الفهرس 
Epidemiology of HCV infectionOnly 14 pages are availabe for public view
 |  | from | 148 |  |  |
| | | from | 148 | | |
Abstract
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease (CID) and liver transplantation globally . HCV genotype 4 is responsible for approximately 13% of the cases of chronic HCV infection worldwide . Egypt has the highest prevalence of HCV infection worldwide (15%) , and genotype 4 represents 90% of all these cases , while the remaining 10% are due to HCV genotype 1 . Among patients with chronic hepatitis C , those with cirrhosis have the greatest clinical challenge. These patients need effective antiviral therapy to prevent progression to decompensation, end stage liver disease and hepatocellular carcinoma (HCC) . The primary goal of HCV therapy is to cure the infection which depends on developing sustained virological response (SVR). SVR means an undetectable HCV RNA level at 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion . The discovery of direct acting antiviral agents (DAAs) represented a revolution in the management of chronic HCV infection . Currently, oral combinations of these drugs are the standard of care for treating chronic HCV infection. Therefore, in this real-life cohort , the primary aim of the present study is to assess the efficacy and safety of combination of daclatasvir and sofosbuvir with or without ribavirin in the treatment of a group of Egyptian patients with chronic hepatitis C genotype 4 and cirrhosis. In the period from April 2017 to April 2018 a total of 50 Egyptian, cirrhotic patients with HCV genotype 4 infection which were the subject of the present study were selected and identified from Tanta Liver Center and outpatient clinic of Internal Medicine department Tanta University. All the study group were subjected to full history taking , complete clinical examination , laboratory investigations and abdominal US scan. The CTP score was estimated for all patients based on clinical , biochemical and US findings before treatment and 12 weeks after the end of treatment. All the study group were treated with a generic form of sofosbuvir 400 mg , daclatasvir 60 mg with or without weightbased ribavirin for only 12 weeks . 40 out of the 50 patients enrolled in the study , completed treatment , while the remaining 10 patients were lost for follow-up . Among the 40 patients who completed treatment ,34 were treatment-naïve and 6 were treatment- experienced. We monitored our treated patients by clinical , biochemical and US examination as well as HCV RNA by RT PCR before and 12 weeks after the end of treatment. Also , any treatment-related AEs as well as any complications were recorded . Majority of the study group (74%) were males , and 88% of them were from rural areas. A finding , that suggests a high prevalence of HCV infection among rural areas in Nile Delta . This may be attributed to the prevalence of schistosomiasis and consequently parenteral antischistosomal therapy in this endemic area as well as their cultural and social habits. Among our cohort , the most common risk factors for HCV infection are dental procedures , surgery and intrafamilial transmission being reported in 48% , 34% and 28% respectively. Concerning efficacy and antiviral response , the 12 weeks combination of SOF plus DCV achieved SVR in all treated patients (100%) whether treatment - naïve or experienced , with or without ribavirin. The mean pretreatment hemoglobin level was 13.31±1.5 gm/dl and 12 weeks after the end of treatment , the mean hemoglobin level decreased to 12.76±2 gm/dl. However, this decrease in hemoglobin level was statistically non – significant (P value >0.05). Conversely, the mean platelets count increased from 157525±80589 / mm3 before treatment to 167375±81870 /mm3, 12 weeks after the end of treatment. Also , this mild increase in mean platelets count 12 weeks after the end of treatment was statistically non - significant (P value >0.10). Meanwhile , a non - significant decrease was observed in the mean serum bilirubin level and INR 12 weeks after the end of treatment , compared to their level before treatment ( P value 0.10 , P value = 0.234, respectively ). Interestingly, a highly significant decrease in the level of transaminases was observed 12 weeks after the end of treatment , compared to the pretreatment level (P value<0.001). Additionally, a non - significant increase in serum albumin level was observed 12 weeks after treatment completion , compared to its level before treatment (P value >0.10). In view of these results , a non - significant improvement was observed in serum albumin, bilirubin and INR , while a highly significant improvement was observed in the level of transaminases 12 weeks after the end of treatment with SOF, DCV ± RBV. A finding that indicates the safety of this treatment modality regarding the synthetic functions of the liver. Moreover, the highly significant decrease in the level of transaminases 12 weeks after the end of treatment indicates marked improvement in the necroinflammatory process in the treated CHCV patients. Similarly , the current treatment with SOF, DCV ± RBV revealed non - significant changes in both hemoglobin and platelets count as compared to the baseline values. A finding that could be considered another advantage of this regimen besides its efficacy , especially in this group of cirrhotic patients in whom cytopenia is a common finding. Needless to say, the non - significant decrease in hemoglobin level observed 12 weeks after the end of treatment could be related to the use of ribavirin, however being non - significant , none of our treated patients required transfusion and/or discontinuation of RBV. Consequently , most of these cases were managed by reducing the RBV dose and in some cases addition of epoetin (EPO). Additionally, we monitored our treated patients by CTP score before and 12 weeks after the end of treatment. A non - significant decrease in the mean CTP score was observed in both Child ’s class A & B treated patients 12 weeks after the end of treatment ( P value = 0.628 , P value = 0.429 ) , a finding that indicates a marginal improvement in liver functions. Consequently , this could be considered an added safety advantage of this combination regarding liver functions . Surprisingly , all treatment-related AEs reported in our treated group were minor adverse events including , anaemia in 21 ( 52.5% ) , headache in 4 (10%) , fatigue in 4 (10%), dry cough in 3 (7.5%) and itching in only one patient (2.5%). Interestingly, none of our patients (0%) developed serious AEs such as (death , liver cell failure or hepatic encephalopathy) . A finding that confirms the safety and tolerability of this regimen in our treated cirrhotic CHCV patients. On further follow - up beyond the study period , one (2.5%) of our cohort with HCV GT4 cirrhotic patients developed HCC 3 months after achieving a SVR. A finding that clearly shows that in cirrhotic CHCV patients , HCC can develop despite achieving a SVR . Therefore, continous surveillance for HCC should be done in cirrhotics even after achieving a SVR.