الفهرس 
Epidemiology of HCVOnly 14 pages are availabe for public view
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Abstract
SUMMARY & conclusion
HCV is a major cause of chronic liver disease [Marcellin P, et al., 2002]. The estimates of disease burden showed an increase in seroprevalence over the last 15 years by 2.8%, equating to >185 million infections worldwide [Mohd HK., et al., 2013].
Hepatitis C is the most common cause of chronic liver diseases in Egypt. Egypt has the highest worldwide seroprevalence, estimated among the 15–59 years age group, to be 14.7% [Mohamoud YA, et al., 2013] Despite aggressive programs toward education, care, and treatment over the last 10 years, Egypt faces the largest burden of HCV infection in the world, predominantly genotype 4 [CDC 2012].
New regimens involving direct-acting antiviral agents (DAAs) have recently been approved for the treatment of genotype 4 HCV. These regimens appear to offer improved rates of SVR in treatment-naive and previously treated patients with genotype 4 HCV; however, few patients have received these regimens and data concerning efficacy and safety are sparse [Muir AJ, 2014].
One of the approved DAAs indicated for the treatment of genotype 4 HCV is sofosbuvir, an oral, HCV-specific NS5B nucleotide polymerase inhibitor with demonstrated clinical efficacy in patients with genotype 1 to 6 HCV [Lawitz E et al., 2013 & Jacobson IM et al., 2013].
This study was carried out at tropical medicine department outpatient clinic at Tanta university hospitals during the period between October 2014 and October 2017. Three hundred and twenty four (324) patients were diagnosed with chronic HCV, received treatment in the form of sofosbuvir-containing regimens and followed up during and after the end of the therapy for 3-6 months.In our study, the mean age of our patients was (55.864 ± 9.738) years old, the majority (264) (81.48 %) of patients aged less than 65 years old while only (18.52 %) were equal to or more than 65 years old (60). Males represent (51.85 %) (168) of the studied patients where females represent (48.15 %) (156) of the patients. The majority of patients were cirrhotic by ultrasound (55.56 %).
According to liver stiffness measurements by fibroscan, we found that only 4.94 % of patients were F3 with sever fibrosis while F4 with cirrhosis constituted the majority of patients, 65.43 %, F0 was detected in (3.7 %), F1 in (12.35 %), F2 in (13.58 %) of patients. In this study, the majority of patients were treatment-naive (88.89 %) while treatment- experienced patients represented only (11.11 %).
Our study included patients treated with sofosbuvir+IFN+ ribavirin (6.17 %), sofosbuvir plus ribavirin (41.98 %), sofosbuvir plus daclatsavir (30.86 %), sofosbuvir + simeprevir (3.70%) and sofosbuvir +daclatasvir + RBV. (17.28 %).
In our study, patients reported some side effects while on therapy, mostly less severe and managed easily & appropriately. Fatigue and anemia were the most common adverse effects reported (66.66 % for both).
In our study, 33.33 % of patients suffered from anemia mainly due to ribavirin-induced hemolytic anemia especially if ribavirin was given for 24 weeks and the mean hemoglobin level was decreased significantly from (12.059 ±1.707) gm/dl pre- treatment to (10.668 ± 1.113) gm/dl at 24 weeks of starting treatment.
That anemia was managed by ribavirin dose reductions when hemoglobin level reached 10 gm/dl and ribavirin stoppage if Hb. level reached 8.5 gm or less.
Marked hepatic decompensation with jaundice and hematemesis occurred at 4 weeks of starting treatment and leaded to death of 8 patients (2.47 %) while HCC development occurred also in 8 patients 8-12 weeks after starting treatment leaded to virologic failure and positive HCV PCR while on treatment.
In our study, the mean serum albumin was (3.603±0616) gm %, the mean serum bilirubin level was (1.462 ± 0.876) mg/dl, the mean Prothrombin activity of our patients was (77.494 ± 17.177) %, the mean serum ALT was high i.e. (52.023 ± 30.000) IU/L, Serial measurements revealed highly statistically significant reductions in its level while on treatment, meaning that high abnormal values were normalized by anti HCV treatment, mean serum AST was (66.369 ± 40.655) IU/L which is also relatively high, Serial measurements revealed also, highly statistically significant reductions in its level occurred while patients were on treatment, meaning that high abnormal values were also normalized by anti HCV treatment.
We noticed that, there was a remarkable improvement of the liver functions especially, liver enzymes, total bilirubin and Prothrombin activity with the administration of anti-HCV treatments. Also, the mean serum alpha-feto protein was (37.975 ± 151.455) ng/ml and serial measurements revealed a highly statistically significant reduction in its level at 24 weeks, meaning that high values were normalized by anti HCV treatment.
In our study, overall SVR 12 was achieved in (92.11 %) of patients, while non-SVR 12 was found only (7.89%). As regard treatment regimens were given, all patients received IFN.based therapy, sofosbuvir + Simeprevir and sofosbuvir + daclatasvir showed 100 % response (i.e.: SVR 12) while only 83.87 % of patients received sofosbuvir + ribavirin achieved SVR 12 and 92.31 % of patients received sofosbuvir + daclatasvir + ribavirin achieved SVR 12, and these results were statistically highly significant.
It was found that all patients with liver stiffness stages F0, F1, F2, and F3 achieved 100 % response (i.e.: SVR 12), Among cirrhotic patient, our result of SVR 12 was (87.5%), So, among patients who were non responders i.e. ”non-SVR 12”, our study showed that 100 % of whom, were cirrhotic and all non-cirrhotic patients were responders to different modalities of ant –HCV treatment regimens.
Regarding our study, we observed that 93.55 % of patients aged less than 65 years old achieved SVR 12 vs. 85.71 % in patients aged more than 65 years old, also, SVR 12 was achieved in only 86.49 % of males vs. 97.44 % of female patients.
Similarly, SVR 12 was more associated with serum albumin ≥ (3.662 ± 0.627) gm/dl & total bilirubin ≤ (1.370 ± 0.848) mg/dl. It was found that 92.65 % of treatment-naïve patients achieved SVR 12 vs. (85.71%) in treatment- experienced patients and only 75 % of interferon- experienced patients achieved SVR 12, while 100 % of patients with DAAs- experience did so, and these results were statistically significant.
So, predictors of response concluded from our study, were female patient, aged less than 65 years old, treatment-naive, with lower liver stiffness values, higher serum albumin and a lower total bilirubin level while baseline viral load had no impact on the response to the therapy. And, difficult to treat patients could be described as being male, aged 65 years old or more, interferon-experienced, cirrhotic with lower serum albumin and a higher total bilirubin level.
Our study reflects the “real-life” situation in many large referral centers and provides important learning points in these “difficult-to treat” patients with DAAs combinations.