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| Author(s): |
Rodrigo Schuler Honorio
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2010-02-05 |
| Examining board members: |
Venancio Avancini Ferreira Alves;
Edson Abdala;
Maria Irma Seixas Duarte;
Evandro Sobroza de Mello;
Rosely Antunes Patzina
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| Advisor: | Venancio Avancini Ferreira Alves |
| Field of knowledge: | Health Sciences - Medicine |
| Indexed in: | Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP |
| Location: | Universidade de São Paulo. Biblioteca Central da Faculdade de Medicina; W4.DB8 SP.USP FM-2; H749av |
| Abstract | |
Background: Recurrent chronic hepatitis (RCH) is the rule after liver transplantation (LT) in hepatitis C virus (HCV) infected patients, with a faster fibrosis progression in allograft than in native liver. Many studies have pointed out that, even in the group of patients transplanted for HCV end-stage disease, there are distinct outcomes due to the influence of several clinical, demographic, laboratorial and histopathological factors. Objectives: Evaluate earlier changes that could be associated to severity of disease recurrence, with emphasis on histopathological findings at LT and follow up biopsies. Method: A retrospective cohort of forty one HCV infected patients who underwent LT between 1992 and 2004 was studied. Clinical data were recovered from hospital files and all liver tissue specimens were reviewed. The first liver biopsy after first month post-LT (FAF) and the first biopsy with chronic hepatitis (FCH) were considered to each patient. Expression of -smooth muscle actin in hepatic stellate cells by immunohistochemistry was also examined in these biopsies. Additionally, steatosis and chronic hepatitis parameters were quantified in all biopsies in each period after LT. Results: The mean age at LT was 51 yr; 72% were male; the median histological follow-up (time between LT and last liver biopsy) was 2234 days (785-4640) and the overall annual rate of fibrosis progression (RFP)was 0.62 (Ishak s score). Patients were classified in fast fibrosers (FF)when RFP>0.62,and when RFP<0.62.Time to histopathological diagnosis of RCH, early histopathological changes related to chronic hepatitis diagnosis and donor factors were not significantly different between both groups. Acute cellular rejection was more prevalent in SF (p=0.043), although FF presented significantly higher number of episodes than SF (p=0.036). It was observed an increase in BMI on FF and an decrease in BMI on SF between transplantation and the time of last liver biopsy (p=0.049). FF showed higher steatosis degree in native explanted liver (p=0.026) and showed a trend toward a lower steatosis degree between one month and one year post-LT (p=0.079). FF also presented higher lipofuscin deposition at FAF (p=0.024) and at FCH (p=0.048). FF and SF showed distinct patterns of lobular inflammatory infiltrate in FHC, with a predominantly lymphocytic type in FF and a mixed one in SF (p=0.043). A distinct pattern of iron deposition in FAF, predominantly in Kupffer cells in FF and in both Kupffer cell and hepatocyte in SF was also detected. Hepatic stellate cells were more prevalent in FF when examined in portal/septal area by immunohistochemical expression of -smooth muscle actin in FHC (p=0.057). All other histological findings did not reach statistical significance as predictors of faster disease progression. Conclusion: Some minor histopathological changes not usually associated to chronic hepatitis diagnosis might contribute to our understanding of the RCH pathogenesis and could be useful in identifying potentially worse outcome patients after LT. If factors related to lipid metabolism (liver steatosis and BMI variation) could protect against fibrosis progression or are direct consequences of the patient´s clinical status deserves further evaluation (AU) | |