-time PCR, with a de- tection limit of 50 IU/mL), histological grade of disease activity ≥ A2 and histological stage of fibro- sis ≥ F2 according to the Metavir score, and admi- nistration of at least one dose of Peg-IFN and RBV. Patients co-infected with HIV or HBV, patients with alcoholic liver disease, chronic kidney disease and decompensated cirrhosis, and organ transplant reci- pients were excluded.
This study identifies RBV and PI as the most likely drugs to cause AE. In this cohort, when a PI is part of the regimen, AE were three times more frequent, independently of RBV use. No patient treated with RBV and DAAs stopped medication due to AE . Three patients who discontinued treatment were getting a PI based therapy: 2 cases in combination with Peg-IFN and other development a HCC. Therefore, we did not find any association between PI-based therapies and discontinuations.
assess the safety and efficacy of combined therapy with pegylated interferon alfa-2a (Pegasys®, Roche, Basel, Switzerland) and ribavirin (Cope- gus®, Roche, Basel, Switzerland) inpatients with previously untreated chronic hepatitisC genotype 4. This observational study included pa- tients from 31 participating centers, with the ori- ginal intention of reaching 150 G4 participants. As no comparison was intended, no sample size calculation was performed. Patient enrollment started in February 2004 and the study ended in August 2005. Only patients between 18 and 65 years of age, with a histological hepatitis diagno- sis, HCV seropositive status, detectable HCV- RNA levels in serum (genotype 4) and aspartate transaminase levels higher than 1.5 times nor- mal values during at least 6 months were inclu- ded. Exclusion criteria were any other hepatic disorder, decompensated cirrhosis, viral co-infec- tions, immunodeficiency, drug abuse in the past 6 months before treatment onset, active alcoholism and severe comorbidities (respiratory or renal in- sufficiencies, epilepsy, depression, insomnia). Pregnant or lactating women and patients with abnormal laboratory findings suggesting anemia, altered coagulation or autoimmunity were exclu- ded. Informed, written consent was obtained from all participants, and studies were performed accor- ding to the World Medical Association Declaration of Helsinki. All procedures were approved by the ethics committee of the coordinating center. • Treatment and assessment of efficacy. All
Core tip: About 130-170 million people, is estimated to be infected with the hepatitisC virus. Chronic hepatitisC is one of the leading causes of liver-related death and in many countries it is the primary reason for having a liver transplant. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin (RBV). Since 2011 the accelerated incorporation of direct acting antiviral agents has created a new scenario: increasing the rates of sustained viral response, shorter therapies, less toxicity and regimens free of interferon and/or RBV and can even modify the natural history of the disease.
ed that HCV can impair the lipid cellular metabolism, through a modification in the responseto VLDL and LDL. In fact, Napolitano et al. demonstrated an impaired meta- bolic responseto VLDL and LDL isolated from patientsin- fected with HCV, with a slower VLDL catabolism, which can result in a higher VLDL-LDL switch in circulation. They also showed a higher LDL catabolism with subse- quent intracellular lipid accumulation leading to steatosis. The mechanism of response modulation to VLDL/LDL still needs to be explained, but it can be a consequence of a direct binding between HCV and lipoproteins or a modi- fication in their molecular composition. 86
Serum measurements of TSH, T4L (RR 0.8-1.9 ng/dL) were performed by a third- generation chemiluminescent immunometric assay (CLIA). Thyroid peroxidase antibody (TPOab) measurements were performed by third-generation immunometric assay (CLIA) RR < 22KIU/L. The analyzer used for the above measurements was IMMULITE-1000 Siemens Diagnostics. Blood glucose, uremia, blood creatinine and lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides) were assayed on automated analyzer, Dimensión RXL max Siemens.
modialysis patients monoinfected with HCV geno- types 1 and 2 showed higher SVR with pegylated interferon plus low-dose ribavirin than with IFN monotherapy. However, this results should be in- terpreted with caution in terms of extending these findings to hemodialysis patients worldwide be- cause of the high frequency of IL-28B T/T geno- type, lower mean body mass index of 22.5 kg/m², and lower rate of treatment discontinuation due to adverse events than in previous studies, where- fore all of these factors are associated with higher SVR rates. 39
molecular level, HCV decreases glucose transport into cells by down-regulating glucose transporter receptor (GLUT2). The virus also up-regulates expression of genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P-ase), which are integral en- zymes within the hepatic gluconeogenesis pathway. HCV also induces degradation of insulin receptor substrate (IRS), which blocks intracellular insulin signaling. Clear- ance of the virus has been shown to result in improved IR as measured by reduction in homeostasis model of assess- ment (HOMA) value, suggesting the virus itself plays a significant role in mediating IR. 1,13,15
Antiviral therapy inpatients suffering from chronic hepatitisC virus (HCV) infection and rare comorbidities cannot be easily started, as it can reduce the likelihood of a good therapeutic response with an increased frequency of side effects. We report two patients presenting unusual comorbidities associated with chronic Chepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic disease caused by a defect in colla- gen synthesis, the other one with the Charcot Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating peripheral neuropathy. Both patients were successfully treated with pegylated Interfe- ron (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement of a sustained viral response (SVR) and a low occurrence of adverse effects. Up to now there are no reports of patients suffering from chronic Chepatitis associated with these uncommon but severe comorbidities treated with antiviral therapy. In conclusion, in such clinical situations, anti-HCV therapy may be started and tailored, especially if the patient is highly motivated and if optimal predictors of response (i.e. young age, favourable genotype and low baseline viraemia) do exist.
Until a few years ago, standard-of-care treatment against hepatitisC virus (HCV) infection was dual therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV). Currently, this combination continues to be the backbone for some of the first-line recommended regimens. In addition, it is still recommended in settings where direct-acting antivirals (DAA) are not available due to financial restrictions . Rates of sustained virological response (SVR) to Peg-IFN plus RBV vary considerably according to host and virus-related parameters, such as IL28B genotype, grade of liver damage, baseline plasma HCV RNA concentration, and HCV genotype [2, 3].
HepatitisC infection is prevalent in candidates for and recipients of solid organ transplants. In the renal transplant population, HCV infection has been shown to decrease long-term patient and graft survival. The outcomes of HCV in recipients of other solid organ transplants are yet to be established and prospective studies will be needed in the future. In the absence of effective and safe antiviral treatment for HCV in- fection in renal, heart, and lung transplant recipients, the management of these patients remains a cha- llenge and has led to an increased focus on identifying and treating hepatitisCinpatients prior to transplantation. Interferon-based therapy for HCV prior transplantation appears to improve outcomes after transplantation. On the other hand, post-transplant interferon therapy is associated with an increased risk of graft rejection. Given the paucity of information on HCV treatmentin solid organ transplant reci- pients, there is a great need for large-scale, multi-centre randomized controlled trials to determine the optimal approach to HCV infection in this population. This article will summarize the current peer-re- viewed literature focusing on the efficacy of amantadine, ribavirin and both standard and pegylated inter- feron in the treatment of chronic hepatitisCin renal, transplant recipients.
significantly lower (p < 0.05) in thrombocytopenic pa- tients with viral cirrhosis when compared to both non thrombocytopenic and control groups. In contrast, TPO level was within the normal range in the patients with scistosomiasis either thrombocytopenic or not. while serum TAO activity was significantly lower (p < 0.05) in both thrombocytopenic and non thrombocy- topenic patients with schistosomiasis in comparison to control subjects with no significant difference between these two subgroups. Serum MDA concentration was increased significantly (p < 0.05) in all diseased groups when compared to controls with significant increase in thrombocytopenic patients as compared to non throm- bocytopenic. Conclusion: TPO hypoproduction played a role in the pathogenesis and treatment of viral cir- rhosis associated with thrombocytopenia. Also, total antioxidant activity and MDA are useful markers for monitoring patients with these chronic liver diseases. Key words: Cirrhosis, hepatitisC virus, schistosomia- sis, thrombopoietin, oxidative stress, lipid peroxida- tion, total antioxidant.
SUMMARY Background: Worldwide HCV studies have documented its large genetic variability; HCV has ma- jor genetic groups called genotypes that are designated from 1 to 6, as well as > 50 subtypes. This is very impor- tant considering that treatmentresponse varies accor- ding to genotype. The purpose of this trial was to ascer- tain prevalence of HCV genotypes in a group of patients from 10 states in Mexico. Methods: This study enrolled patients from 22 hospitals throughout the country. Pa- tients tested positive tohepatitisC antibody and genoty- ping was preformed by Lipa method. To carry out a com- parison, two regions were arbitrarily defined, the northern region embodied the cities of Culiacan, Torreón, Monterrey, Ciudad Obregón, and Tijuana, while the cen- tral-southern region embodied Mexico City, Guadalaja- ra, León, Puebla, and Veracruz. Results: The test was performed on a total of 421 patients. The most frequen- tly found genotype was genotype 1, present in 70.55% of cases. The majority (40.1%) corresponded to genotype 1b, 17.81% to 1a, and genotype 2a/2c (11.64%). A total of 29.4% of samples corresponded to genotypes non-1. Genotype 1 was found in 72.34 (northern region) and 70.03% (central-southern) of the two regions, and geno- types non-1 in 27.66 and 29.97%, respectively. Conclu- sions: We conclude that the most frequent genotype in Mexico is 1b, followed by 1a, and, in third place 1b1a, for a total of 70.55%; the remaining 29.45% had geno- types other than 1.
Introduction. The treatment of hepatitisC virus (HCV) genotype 1 with ribavirin (RBV) and pegylated-inter- feron alpha (peg-IFNα) provides a low-level sustained virological response (SVR). Single nucleotide polymor- phisms (SNPs) in the interleukin 28B (IL28B) gene have been identified as SVR predictors. Our aim was to establish an association between three IL28B SNPs (rs8099917, rs12979860, and rs8103142) and the peg-IFNα/RBV treatmentresponsein a Mexican population cohort with chronic HCV. Material and methods. A cohort study was performed with 83 chronic HCV patients at the Fundación Clínica Médica Sur in Mexico City. All patients were treated with peg-IFNα and RBV. The data were analyzed by logistic regression, with adjustments for age, gender, and viral genotype, to determine any associations between the SNPs and the treatmentresponse. Results. In the study group of 83 HCV patients, the main genotype was genotype 1 (70%, n = 58) and the overall SVR was 32.53% (n = 27). In the HCV-1 group, SVR was 27%, whereas SVR was 44% in the HCV-2 group. We found an association between rs12979860 CC and SVR in a codominant model (OR = 4.83, 95% CI = 1.12-20.8, P = 0.033). There was no statistically significant association between SVR and rs8099917 or rs8103142. rs12979860 polymorphisms of CC, CT, and TT, were present in 24%, 41%, and 35% of patients, respectively. Conclusion. A Mexican HCV-1-infected population treated with peg-IFNα and RVB had a low SVR rate, which was associated with the SNP rs12979860 (CC). SVR was not associated with the SNPs rs8099917 or rs8103142.
Given the ‘cons’ of liver biopsy, including the invasive character of the procedure, non-invasive tools have emerged to assess liver fibrosis . There are currently 6 available serological tests, being the FibroTest the most validated. Their specificity ranges from 41% to 91% and their sensitivity from 41% to 90%. The problem in HIV infection is that there are several markers that may be de- pendent on HIV-related factors: transaminase elevations may reflect drug hepatotoxicity, total bilirubin may be el- evated by certain antiretrovirals (i.e., indinavir and araza- navir), thrombocytopenia may be caused by HIV itself, and the MELD score system for transplant candidates has not been validated yet for HIV-infected patients. Never- theless, there are reports claiming the applicability of se- rum markers of fibrosis also in HIV-coinfected subjects. 50
The primary efficacy endpoint in the PROGRESS study was a SVR, defined as undetectable HCV RNA in the patient’s serum at the end of the untreated follow up period (study week 72). The secondary endpoints evaluated were the percentage of patients with undetectable HCV RNA levels at week 4, defi- ned as a rapid virological response (RVR), at week 12, defined as a complete early virological response (cEVR), and at week 48, defined as an end of treat- ment response (EOT). Patients with missing serum HCV RNA results at one of these time points were considered to be non-responders for the correspon- ding endpoint. The relapse rate was determined by the percentage of patients with an EOT response who reverted to an HCV RNA-positive status during their follow-up evaluation.
6 was 36 years. At diagnosis, the predominant clinical stage was compensated liver cirrhosis. When evaluated, five patients were at the chronic hepatitis stage, four of them had had a complete responsetotreatment. Thirteen patients were in the compensated liver cirrhosis stage, out of whom ten responded totreatment. Out of the six patients that were not compensated, none responded totreatment completely. Regarding the development of the disease, out of the 14 patients that had a complete responseto the treatment, ten remained in the same stage, four improved and none progressed to a more advanced stage of the illness. Conclusions. The responsetotreatmentinpatients with autoimmune hepatitis is strongly related to the non-progression of the disease.
Background and aim. DNA methylation plays a critical role in the control of important cellular processes. The present study assessed the impact of promoter methylation (PM) of some genes on the antiviral responseto antiviral therapy and it’s rela- tion to the presence of fibrosis in HCV-4 infected patients from Egypt. Material and methods. Clinical, laboratory and histo- pathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their responsetotreatment and the fibrosis status. The methylation profiles of the studied groups were determined using the following genes: APC, P14ARF, P73, DAPK, RASSF1A, and O6MGMT inpatients’ plasma. Re- sults. O6MGMT and P73 showed the highest methylation frequencies (64.2 and 50.9%) while P14 showed the lowest frequency (34%). Sustained virological response (SVR) was 54.7%with no significant difference in clinico-pathological or laboratory fea- tures between the studied groups. PM of O6MGM was significantly higher in non-responders (p value 0.045) while DAPK showed high methylation levels in responders with no significance (p value: 0.09) andPM of RASSF1A was significantly related to mild fibrosis (p value: 0.019). No significant relations were reported between PM of any of the studied genes and patients’ features. Conclusion. PM of some Tumor Suppressor genes increases in chronic active HCV-4. However, only 06MGMT can be used as a predictor of antiviral response and RASSF1A as a marker of marked fibrosis in this small set of patients. An exten- ded study, including more patients is required to validate the results of this preliminary study.
Some studies oriented toward establishing the action of the alternative therapies (AT), suggest reduction in pain and symptom intensity, as well as an earlier return to work activities inpatients with LDD. However, methodological limitations such as lack of uniformity in the defi nition of the disease, diffi culties when monitoring patients, conve- nience samples, heterogeneity in population groups, and problems to discriminate the effects of specifi c treatments were identifi ed (4). It is necessary to conduct a research to explore the effectiveness of alternative therapies in the treatment of patients with LDD, in order to provide evidence to support the use of these therapeutic methods, inpatients with poorresponseto a conventional medical treatment.
interferon alfa has the same sequence in the ISDR as gen- otype 1b. Patients with four or more amino acid substitu- tions in the ISDR (mutant type) exhibit full responses totreatment while those without substitutions (wild type) and 87% of those with 1–3 substitutions (intermediate type) do not respond totreatment. After treatment, the frequency of HCV quasispecies with wild-type ISDR se- quences increases, while that of quasispecies with amino acid substitutions in the ISDR decreases. European stud- ies have failed to replicate the results of many of these studies, most of which are of Japanese origin. 30 There are