小儿肝移植后进行性肝组织损伤

The long-term histological outcome after pediatric liver transplantation (OLT) is not yet fully understood. De novo autoimmune hepatitis, consisting of histological chronic hepatitis associated with autoantibody formation and allograft dysfunction, is increasingly recognized as an important complication of liver transplantation, particularly in the pediatric population. In this study, 158 asymptomatic children with 5-year graft survival underwent protocol liver biopsies(113, 135, and 64 at 1, 5, and 10 years after OLT, respectively). Histological changes were correlated with clinical, biochemical, and serological findings. All patients received cyclosporine A as primary immunosuppression with withdrawal of corticosteroids at 3 months post OLT. Normal or near-normal histology was reported in 77 of 113 (68%), 61 of 135 (45%), and 20 of 64 (31%) at 1, 5, and 10 years, respectively. The commonest histological abnormality was chronic hepatitis (CH), the incidence of which increased with time[25/113 (22%), 58/135 (43%), and 41/64 (64%) at 1, 5, and 10 years, respectively) (P< .0001)]. The incidence of fibrosis associated with CH increased with time [13/25 (52%), 47/58 (81%), and 37/41 (91%) at 1, 5, and 10 years, respectively)(P < .0001)]. The severity of fibr- osis associated with CH also increased with time, such that by 10 years 15%had progressed to cirrhosis. Aspartate aminotransferase(AST) levels were slightly elevated in children with CH (median levels 52 IU/L, 63 IU/L, and 48 IU/L at 1, 5, and 10 years, respectively), but this did not reach statistical significance compared with those with normal histology. On multivariate analysis, the only factor predictive of chronic hepatitis was autoantibody positivity (present in 13%and 10%of children with normal biopsies at 5 and 10 years, respectively, and 72%and 80%of those with CH at 5 and 10 years, respectively)(P < .0001). Four children with CH and autoantibodies, who also had raised immunoglobulin G (IgG) levels and AST greater than 1.5x normal fulfilled the diagnostic criteria for de novo autoimmune hepatitis(AIH). Another two were found to be hepatitis C positive. No definite cause for CH could be identified in the other cases. In conclusion, chronic hepatitis is a common finding in children after liver transplantation and is associated with a high risk of developing progressive fibrosis, leading to cirrhosis. Standard liver biochemical tests cannot be relied on either in the diagnosis or in the monitoring of progress of chronic allograft hepatitis. In contrast, the presence of autoantibodies is strongly associated with the presence of CH. The cause of chronic hepatitis in transplanted allografts is uncertain butmay be immunemediated, representing a hepatitic form of chronic rejection.

对乙酰氨基酚引起的肝中毒

Aim:To identify the clinical and biochemical risk factors associated with outcome of paracetamol induced significant hepatotoxicity in children. Methods:Retrospective case notes review of those with paracetamol overdose admitted from 1992 to 2002. Patients were analysed in two groups:group I recovered after conservative treatment and group II developed progressive liver dysfunction and were listed for liver transplantation. Results:Of 51 patients (6 males,45 females,aged 0.8-16.1 years),6 (aged < 7 years) received cumulative multiple doses,and 45 a single large overdose (median 345 mg/kg,range 91-645). The median (range) interval to hospital at presentation post-ingestion was 24 hours (4-65) and 44 hours (24-96) respectively in groups I and II. Patients received standard supportive treatment including N-acetylcysteine. All children in group I survived. In group II,6/11 underwent orthotopic liver transplantation (OLT) and 2/6 survived; 5/11 died awaiting OLT. Cerebral oedema was the main cause of death. Children who presented late to hospital for treatment and those with progressive hepatotoxicity with prothrombin time >100 seconds,hypoglycaemia,serum creatinine > 200 μmol/l,acidosis (pH<7.3),and who developed encephalopathy grade III,had a poor prognosis or died. Although hepatic transaminase levels were markedly raised in both groups,there was no correlation with necessity for liver transplantation or death. Conclusion:Accidental or incidental paracetamol overdose in children may be associated with toxic liver damage leading to fulminant liver failure. Delayed presentation and/or delay in treatment,and hepatic encephalopathy ≥grade III were significant risk factors,implying poor prognosis and need for OLT. Prompt identification of high risk patients,referral to a specialised unit for management,and consideration for liver transplantation is essential.