الفهرس 
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Abstract
HCV infection is one of the main causes of chronic liver disease worldwide and it is the leading cause of hepatic cirrhosis in Egypt. HCV-related decompensated cirrhosis has become the commonest indication for LT, but availability of HCV DAAs has undergone a paradigm shift in treatment of decompensated cirrhosis. Achieving SVR is associated with a considerable improvement in CTP and MELD scores. However, improvement in MELD score biochemical parameters may not be enough to remove some individuals from the MELD purgatory list. So, the aim of this study was to evaluate the pretreatment predictors associated with improvement in patients with HCV related decompensated cirrhosis after DAAs and to evaluate the efficacy and safety of these drugs in these decompensated patients. This study was a prospective cohort study that included 246 Egyptian HCV related CTP B cirrhotic patients. All patients had code number to insure the privacy of patients. The study started from April 2019 to April 2021, with only 213 participants completed to the end of the study. CTP B (B7 & B8) cirrhotic patients and treatment-naïve with positive HCV RNA who aged more than 18 years were included in the study. CTP C cirrhosis, pregnant females, HCC except 6-12 months after curative intervention, extra-hepatic malignancy except after 2 years of disease-free interval except in cases of lymphomas and chronic lymphocytic leukemia, HBV or HIV co-infection, platelets <50,000/mm3, Hb < 10 gm/dl, ALT or AST ≥ 5 ULN, Hb A1c > 9 % and eGFR ≤ 30 mL/min/1.73 m2 were the exclusion criteria. Poly medicated patients were on their routine treatments during the study as anti-diabetic, anti-hypertensive, thyroid diseases therapies, also diuretics and beta-blockers were received for treatment of ascites and portal hypertension respectively. All patients after informed consent were subjected to full history taking with special emphasis on symptoms of hepatic decompensation as history of ascites, HE, pedal edema, history of upper gastrointestinal bleeding as hematemesis & melena then complete clinical examination had been done. Baseline laboratory investigations were performed as complete blood count, liver enzymes and function tests, coagulation profile (INR), serum creatinine, fasting blood sugar, HbA1c, serum AFP, virology tests (PCR of HCV RNA, HBs Ag, HBc Ab & HIV Ab), BMI with estimation of dry body weight in hypervolemic patients, pregnancy test in female patients in childbearing period. from the previous laboratory investigations, three baseline scores were calculated as CTP, MELD and BE3A scores. CTP score was calculated by simple numerical summation of HE, ascites, albumin, bilirubin and INR, MELD score was calculated from serum bilirubin, serum creatinine and INR, and BE3A score was calculated by simple numerical summation of BMI, encephalopathy, ascites, ALT, and albumin. Baseline radiological investigations were done as abdominal US for liver, spleen & ascites and triple-phasic abdominal CT in suspicion of HCC, echocardiography& ECG in elder patients above 65 years or if needed below this age and lastly upper endoscopy for screening and management of varices. Clinical and laboratory follow-up was done from the start of DAAs until 6 months after achieving SVR. During DAAs plus RBV, 2 weeks follow-up was done by ALT, AST, CBC & bilirubin to detect any adverse effects and modify RBV dose according to tolerability. During DAAs without RBV, monthly follow-up was done by ALT, AST & CBC. At 36 weeks of treatment start, follow-up was done by (serum bilirubin, serum albumin, INR & abdominal US) for calculation of CTP score to measure the validity of the BE3A score in prediction of improvement to compensated CTP A after DAAs in CTP B cirrhosis at this time of follow-up. After 3 months after EOT (at timing of SVR), PCR of HCV RNA, AFP, (serum bilirubin, serum albumin, INR & serum creatinine) for calculation of CTP & MELD scores and abdominal US were done. While at 6 months after achieving SVR, (serum bilirubin, serum albumin, INR & serum creatinine) for calculation of CTP, MELD scores, AFP & abdominal US were done to reach the primary study outcomes. The primary outcomes of our study were the proportion of patients who achieved a reduction of CTP B to CTP A compensated cirrhosis after DAAs until the end of follow-up and the studying of the baseline characteristics associated with improvement from CTP B to CTP A compensated cirrhosis through calculation of baseline BE3A score. The secondary outcome was the proportion of patients who achieved SVR after 12 weeks after EOT. Events such as HE, worsening of ascites, worsening of CTP score, development of HCC or death were considered as study end points during DAAs while development of HCC, HCV relapse or death were considered as study end points during follow-up after EOT. Data was collected and statistically analyzed using SPSS and the following results were obtained: Regarding the demographic and clinical characteristics of our patients, we had 53.52% females and 46.48 % males with mean age 56.07 ±7.04. The BMI mean was 29.35 ± 4.27 with 50.70% were overweight, 38.03% were obese and 11.27% had normal weight. There were 9.39% hypertensive patients, 18.31% diabetic, 16.90% diabetic & hypertensive and 3.76% had thyroid disorders. The most common clinical decompensated characteristics were lower limb edema detected in 53.99%, mild ascites detected in 27.23%, jaundice detected in 5.16% , history of HE (grade 1-2) detected in 1.88%, varices detected in 92.43%, PHG detected in 73.51%, GAVE detected in 6.49 %, and splenomegaly detected in 98.12 %. According to liver ultrasound of the studied patients, we had 85.92% cirrhotic liver with normal size, 12.21% cirrhotic with enlarged size and 1.88% cirrhotic with shrunken size. Regarding DAAs regimens used in the study, SOF + DAC for 24 weeks were received by 52.11%, SOF + DAC + RBV for 12 weeks were received by 34.74%, SOF/ LDV for 24 weeks was received by 8.45%, SOF/ VEL for 24 weeks was received by 2.35%, SOF/ LDV + RBV for 12 weeks were received by 2.35%. Regarding the significant parameters during DAAs: There was a highly significant decrease in ALT& AST and a significant increase in platelet count during DAAs until EOT. There was a highly significant increase in serum bilirubin mainly indirect bilirubin and a significant decrease in Hb during DAAs plus RBV until EOT. Regarding the significant parameters at 3 months after EOT (SVR): there was a highly significant decrease in AFP, serum bilirubin, INR, MELD and CTP scores. There was a highly significant increase in patients with MELD <15 and decrease in patients with MELD >15. There was a highly significant improvement in CTP class due to there was a significant decrease in number of CTP B patients as compared to baseline (141 patients (66.20%) versus 213 patients (100%) respectively, attained CTP A in 71 patients (33.33%) and deteriorated to CTP C in one patient (0.47%). Regarding significant parameters at 36 weeks after start of treatment: there was a highly significant improvement in CTP class due to 103 patients (48.36 %) attained CTP class A. There was a significant difference between improved patients (attained CTP A) and non-improved patients regarding BMI, ALT, INR, ascites and BE3Ascore but at multivariate analysis, the BE3A score was the only significant baseline predictor for improvement from CTP B to CTP A (1.009 – 4.23 OR, 95% CI for OR, p = 0.05). Regarding the significant parameters at 6 months after SVR (end of the study): there was a significant decrease in number of ascitic patients, AFP, bilirubin, INR, MELD and CTP scores. There was a significant increase in serum albumin. There was a significant increase in number of patients with MELD <15 and decrease in number of patients with MELD >15. So, our study declared that, HCV DAAs in CTP B cirrhotic patients led to an improvement in mean CTP score and CTP class on follow-up at SVR, 36 weeks of treatment start and 6 months after SVR. Regarding primary study outcome, there was 55.87% met the primary end point of attaining CTP A at 6 months after SVR. There was a significant difference between improved patients (attained CTP A) and non-improved patients regarding ALT, ascites, albumin, INR, CTP score and BE3A scores but at multivariate analysis, ALT was the only significant baseline predictor for improving from CTP B to CTP A (1.040 – 5.889 OR, 95% CI for OR, p = 0.040). Regarding secondary study outcome, SVR 12 was achieved in 97.33% and virologic relapse in 2.74%. HCV DAAs were safe in CTP B patients with mild tolerable side effects. We had 33 patients who showed drug related tolerable side effects, of them 13 patients had anemia, 9 patients had fatigue, 7 patients had headache and 4 patients had diarrhea. Also, we had 33 DROP out patients during the study including 2 deaths. In summary, it was shown that a high baseline ALT (> 60 IU/L) was the predictor of improvement of CTP B to CTP A at 6 month after SVR. A high baseline BE3A score was associated with improvement of CTP B to CTP A at 36 weeks of treatment start. Treatment with HCV DAAs was effective and safe with improving clinical and biochemical abnormalities in CTP-B cirrhosis.