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العنوان
Interleukin-28b polymorphism and its relation to biochemical and viral changes in chronic hcv after liver transplantation /
المؤلف
Sayed, Mohammed Mohammed.
هيئة الاعداد
باحث / محمد محمد سيد
مشرف / أمانى حلمى لاشين
مناقش / انتصار حسين الشرقاوى
مناقش / عصام أنور مرسى
مناقش / حاتم سمير عبد الرءوف
الموضوع
Liver transplantation. Transplantation, Homologous. Viruses.
تاريخ النشر
2014.
عدد الصفحات
198 p. :
الفهرس
Only 14 pages are availabe for public view

from 198

from 198

Abstract

Hepatitis C related ESLD is the main indication for liver transplantation and represents almost 89.8% of LT in Egypt. The influence of HCV infection on allograft histology is highly variable with several factors, it has been suggested that these factors may accelerate HCV reinfection of the allograft.
IL-28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.
The aim of this study was to evaluate the relationship between the interleukin-28B polymorphism (rs12979860) and biochemical and viral changes in chronic HCV after living donor liver transplantation.
This study was carried out on 50 patients with chronic HCV-related liver disease who underwent living donor liver transplantation in El Sahel Teaching Hospital, 40 patients were males and 10 patients were females. Their ages ranged from 17 to 60 years with mean age 47.9±9.4.
 All the studied patients were subjected to the following:
Pre-transplantation Data:
I. Detailed history and Clinical examination:
II. Laboratory and Radiological investigations:
• Complete blood count (CBC).
• Liver tests.
• HCV RNA PCR (Quantitative).
• Serum creatinine, blood urea, serum Na and serum K.
• Anti-nuclear antibody (ANA).
• Alfa feto protein (AFP).
Imaging data was mainly ultrasound and Doppler findings as cirrhosis, ascites, splenomegaly, presence of focal lesions, portal vein thrombosis and the kidney condition.
Using the previous data, Child-Trucott-Pugh classification and MELD (model of end stage liver disease) score were done.
Post-transplantation follow up:
I. Detailed history.
II. Full clinical examination.
III. Laboratory part of the work were collected, at the period from the 4th to the 6th month post-transplantation, from the recipient’s follow up reports and includes:
• CBC.
• Liver tests.
• Serum creatinine, blood urea, serum Na and serum K.
• AFP.
• HCV RNA PCR (Quantitative) at the 6th month post-transplantation.
IV. Liver biopsy indicated by unexplained elevated transaminases.
V. Specific genetic test:
Recipient’s IL-28B single nucleotide polymorphisms (rs12979860).
The results obtained can be summarized as follows:
The MELD score of the patients before transplant ranged between 8 and 27 with a mean of 16.4. BMI of patients ranged from 20 to 31 with mean of 27.2. 94% of the studied patients were Child C, 4% were Child A and 2% were Child B.
Pre-transplant 88% of the studied patients had ascites, 66% had jaundice, 54% had loss of weight, 42% had history of hepatic encephalopathy, 22% had variceal bleeding and 32% of patients was proved to have HCC.
The donor age ranged from 21 to 40 years with mean of 27.9. Donor liver steatosis ranged from 0% to 15% with mean of 4.2%.
IL-28B rs12979860 SNP genotypes were assessed and showed that 20% of recipients were of the CC genotype, 62% were CT genotype and 18% were TT genotype. 50% of the studied group had +ve CMV PCR post-transplant.
Post-transplant complications were assessed and showed that 34% of the recipients had at least one episode of acute rejection, 32% had HCV recurrence proved by liver biopsy indicated by un-explained elevated transaminases, 22% developed biliary complications, 2% have recurrent HCC and 2% suffered from attack of bleeding peptic ulcer.
At the time of our assessment, 42% of the recipients were using Tacrolimus (FK)+ Mycophenolate Mofetil (MMF) as immunosuppressive, 26% were using Tacrolimus alone, 20% were using Cyclosporine+MMF, 8% were using Cyclosporine alone, 2% were using Everolimus+MMF and 2% were using Everolimus alone.
The authors assessed relationship between IL-28B SNP genotypes and pre and post-transplant biochemical, virological and clinical outcomes:
The relationship between IL-28B SNP and pre-transplant laboratory parameters was highly significant with INR and Alkaline phosphatase, significant with MELD score and non significant in relation to other parameters.
There was no significant correlation with either pre or post-transplant HCV viral load (HCV RNA PCR).
In the post transplant setting, there was significant correlation with only Hb level and white blood cell count and non significant with other parameters.
Il-28B SNP had no significant correlation with acute rejection, biliary complications, detection of CMV PCR or liver biopsy findings.
IL-28B SNP genotyping showed that C allele is the favorable allele and showed a highly significant correlation with pre-transplant presence of HCC and a significant correlation with post-transplant HCV recurrence.
As regard assessment of clinical HCV recurrence in relation to different risk factors:
Donor’s age was significant factor while liver steatosis was non significant factor affecting the clinical HCV recurrence.
Recipient’s age, gender and BMI were non significant factors affecting the post- transplant clinical HCV recurrence.
Pre-transplant platelet count and ascites were significant factors affecting clinical HCV recurrence while other pre-transplant clinical and laboratory variables were non significant.
Hepatitis C viral load pre-transplant and post-transplant were highly significant factors affecting clinical HCV recurrence.
Post-transplant mean ALT and AST were highly significant factors affecting the post-transplant clinical HCV recurrence.
Post-transplant mean serum albumin and mean Hb concentration were significant factors affecting the post-transplant clinical HCV recurrence while other post-transplant laboratory parameters were non significant.
The usage of mycophenolate mofetil (MMF) as immunosuppressive was a significant factor affecting the post-transplant clinical HCV recurrence.
Exposure to acute rejection and presence of CMV PCR were non significant factors affecting the post-transplant clinical HCV recurrence.