الفهرس 
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Abstract
The role of ribavirin is still highly debatable among hepatologists with the allegations of a high unsafety profiles. Further studies better judging ribavirin are still mandated especially in a country cursed with the highest HCV burden all-over the world like Egypt.
The present study was intended to evaluate the role of ribavirin in the era of all oral DAAs therapies of CHC Egyptian patients.
The primary efficacy endpoint of our study was to achieve sustained virological response which is defined as undetectable HCV RNA 12 weeks after the end of therapy or failure of treatment due to non-response or occurrence of side effects.
In this case control study, we enrolled 847 CHC patients treated with DAAs with or without ribavirin divided into five groups : Non-cirrhotic patients, Patients with compensated cirrhosis, Patients with decompensated liver cirrhosis, Patients treated with DAAs post liver transplantation and treatment experienced patients.
All patients’ demographics, laboratory characteristics, and abdominal ultrasound were evaluated at baseline, week 4 during treatment and at week 12 (end of treatment).
Patients proved to have other chronic liver diseases e.g. Patients with HBV, HIV co-infections and other causes that contribute to liver diseases e.g. autoimmune hepatitis, Wilson disease and Hemochromatosis, were excluded. Furthermore, patients with Hepatocellular Carcinoma (HCC) and Pregnant women or those who are unwilling to comply with adequate contraception were also excluded.
All patients underwent through history taking, complete physical examination, liver function tests, renal function tests, CBC and serum HCV RNA count by PCR done before treatment, then 12 weeks after treatment.
Statistical analysis of the epidemiological, demographic, and laboratory data of the five patient groups had cleared the following:
1) Non-cirrhotic group: - No statistically significant difference between ribavirin and non-ribavirin regimens regarding SVR. - Significant improvement of ALT, AST, Serum bilirubin, Serum albumin, Platelet count and INR between start and end of treatment among different treatment regimens without significant difference between ribavirin and non-ribavirin regimens. - Only 7 patients experienced Anemia related to ribavirin usage, had to gradually decrease ribavirin dose and did not need to stop ribavirin without affecting treatment response and SVR. - There was no significant correlation between ribavirin usage and SVR. 2) Compensated cirrhosis group : - No statistically significant difference between ribavirin and non-ribavirin regimens regarding SVR. - Significant improvement of ALT, AST, Serum bilirubin, Serum albumin, Platelet count and INR between start and end of treatment among different treatment regimens without significant difference between ribavirin and non-ribavirin regimens. - Only 6 patients experienced adverse events. 4 patients experienced anemia related to ribavirin usage, had to gradually decrease ribavirin dose and did not need to stop ribavirin without affecting treatment response and
SVR. 2 patients developed decompensation in the form of jaundice and ascites (one during treatment and had to stop at 4th week while the other one achieved SVR12 and developed jaundice and decompensation 4 weeks after end of therapy. - There was no significant correlation between ribavirin usage and SVR. 3) Decompensated cirrhosis group : - No statistically significant difference between ribavirin and non-ribavirin regimens regarding SVR except for patients with MELD > 18 , Total number of patients were seven patients , only one of them received RBV regimen (SOF/DAC/RBV) and achieved SVR and the other six patients received RBV free regimens (SOF/DAC) with five patients achieving SVR and one patient didn’t achieve SVR. Therefore, Further studies are needed for better judgement of ribavirin use in decompensated cirrhosis patients with MELD > 18.
-Significant improvement of ALT, AST, Serum bilirubin, Serum albumin, Platelet count and INR between start and end of treatment among different treatment regimens without significant difference between ribavirin and non-ribavirin regimens. - Only 8 patients experienced Anemia related to ribavirin usage, had to gradually decrease ribavirin dose and did not need to stop ribavirin without affecting treatment response and SVR. - There was no significant correlation between ribavirin usage and SVR. 4) Post liver transplantation : - No statistically significant difference between ribavirin and non-ribavirin regimens regarding SVR. - Significant improvement of ALT, AST, Serum bilirubin, Serum albumin, Platelet count and INR between start and end of treatment among different treatment regimens without significant difference between ribavirin and
non-ribavirin regimens. - Only 4 patients experienced Anemia related to ribavirin usage, had to gradually decrease ribavirin dose and did not need to stop ribavirin without affecting treatment response and SVR. - There was no significant correlation between ribavirin usage and SVR. 5) Treatment experienced patients : - There was statistical significant difference between ribavirin and non-ribavirin DAAs treated patients regarding SVR (SVR12 rate was 96.8 % , 85 % in ribavirin and non-ribavirin regimens respectively) with ribavirin group showing higher SVR rate. - Ribavirin regimens showed statistically significant higher SVR rate with treatment experienced cirrhotic patients and no significant difference between ribavirin and non-ribavirin regimens among non-cirrhotic patients.Also ribavirin regimens showed statistically significant lower relapse rate. - Significant improvement of ALT, AST, Serum bilirubin, Serum albumin, Platelet count and INR between start and end of treatment among different treatment regimens without significant difference between ribavirin and non-ribavirin regimens. - Only 16 patients experienced Anemia related to ribavirin usage, had to gradually decrease ribavirin dose and did not need to stop ribavirin without affecting treatment response and SVR. - There was significant correlation between ribavirin usage and SVR with statistically significant higher SVR with ribavirin usage. All groups : - There was no statistical significant difference between ribavirin and non-ribavirin DAAs treated patients regarding SVR (Overall SVR12 rate of 97.6 % with 97.2 % , 97.8 % in ribavirin and non-ribavirin regimens
respectively) with high SVR in both groups except for treatment experienced patients, there was statistically significant difference between ribavirin and non-ribavirin DAAs treated patients regarding SVR (SVR12 rate was 96.8 %, 85 % in ribavirin and non-ribavirin regimens respectively) with ribavirin group more significant with a P value 0.001. Also, regarding treatment duration, SVR12 rate did not differ as it was 97.2 % , 94.2 % for those who received ribavirin regimens for 12 weeks and those who received non-ribavirin regimens for 24 weeks respectively. This allows for shortening of therapy using ribavirin/DAA combination without affecting SVR. - Overall, we noticed improvement of liver function of our studied patients following DAA/Ribavirin administration, particularly liver enzymes (ALT, AST), serum albumin level , serum bilirubin level and INR value with no statistically significant difference between ribavirin and non-ribavirin regimens. - In our study, we noticed that adding ribavirin to DAA regimens is generally associated with modest adverse events particularly anemia than ribavirin free regimens, this did not appear to affect patients ability to complete treatment and also did not affect treatment response and SVR.
There was no notable serious or life threatening drug related adverse events. None of our patients were lost during treatment. Only one patient with compensated cirrhosis stopped treatment at 4th week of treatment due to hepatic decompensation in the form of jaundice and ascites (patient received SOF/DAC/RBV regimen).
Moreover, 37 patients developed anemia. All of them were among ribavirin regimens (8.5 % of ribavirin regimen group) and had to gradually decrease ribavirin dose without affecting treatment response and SVR).
patients experienced fatigue (5.5 % of our studied patients). 22 patients experienced headache (3.8 % of our studied patients).
2 patients developed decompensation and jaundice (0.3 % of ribavirin regimen group) (one during treatment and had to stop at 4th week while the other one achieved SVR12 and developed jaundice and decompensation 4 weeks after end of therapy. - Platelet count, ALT, AST, albumin, INR, and bilirubin showed significant correlation with treatment outcome and SVR. - Ribavirin usage did not affect SVR among different treatment groups except for treatment experienced group.