الفهرس 
HCV INFECTIONOnly 14 pages are availabe for public view
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Abstract
Hepatic steatosis is frequent histological finding in patients with chronic HCV and it is one of the characteristic features of chronic hepatitis C. Steatosis affects chronic hepatitis C progression. Hepatic fibrosis is the most important factor for estimating clinical outcome and determining therapeutic strategy. The progression of chronic hepatitis C towards cirrhosis is relentless process that may evolve over period of decades.
This study was designed to investigate the impact of hepatic steatosis on the outcome of pegylated interferon and ribavirin combination therapy in patients with chronic hepatitis C genotype 4 (commonly present in Egyptian patients). It was conducted in between Tropical Medicine Department, Faculty of Medicine, Ain-ShamsUniversity and Kafr-SheikhLiverResearchCenter in the period from January 2010 to April 2011.
The current study included 148 patients who fulfilled the pre-designed inclusion criteria which were (adult patients ≥ 25 years and less than 60 years old with clinical, biochemical and ultra-sonographic criteria of chronic liver disease (Child A), non-diabetic, non-obese (BMI ≤30), positive serology for HCV antibody and HCV vireamia).
All the studied cases were subjected to the following; full history taking, thorough clinical examination, laboratory investigations [complete blood count (CBC), liver function tests including: serum AST, ALT, bilirubin, albumin, prothrombin time (PT) and INR. Hepatitis Viral markers (HBs Ag and HCV Ab, Quantitative HCV-RNA by PCR before treatment and at week 4, 12, 24 and 48, then at 24 weeks after end of treatment) as well as glucose profile and lipid profile. Abdominal ultrasound, liver biopsy and histopathological examination also were done for all cases.
According to the histopathological grade of steatosis, enrolled patients were classified into two groups:
group A: This group included 69 patients (48 men and 21 women; mean age of 40.97.4 years) with liver steatosis < 30%.
group B: This group included 79 patients (57 men and 22 women; mean age of 40.54 7.4 years) with liver steatosis > 30%.
There were no statistically significant differences in ageor gender between the two groups, but there is nevertheless a significant (P=0.0447) difference in BMI. Baseline ALT, AST and bilirubin levels, hemoglobin, RBCs, WBCs and platelet counts were comparable between the two groups. However, significant differences in the lipid profile (triglycerides and cholesterol levels) and blood sugar level were observed. An earlier normalization of ALT levels was observed in patients who attained sustained virologic response.
One of the featuresthat was seen in a majority of patients in this study was the presence of steatosis which varied from mild to severe and withno associated sinusoidal fibrosis. Variable degrees of steatosis were detected in the liver biopsies of 142 patients (95.9%) whileno detectable steatosis was detected in six patients. Among the 142 patients with steatosis, sixty-three patients either had steatosis less than 30% (63 patients, 42.5%), 45 patients (30.4%) had moderate steatosis ranging between 30-60% and 34 patients (22.9%) had extensive steatosis exceeding 60%. In 40 patients, steatosis was not associated with sinusoidal fibrosis.
Of the 148 enrolled patients, 117 patients (79.5%) achieved undetectable HCV-RNA or had > 2 log decline in HCV RNA after 12 weeks of therapy,while 31 patients were considered non-responders (showed no or minimal change in HCV RNA levels at week 12) and discontinued therapy. Of the 117 patients, 46 patients (39.3%) attained RVR (undetectable HCV-RNA after 4 weeks of therapy), 37 patients (31.6%) had undetectable HCV RNA at week 12 (cEVR), while 34 patients (29%) had > 2 log decline in HCV RNA (pEVR).
In an intent to treat analysis, 94 of 148 patients (63.5%) achieved undetectable HCV-RNA after 24 weeks of therapy completion (SVR). SVR was achieved in 44 of 46 patients (95.5%) with RVR, 32 of 37 (86.5%) with undetectable HCV RNA at week 12 (cEVR), and 18 of 34 (52.9%) in patients with partial early virologic response (pEVR) with an overall SVR rate of 63.5%.
There isa strong association between the degree of liver steatosis and fibrosis staging. Although patients with high grading scores tended to have more steatosis; there is a statistical significant correlation between the degree of steatosis and the necro-inflammatory grade.
We identified certain predictors of SVR, regardless of group assignment, before and after adjustment for other baseline factors. After controlling for other predictors, for each decade difference in age, those who were younger had higher odds of SVR [odds ratio (OR): 1.39; 95% confidence interval (CI): (1.02–1.89); P = 0.036]; females were more likely to attain SVR than males (OR: 2.08; 95% CI: 1.28–3.37; P = 0.003).
An association was observed between serum triglyceride levels and SVR as well as serum cholesterol levels and SVR. Both factors were considered statistically significant. Patients with normal cholesterol [odds ratio (OR): 2.01; 95% confidence interval (CI): (1.32–3.76); P= 0.042]; and/or normal triglyceride levels (OR: 2.16; 95% CI: 1.48–3.61; P = 0.002.
Baseline HCV-RNA was also found to influence SVR. The odds of attaining SVR were reduced with each log10 increase in baseline HCV RNA (OR: 0.01; 95% CI: 0.003–0.12; P = 0.0007).
The histologic grade was a strong predictor of SVR. Patients with lower degrees of steatosis were more likely to achieve SVR (OR: 2.17; 95% CI: 1.09–4.55; P = 0.029). Patients with a no or < than 30% steatosis in liver biopsies had 616 times the likelihood of achieving SVR than those with stage 2, 3, or 4 (P = 0.006). In this population, age was not a significant predictor of SVR (P = 0.12).
Finally and according to our results hepatic steatosis and obesity were predictors of poor response to pegylated IFN and ribavirin therapy in CHC genotype 4.So reduction of the weight before treatment is an important to improve sustained response rates. The evaluation of hepatic steatosis is not only useful for prediction of treatment outcome, but also important for investigation of new approaches toward overcoming the IFN resistance in patients with chronic hepatitis C.