自身免疫性肝炎与肝移植

AIH是一类以自身免疫反应为基础,以高丙种球蛋白血症、高血清自身抗体为特征的肝脏炎症性病变,汇管区大量浆细胞浸润并向周围肝实质侵入形成界板炎症是其典型病理组织学特征。此病多见于女性(男女比例为1.0:3.6),任何年龄均可发病。免疫抑制剂是治疗AIH的常用药物,但部分患者仍然会发展至终末期肝硬化,或出现暴发性肝衰竭。此时,肝移植术成为治疗终末期AIH患者的有效方法,约占肝移植总数的5%。AIH肝移植患者的5年存活率和移植     

Viral hepatitis after liver transplantation

Recurrence of the original liver disease following liver transplantation is a typical complication in viral hepatitis. Recent advances, particularly the development of strategies to prevent or effectively treat hepatitis B, have led to substantial improvements in the post-transplantation outcome of hepatitis B candidates. While the efficacy of antivirals to treatrecurrent hepatitis C has improved in recent years, there is as yet no therapy to universally prevent recurrent infection, and tolerability of antivirals remains a matter of concern.     

De novo autoimmune hepatitis after liver transplantation

Allograft dysfunction with clinical, serologic, and histologic features resembling autoimmune hepatitis (AIH) may develop in pediatric and adult patients who have received a liver transplant (LT) for end-stage diseases other than AIH. This condition is now known as de novo AIH, although its pathophysiology is still uncertain and whether it represents a specific type of rejection or a genuine form of AIH is under debate. The occurrence of de novo AIH seems to be unrelated to the etiology of the disease necessitating liver transplantation, but it has been correlated with antiviral treatment in cases of hepatitis C virus (HCV) infection recurring after LT. Several investigators have reported adverse outcome of de novo AIH, including graft failure, particularly in cases with late diagnosis. Prompt treatment with prednisone, with or without azathioprine (in addition to the basic immunosuppressive regimen), seems to be the best option. The histology of de novo AIH is characterized by an infiltrate rich in plasma cells with significant interface hepatitis and perivenular necro-inflammatory activity. These features are not specific for autoimmune damage; therefore, other causes of graft dysfunction must be excluded. The final diagnosis may be a challenge in patients with recurrent hepatitis C, and requires careful clinical and pathologic assessment.     

Treatment of hepatitis C after liver transplantation

This article summarizes the current therapies, with particular emphasis on antiviral therapy. Because these alternatives have substantial limitations, pretransplant or early post-transplant recognition of patients with high risk of severe post-transplantation outcome is desirable to target these patients for intervention. Alternatively, the implementation of measures aimed at reducing or avoiding factors known to be associated with an aggressive recurrence is an additional strategy that needs to be explored.     

Autoimmune hemolytic anemia during treatment with cyclosporin after liver transplantation

Hemolytic anemia was observed in a 36 year-old liver transplant patient. The immunosuppressive regimen included cyclosporine A and prednisolone. Hemolysis appeared a few days after amoxicillin treatment. The presence of anti-D allo-antibodies, auto-antibodies active against erythrocytes, and an immuno-allergic phenomenon against erythrocytic membrane coated by cyclosporine was demonstrated. Increase of daily dose of prednisolone without modification of cyclosporine doses was followed by the disappearance of allo- and auto-sensitization. The role of amoxicillin in promoting these hemolytic phenomenons may be suggested.     

Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation

Although the development of de novo autoimmune liver disease after liver transplantation(LT)has been described in both children and adults,autoimmune hepatitis(AIH)-primary biliary cirrhosis(PBC)overlap syndrome has rarely been seen in liver transplant recipients.Here,we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis.His liver function tests became markedly abnormal 8 years after LT.Standard autoimmune serological tests were positive for anti-nuclear and antimitochondrial antibodies,and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus.Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis,which confirmed the diagnosis of AIH-PBC overlap syndrome.We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome;a novel type of autoimmune overlap syndrome.     

丙型肝炎相关肝病肝移植后丙型肝炎复发的防治

肝移植是慢性丙型肝炎相关终末期肝病惟一的有效治疗方法，但所有患者均可能出现移植后丙型肝炎复发，移植后5年内约25％～33％的患者可因丙型肝炎复发出现肝硬化，因此对其预防和治疗尤为重要，本文就丙型肝炎相关肝病肝移植后丙型肝炎复发的防治作一介绍。     

Herpes simplex virus hepatitis after pediatric liver transplantation

T. Hori, Y. Ogura, S. Okamoto, A. Nakajima, K. Kami, J. Iwasaki, Y. Yonekawa, K. Ogawa, F. Oike, Y. Takada, H. Egawa, J.H. Nguyen, S. Uemoto. Herpes simplex virus hepatitis after pediatric liver transplantation
Transpl Infect Dis 2010: 12: 353–357. All rights reserved Abstract: Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought‐provoking case of HSV hepatitis in a high‐risk recipient after living‐related liver transplantation (LRLT). A 1‐month‐old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody‐mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real‐time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.     

Pathogenesis of recurrent hepatitis C after liver transplantation

End-stage liver disease associated with hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. Recurrent HCV infection is nearly universal and disease progression is accelerated in the immunocompromised host. In the post-transplant setting, the HCV-specific immune response plays a critical role in viral surveillance and disease progression. A failure to mount an efficient response to HCV antigens, either because of selective defects in the host immune system or because of viral interference with the normal function of the immune cells, could account for the inability of most transplant recipients to eradicate HCV.     

Management of recurrent hepatitis C after liver transplantation

Hepatitis C virus (HCV) reinfection is almost universal in patients transplanted for HCV-related cirrhosis. The medium-term survival after orthotopic liver transplantation (OLT) is similar to other transplanted patients, but the long-term survival remains uncertain. The prevention and an effective treatment of progressive liver disease are the primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in combination, have been tried to treat or prevent HCV recurrence. Preliminary studies suggest a better chance of initial HCV clearance and better results in preventing HCV recurrence with combination therapy. IFN or ribavirin, as monotherapy, may normalize liver enzymes, but only gives rise to a transient virological response, without histological improvement. Combination IFN and ribavirin may be able to prevent progression of HCV-related graft disease, but indications and duration of treatment need further evaluation.
No clear association between type and dose of immunosuppressive and outcome of post-transplant HCV recurrence has been found. Strategies to minimize the effects of immunosuppressive drugs include dose reduction of all agents and the selective discontinuation of individual agents. Initial immunosuppression with a single drug may inhibit or delay the severe fibrosis, and further investigation with a single immunosuppressive regimen to evaluate the outcome of recurrent hepatitis C should be performed. The recent evidence that mycophenolate may have an antiviral effect needs a clinical confirmation.
Retransplantation survival is better with early retransplantation, and for indications not directly related to viral recurrence.     

Treatment of recurrent hepatitis C after liver transplantation

Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15% to 50% of the liver transplants performed in United States transplant programs. To maximize the long-term survival of liver transplant recipients who have HCV infection, eradication of infection is the ultimate goal. Pretransplant antiviral therapy with the goal of achieving viral eradication before transplantation is a consideration in some patients, especially those who have mildly decompensated liver disease. This article focuses on the management of liver transplant recipients who have HCV infection at the time of transplantation. Prophylactic and preemptive therapies, as well as treatment of established recurrent disease, are the strategies reviewed.     

Treatment strategy for hepatitis C after liver transplantation

A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over periods of two to three decades and require liver transplantation, although re-infection is common and leads to further adverse events, given that such patients receive life-long immunosuppression. Because of the critical organ shortage worldwide, living-donor liver transplantation has an important role in many countries, especially in the Far East. Despite previous arguments, the results of recent well-designed studies suggest equivalent outcomes for deceased-donor and living-donor liver transplantation. No specific immunosuppression regimen has proven advantageous, but the general rule is “low and slow”. Combined pegylated interferon and ribavirin therapy is the current standard treatment, but compared to this therapy in the immunocompetent population, its efficacy in clearing the virus remains low. Moreover, its general application is hindered by the high prevalence of intolerability, lowering its efficacy from the aspect of intention to treat. Retransplantation becomes an option when treatment for disease progression fails, but it should be considered at an earlier stage in patients with a lower MELD (model for end-stage liver disease) score compared to that used for primary transplantation, which is a great challenge with the current critical organ shortage. The need for new anti-HCV drugs to further delay disease progression or even to enhance viral clearance, presumably specific HCV life-cycle inhibitors, is urgent. The liver transplant community must maintain an open mind regarding the development of these drugs and focus on their availability for early clinical trials in liver transplant recipients.     

Management of recurrent hepatitis C infection after liver transplantation

Recurrence of hepatitis C virus remains a near-universal phenomenon after liver transplantation (LT) and is responsible for the high morbidity and low survival seen in these patients. The severity of recurrent disease varies depending on multiple factors, only some of which are modifiable. Antiviral therapy is associated with improved outcomes, but viral clearance is only attainable in a small percentage of this patient population. This patient population is in need of new therapeutic options, and it remains to be seen whether direct-acting antiviral agents will be the answer to this ongoing therapeutic question.