Background: Various cytokine dynamics has been associated with chronic hepatitis C virus (HCV) infection. We hypothesized that cytokines have an important role in fibrosis development in HCV infection. Methods: All patients received liver biopsies to validate the severity of chronic hepatitis when enrolled in this study. Fluorescent Bead immunoassay was used to measure the following serum cytokine levels: Interferon γ, tumor necrosis factor α, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12. Various statistical analyses were used as appropriate. Results: From all the liver biopsy proven 92 HCV-infected patients, 49 (53.3%) were male, 23 (25%) patients had advanced (fibrosis grades 3-4) fibrosis, and the mean age of the study population was 51.9 ± 9.4 years. Elevation of baseline IL-4 level (>490 pg/mL) was associated with liver fibrosis grade by X2 test (odds ratio [OR] = 2.99; 95%, CI = 1.02-8.78; p = 0.042) and multivariate logistic regression (OR = 4.26; 95% CI = 1.13-16.02; p = 0.032). Also, IL-4 had strong diagnostic value in advanced liver fibrosis by using area under receiver operating characteristics curve analysis. Assessment of fibrosis score was consequently developed from our findings and compared with other noninvasive serum markers to assess liver fibrosis. Conclusion This study provides evidence that increased IL-4 expression predicted advanced liver fibrosis in treatment of HCV-infected patients.

Background: The most common clinical manifestation of HCV infection, which includes both hepatic and extrahepatic manifestations, is mixed cryoglobulinemia, which is characterized by the precipitation of certain proteins in the blood at temperatures below 37°C (in vitro), aggregation, and deposition in the walls of small and medium-sized vessels, causing vasculitis, which is clinically manifested by a triad of joint pain, fatigue, and rash on the soles of the feet. Cryoglobulin emia is commonly diagnosed in people with HCV infection, with a prevalence ranging from 10% to 70%. Vasculitis that occurs when cryoglobulinemia is detected mainly affects the small vessels of the skin, kidneys, and peripheral nerves, causing complications in other organ systems. Aim : To determine the prevalence of cryoglobulinemia in people with HCV infection, study it in relation to the stage of liver fibrosis, and determine its clinical relevance. Materials and Methods : 200 chronic HCV infected individuals were included in the study according to the inclusion and exclusion criteria. After obtaining informed consent from each participant, a questionnaire was used to collect infor mation, perform physical measurements, and collect peripheral blood samples. Complete blood count and biochemical tests (liver and kidney function) were performed. The degree of liver fibrosis was assessed non-invasively (APRI, FIB 4). The glomerular filtration rate was calculated electronically using the MDRD GFR Equation. Skin examination was performed to assess the presence of rash, ulcers, and scarring on the shins and ankles of cryoglobulinemia. To determine cryoglobulinemia, 8 ml of blood was collected in a tube without anticoagulant, and the sample was kept motionless for 1 hour at room temperature until clotting was complete. After centrifugation, the samples were separated and stored in a refrigerator at +4°C for 7 days, and then at room temperature for 30 minutes, the precipitate was detected. Results : A total of 200 people participated in the study, of which 71 were men (35.5%), the average age was 53.39±13.0. Cryoglobulinemia protein precipitates were determined in a total of 148 people, of which 50 were men (33.8%), the average age was 52.95±13.0. Cryoglobulinemia protein precipitates were detected in 89 people, or 60.1% of the study participants. Of the total study participants, 176 (88.0%) had chronic hepatitis C (CHC). Of these, 57 people had CHC with cryoglobulinemia. Comparing laboratory parameters, the mean GGT level in the cryoglobulinemia group was sta tistically significantly higher than in the non-cryoglobulinemia group (p=0.039). However, when laboratory parameters were grouped by increasing or decreasing, AST and ALT levels were significantly higher in the cryoglobulinemia group, indicating more hepatocellular damage (p<0.000). Increased creatinine levels may be associated with the risk of renal dysfunction. The FIB-4 index and APRI index showed a more severe degree of fibrosis in the cryoglobulinemia group (p<0.005; p<0.000). Univariate logistic regression analysis showed that age was associated with the occurrence of cryo globulinemia (OR=2.48; 95% CI:1.31–4.70; p=0.005). Platelet count had a statistically significant positive effect in mul tivariate analysis (OR=14.38; 95% CI:1.26–163.89; p=0.032). Conclusion The prevalence of cryoglobulinemia among HCV-infected patients was 60.1%, and older age and decreased platelet count among infected individuals were associated with the occurrence of cryoglobulinemia.