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Hepatitis G virus infection before and after liver transplantation. Liver Transplantation Database.

The hepatitis G virus is a newly discovered flavivirus that has been linked to acute and chronic hepatitis of unknown cause. We determined the prevalence of hepatitis G virus infection in 179 selected patients undergoing liver transplantation at three centers participating in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Pretransplantation and posttransplantation specimens were tested for hepatitis G virus RNA by polymerase chain reaction. Before transplantation, 9 of 38 (24%) patients with fulminant hepatic failure, 9 of 62 (15%) with cryptogenic cirrhosis, 3 of 35 (9%) with cholestatic liver disease, and 5 of 44 (11%) with chronic hepatitis C were positive for hepatitis G virus RNA (P = .27). Patients with and without viral RNA were similar in clinical features, liver test abnormalities, and survival after transplantation. Posttransplantation serum specimens were tested from 73 patients; 9 of 11 (82%) who were positive for viral RNA before transplantation remained positive, but 35 of 62 (56%) patients who were initially negative became positive after transplantation, a rate consistent with that predicted from the number of blood products administered. Only 5% of de novo HGV infections could be attributed to preexisting hepatitis G virus RNA in the donor. Comparison of patients with and without hepatitis G virus infection showed no difference in incidence of hepatitis after transplantation. Thus, hepatitis G virus infection was present in 15% of patients before and appeared de novo in half of patients after liver transplantation. Although hepatitis G virus infection was not associated with poor outcome, the frequency of this infection after transplantation calls for further long-term evaluation.

Adult↗

[Pathologic diagnosis of 1123 post-transplant liver biopsies from 665 liver transplant patients].

OBJECTIVE: To summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx). METHODS: 1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples. RESULTS: In the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0). CONCLUSIONS: This study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.

Adolescent↗

Hepatic transplants. Liver transplantation: an OR nurse's perspective.

1. Advanced surgical technique, improved immunosuppressive drug therapy, and an increased public awareness of the need for donor organs has resulted in liver transplantation being recognized as an available option for the treatment of end-stage liver disease. 2. The evaluation process is extensive. Medical and surgical assessments are done through a complete history and physical examination; diagnostic testing ranges from blood typing and serologies to radiologic and consultant procedures; and psychological and psychosocial evaluations are done for the patient and family. 3. Ongoing research in organ preservation, immunosuppressive drug therapy, and surgical technique has helped to make liver transplantation programs successful.

Anastomosis, Surgical↗

HCV infection of the transplanted liver: changing CD81 and HVR1 variants immediately after liver transplantation.

The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients. Clones of RT-PCR product were directly sequenced to identify HVR1 quasispecies variants. Explanted liver and serial allograft biopsies in recipients with HCV were examined by immunohistochemistry (IHC) for CD81 expression. Examination of HVR1 sequences demonstrated that only a fraction of the quasispecies variants recovered from each patient's blood sampled immediately prior to transplantation associated with and infected the allografts. Genetic diversity at HVR1 decreased with reperfusion but did not significantly decrease with infection. Expression of CD81 varied during the immediate post-transplant period. In conclusion, HVR1 quasispecies variants differentially associate with, and infect allografts, after liver transplantation. Additionally, allografts express variable amounts of CD81 after transplantation.

Amino Acid Sequence↗

Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model.

Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

Adenoviridae↗

Reduced size liver transplantation, split liver transplantation, and living related liver transplantation in relation to the donor organ shortage.

Because of the shortage of cadaveric donors, three techniques of partial liver grafting have been developed. These techniques are placed in perspective in relation to the organ shortage. Reduced size liver transplantation (RSLTx) is widely used and has results comparable to those from whole liver grafting. However, this technique, while benefitting pediatric patients, reduces the adult donor liver pool. It also makes inefficient use of an available adult donor liver. In split liver transplantation (SPLTx), the whole liver is used after bipartition for two recipients. The results are comparable to those of RSLTx. The problem with SPLTx is that it is a very demanding technique applied only in centers with extensive experience with liver resection and reduction. Living related liver transplantation (LRLTx) yields excellent results; however, it places an otherwise healthy person at risk. It is argued that instead of performing risky operations on healthy persons, the health authorities should take specific measures to alleviate the organ shortage. In the meantime, SPLTx should be developed further because of its optimal use of donor tissue. As for LRLTx, its excellent results and the present shortage of size-matched pediatric liver donors justify its use, at least for now.

Adult↗

[Cost-effectiveness analysis of long-term liver transplantation; the liver transplantation program of Groningen 1979-1991].

A medical technology assessment of the liver transplantation programme of Groningen University Hospital, which was commissioned by the Dutch National Health Insurance Board, is discussed. The results of all 152 liver transplantations performed between 1979 and November 1990 were analysed. The main objective of the study was to evaluate the long-term effects of liver transplantation. Five years after transplantation 59% of the adult patients were still alive. The survival probability depended greatly on the primary liver disease. Mortality and morbidity occurred mainly within the first year after transplantation. Thereafter the prospects for the patients were excellent, with regard to both the probability of survival and the quality of life. The costs of liver transplantation could be calculated only for patients with primary biliary cirrhosis and other forms of biliary cirrhosis, not caused by hepatitis B infection or alcohol abuse. For these patients the costs of a liver transplantation were estimated at HFl. 263,000--(with a 10% margin), 10 years of follow-up included and corrected for the costs that would have been made for the treatment of the liver disease. For this population of patients a liver transplantation costs between Hfl. 64,000--and Hfl. 79,000--per life year gained, 10 years of follow-up included. Costs of cyclosporin still take up a major part of the costs. The need for liver transplantation in the Netherlands was estimated at between 35 and 126 transplantations per year, depending on indications, contraindications, referral policy and the percentage of retransplantations.

Adolescent↗

Splenic artery aneurysms in liver transplant patients. Liver Transplant Group.

BACKGROUND/AIMS: The purpose of the study was to investigate the incidence of and risk factors for splenic artery aneurysms in liver transplant patients. METHODS: Medical records and the pre- and 1-year postoperative angiograms of 337 liver transplant patients were reviewed to assess the presence and characteristics of these aneurysms. RESULTS: Forty-five patients with aneurysms were identified (13%): 41 cases in 242 adult patients (17%) and four (4%) in 95 children (p<0.01). The female-to-male ratio was 2:1. The majority of the aneurysms (87%) were located in the distal third of the splenic artery and the majority (87%) of the patients presented multiple aneurysms. In patients without portal hypertension no aneurysms were identified, whereas in 16% of the patients with portal hypertension aneurysms were found (p<0.001). In adult patients the incidence of splenic artery aneurysms was significantly higher in patients with parenchymal diseases than in patients with cholestatic diseases (p<0.0001). Two patients (4%) died due to rupture of the aneurysms. Control angiographies, 1 year after liver transplantation, showed no changes in size and number of the aneurysms, and no new aneurysms were identified. CONCLUSIONS: The incidence of splenic artery aneurysms in liver transplant patients is 13%. They are generally multiple and located in the distal third of the splenic artery. The incidence is higher in women and in patients with parenchymal liver disease and portal hypertension. The incidence of rupture was 4%.

Adolescent↗

Normalised intrinsic mortality risk in liver transplantation: European Liver Transplant Registry study.

BACKGROUND: No model exists for liver transplantation to estimate the mortality risk in a given patient, and no standard by which to assess performance in different centres. We investigated the intrinsic mortality risk in the absence of known mortality risk factors. METHODS: We identified mortality risk factors and risk ratios quantified in data from the European Liver Transplant Registry (22,089 patients at 102 centres in 18 countries) registered from 1988 to 1997. To develop a model of the intrinsic risk and the risk ratios for specific factors, univariate and multivariate analyses were done separately for the overall population, for adults, and for children younger than 15 years, and the number of deaths were estimated. We validated the model by comparing mortality in patients without risk factors with the model-adjusted mortality in patients with risk factors. FINDINGS: Overall 5-year and 8-year actuarial survival was 66% (95% CI 65-66) and 61% (60-62). 65% of deaths occurred within 6 months. Retransplantation, transplantation for cancer, acute liver failure, fewer than 20 split-liver grafts per year, and a centre workload of fewer than 25 transplants per year were the main risk factors of 12 identified factors. 1-year and 5-year death rates among adults with no risk factors were similar to model estimates (15 [13-16] vs 14% [13-15], and 22 (20-24) vs 23% [21-24]). Corresponding data for paediatric transplants were 9% (7-12) compared with 11% (9-12) and 13% (10-17) compared with 14% (11-16). The reduction of mortality risk in high-volume centres was even greater in patients without risk factors (48 vs 23%, p<0.001). INTERPRETATION: The normalised intrinsic mortality risk can be combined with the relative risk ratios of known risk factors to better estimate the mortality risk of a given procedure in a given patient. Centres can assess performance by removing potential bias of donor and recipient selection.

Adolescent↗

[Experiences with liver transplantation and liver transplantation combined with Whipple's operation in Klatskin tumor].

In a retrospective Study on patients with type III/IV Klatskin tumors, results of liver transplantation and liver replacement in combination with a Whipple procedure and extensive lymph node dissection (six and four patients, respectively) were compared. The combined ultraradical approach was not associated with higher peri- and postoperative morbidity and mortality, and seems to offer a chance for better results in terms of tumor-free survival.

Adult↗

Surgical techniques of orthotopic rat liver transplantation.

Liver transplantation in rats is frequently used as a transplantation model. Although liver transplantation in larger laboratory animals such as dogs and pigs is technically easier, the rat has become the most important subject for experimental liver transplantation because of the availability of genetically defined animals. Numerous surgical techniques have been developed that permit the investigator to carry out studies with high clinical relevance. In this article the principal models of orthotopic rat liver transplantation and their technical modifications of vessel anastomoses, rearterialization, and bile duct reconstruction techniques are reviewed. More than 20 transplantation models are described in detail and demonstrated with clear illustrations. Finally, the advantages and uses of all the surgical procedures (e.g., suture and cuff anastomoses, bile duct anastomoses, and rearterialization techniques), specific problems, and survival criteria are discussed and the experiences of investigators who applied these techniques are analyzed. In conclusion, an overview and critical evaluation of all surgical techniques of orthotopic rat liver transplantation are given, together with instructions for learning these techniques.

Animals↗

Review: hepatitis B and liver transplantation.

Liver transplantation in hepatitis B virus (HBV)-infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in non-immuno-compromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV-DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti-HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that and potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine (2',3',dideoxy,3',thiacytidine) and famciclovir (a guanosine analogue). Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post-transplant HBV recurrence.

Hepatitis B↗

[Splitting liver transplantation. Orthotopic liver transplantation in two recipients with a single donor liver].

Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. Since either lobe can be used in preparing a reduced-size graft, both lobes can become grafts, if acceptable vascular pedicles and bile ducts can be established for each one. We report and demonstrate a technique, in which a donor liver has been split and was used to transplant in two recipients.

Anastomosis, Surgical↗

Spectrum of CT findings in pediatric patients after partial liver transplantation.

Liver transplantation is an accepted therapy for patients with severe liver diseases. In pediatric liver transplantation, the application of reduced-size and split-liver transplantation has expanded the donor pool. The development of living related donor partial liver transplantation has further increased the availability of donors. Complications in patients after living related transplantation include hepatic arterial thrombosis, portal venous stenosis and thrombosis, hepatic venous stenosis, biliary stenosis or leak, biloma formation, fatty liver, extrahepatic fluid collection, posttransplantation lymphoproliferative disorder, and organ rejection. Ultrasonography is the primary imaging modality for evaluation of the vascular system of patients after liver transplantation, and computed tomography is useful to help diagnose hepatic parenchymal abnormalities including infarction, congestion, and fatty change; intrahepatic biliary damage; and extrahepatic disorders, including abnormal fluid collections, varicose veins, and lymphadenopathy.

Child↗

Medical problems occurring after orthotopic liver transplantation.

Liver transplantation is complicated by specific medical problems. Diabetes mellitus occurs in 4-20% of patients undergoing liver transplantation. Patients with primary sclerosing cholangitis and ulcerative colitis experience up to a 13% incidence of colon cancer after transplantation. Lymphomas occur in 1-3% of patients after transplantation and account for 57% of malignancies occurring in adult patients. Atraumatic bone fractures occur in 22-38% of patients and neurological complications, including seizures, headache, and neuropathy occur in 19-47% of patients following liver transplantation. Patients undergoing liver transplantation may experience recurrence of their primary liver disease: hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, or primary sclerosing cholangitis. In patients not receiving immunoprophylaxis after transplantation for chronic hepatitis B, recurrent hepatitis B is seen in up to 90% of patients. This can be markedly reduced with hyperimmune globulin immunoprophylaxis. Recurrent hepatitis C is seen in the majority of patients; current treatment modalities are inadequate. Recurrence of primary biliary cirrhosis or primary sclerosing cholangitis in the allograft is infrequent. Autoimmune hepatitis may recur in up to 26% of patients following liver transplantation. Primary disease recurrence in the allograft and preventive strategies are discussed.

Bone Diseases↗