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Because of the almost universal recurrence of hepatitis B surface antigenemia (HBsAg) after liver transplantation, some centers have questioned whether these patients are appropriate allograft candidates. Since January 1984, 51 patients with hepatitis B (HBV) underwent OLT at our center. No therapy was given to prevent reinfection. Three patients underwent retransplantation. The indications for transplant included fulminant HBV (13 patients), chronic HBV (33 patients), and hepatocellular carcinoma (HCCA) in addition to HBV (5 patients). Incidental HCCA was found in 2 of the 33 patients thought to have only chronic HBV. Actuarial survival for the entire group was 57% at 1 year and 54% at 3 years. Of the 23 patients who died, only 4 deaths were attributable to recurrent HBV liver disease. Four patients survived less than 4 days due to primary graft nonfunction. Ten patients died in the first 3 months from sepsis. Although all patients who died beyond 30 days had recurrent HBsAg, only 4 deaths were attributable to recurrent HBV. The remaining 5 deaths were caused by portal vein thrombosis, bile leak, lymphoma, pancreatitis, and sepsis occurring at 15 months. Excluding the 4 patients who died from primary graft nonfunction, actuarial survival was 63% at 1 year and 60% at 3 years. Of the 28 survivors, 24 are HBsAg positive; however, only 5 have recurrent HBV liver disease. Multiple factors were evaluated to determine their influence on survival; i.e., HBV serology, United Network for Organ Sharing status, fulminant versus chronic HBV, incidence of rejection, immunosuppression, transfusion requirements, and presence of HCCA. Of these, only the presence of HCCA adversely affected outcome. Of the 7 patients with HCCA and HBV, 6 patients died within the first 6 months and 1 patient has recurrent HBV liver disease at 25 months. Actuarial survival excluding those patients with HCCA was 64% at 1 year and 61% at 3 years. Based on our results, patients with HBV and associated HCCA have a poorer prognosis and should probably be excluded from transplantation. Although the survival for patients with HBV undergoing liver transplantation is inferior to that expected in patients with some other diagnoses, long-term survival can be achieved in a majority of these patients despite recurrence of HBsAg. We believe that appropriately selected patients with a diagnosis of HBV alone should continue to be candidates for liver allografts.
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PMID:Should liver transplantation be performed for patients with hepatitis B? 800 92

While orthotopic liver transplantation (OLT) has become the treatment of choice for most irreversible end-stage liver diseases, its role in patients with hepatitis B (HBV) infection is controversial. A high risk of reinfection of the transplanted graft, associated with significant morbidity and mortality, has been reported. Although passive and active immunization can delay reappearance of the virus in the allograft, there is not yet an effective therapy for recurrent HBV infection in liver transplant recipients. Between October 1985 and March 25, 1991, 28 OLT in 25 patients with acute and chronic HBV infections were performed. Twelve of the patients were HBV DNA-negative, six were HBV DNA-positive, and seven were not tested prior to transplantation. Only the 19 patients surviving more than 100 days after transplantation were considered to have sufficient duration of follow-up (mean 734 days; range 500-1545) to include in analysis of recurrence. Five (26%) were free of recurrent disease at the time of last follow-up (mean 1031 days, range 526 to 1770 days. Recurrent HBV in the allograft, as defined by positive immunoperoxidase stains of biopsy sections for viral antigens, was detected in 74% (13 male, 1 female; 7 Asian, 7 white) at a mean of 134 days posttransplantation. Histological changes of viral hepatitis, first appearing an average of 157 days (range 95-326) posttransplantation, were evident in 13 of 14 with positive immunostaining. Twelve of the 14 patients were treated, on an open trial basis, with intravenous and oral prostaglandin E (PGE) because of deteriorating clinical condition. Eleven of the twelve responded to PGE with an initial drop in serum transaminases, improvement in coagulopathy and resolution of encephalopathy. One patient failed to respond and died of a myocardial infarction within 9 days of institution of therapy. Three of the eleven patients with an initial response relapsed and died in liver failure as a direct result of recurrent HBV after 13, 16, and 37 days of treatment in association with generalized sepsis. Eight of the 12 patients (67%) had a sustained favorable response to PGE therapy (mean follow-up 737 days, range 403-1545). All patients with a sustained response had accompanying improvement in histology and reduction in viral antigen staining in hepatocytes. Treatment with PGE appeared to be of benefit in recurrent HBV infection of the transplanted liver with an initial response rate of 92% and a sustained response rate of 67%.
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PMID:Prostaglandin E in the treatment of recurrent hepatitis B infection after orthotopic liver transplantation. 804 36

The article deals with the results of work conducted according to the orthotopic liver transplantation (OLT) program from January 1990 to January 1992. To select the patients for OLT, 54 persons (24 males and 30 females aged from 12 to 55 years) with diffuse (34) and focal (20) diseases of the liver were examined. OLT was indicated for 19 patients who were registered in the waiting list. In the period of waiting for the donor organs, 5 persons died, 3 refused to undergo OLT, and 4 remain on the waiting list. Eight OLT (including one retransplantation) were conducted on 7 patients. The indications for OLT in these patients were: unresectable hepatocellular carcinoma (4), cirrhosis of the liver of viral etiology (1), fulgurant form of hepatitis B (1), transplant rejection crisis which could not be arrested (1). Immunosuppression was conducted by the two- and three-component programs with the use of corticosteroids, cyclosporine A, and azathioprine. Eight crises of transplant rejection were encountered, successful retransplantation of the liver was accomplished for one of two crises which could not be arrested. The survival of the operated on recipients ranged from 3 days to 15 months. Various complications (mainly hemorrhagic and infectious) were encountered in the posttransplantation period. At the time that the article is written, 3 patients are living for 15, 9, and 4 months (after retransplantation of the liver in the last case), their condition is satisfactory. The death of the other recipients was caused by candidosepsis (on the 40th day), polyorganic insufficiency (on the 10th and 3rd days), sepsis (on the 12th day). The results of the liver transplantation program correspond to those of transplantation centers in other countries in the period of OLT mastering.
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PMID:[Orthotopic liver transplantation (first clinical experience)]. 808 67

Liver transplantation of hepatitis B surface antigen (HBsAg)-positive patients has been associated with high morbidity and mortality secondary to hepatitis B (HB) recurrence in the graft. Eight patients of the Queensland Liver Transplant Service were HBsAg positive pretransplant. Six acquired HB infection of the graft, one developed serological recurrence of HB before early death from sepsis, and one HB e antigen-negative patient permanently cleared the virus. HB-infected grafts showed early expression of viral antigen, acute hepatitis, fibrosing cholestatic hepatitis, chronic active hepatitis, cirrhosis, or minimal changes associated with a carrier state. Only in the latter case was HB mild and nonprogressive. Cases of fibrosing cholestatic hepatitis progressed rapidly to liver failure; they showed fibrosis and plates of ductular epithelium extending from portal tracts into lobules, cholestasis, ballooning of hepatocytes, and prominent hepatocyte expression of viral antigens. Perioperative HB immunoglobulin proved ineffective in preventing HB recurrence. One other patient became HBsAg positive for the first time after retransplantation; he developed severe acute hepatitis, then chronic active hepatitis. Our biopsy findings support the view that, in liver allografts, the HB virus may be directly cytopathic.
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PMID:Hepatitis B virus infection in liver allografts. 831 8

Indications for liver transplant in acute fulminating hepatitis (AFH) are predominantly affected by the high mortality of this spontaneous evolution (80-100%). At present patients with AFH have priority for transplant since they form part of the 0 emergency group according to the National Transplant Organisation. During the period between 1986 and the end of February 1992, a total of 254 liver transplants were performed in 202 patients (52 retransplants). In 26 patients (12.8%) (16 females and 10 males) the indication was fulminating acute hepatitis. Etiology was unknown in 20 patients, secondary to hepatitis B in 4 and to hepatitis A in 1, and was caused by isonazide ingestion in 1 case. The age limits were 3-60 years (X = 31.5 years). An isogroup graft was performed in 16 patients (61.5%), compatible in 3 (11.6%) and incompatible in 7 (26.9%). Due to anthropometric differences, a partial graft was used in 7 patients (26.9%); in 2 of the latter the graft was taken from the same donor ("split-liver"). Placement was always orthotopic with resection of the retrohepatic vena cava in 25 patients and its preservation in 1 (left lobe of split-liver). Peroperative (30 days) mortality was 23% (6/26); 2 due to cerebral death, 2 due to sepsis, 1 due to multisystemic insufficiency (MSI) and 1 due to acute pancreatitis. Four patients (15.3%) died some time after transplant; 1 after 5 months due to broncho-pulmonary complications, 1 after 7 months due to subacute hepatitis, 1 after 3 months due to respiratory failure and the last after 5 months due to anoxic encephalopathy and lung infection. Ten patients (39.4%) were re-transplanted; 4 following chronic rejection, 4 due to primary graft no function, 1 due to arterial thrombosis and 1 due to recurrent hepatitis (with cirrhosis). Two of the latter patients died intraoperatively due to coagulopathy and hemorrhage, and 3 following surgery (1 due to sepsis, 1 due to respiratory complications and 1 due to respiratory insufficiency). Two patients underwent a second re-transplant (1 due to chronic rejection and 1 due to recurrent hepatitis) and of these 1 died peroperatively due to sepsis and MSF. Overall mortality was therefore 61.5% (16/26) and the actuarial survival rate of 17 patients (10 living + 7 postoperative deaths) was 68% at 12 months and 52.9% at 36 months. Even if peroperative mortality is relatively high, liver transplant is currently the elective treatment for fulminating acute hepatitis.
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PMID:[The treatment of acute liver failure due to fulminating hepatitis by total or partial orthotopic liver transplantation. The clinical results]. 832 33

The risk of acquiring diseases from transfusion of blood and blood products is well recognized and the issue of parvovirus in haemophiliacs is not a new one. We report two patients with haemophilia acquiring iatrogenic parvovirus B19 infection, resulting in life-threatening sepsis in one, and immunocompetent adult. Over the last 10 years there has been great progress in manufacturing safer products with regard to enveloped viruses such as HIV, hepatitis B and C. A recent outbreak across Europe of hepatitis A in haemophiliacs treated with plasma-derived factor VII concentrates has made haemophilic treaters concerned about the known (parvovirus B19 and hepatitis A) and the unknown non-lipid enveloped viruses that may be contained in the clotting factor concentrates, because these are resistant to the existing viral inactivating techniques. The possibility of HIV itself mutating into a non-lipid enveloped virus emphasizes the need to seek and use safer products.
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PMID:Transmission of symptomatic parvovirus B19 infection by clotting factor concentrate. 863 48

In a retrospective long-term follow-up study the clinical course of liver disease was examined in renal allograft recipients with hepatitis C virus (HCV) infection and negative hepatitis B surface antigen under immunosuppressive therapy. We compared 42 anti-HCV antibody (anti-HCV) positive patients (study group) to 213 anti-HCV negative patients (control group). All patients received immunosuppressive therapy. Measurements were made of the following: aminotransferases, bilirubin, albumin, gammaglobulins, ascites, spleen diameter, HCV RNA, and anti-HCV antibody. We found all but four anti-HCV positive patients to be HCV RNA positive prior to transplantation. There were no differences in overall mortality or mortality secondary to liver disease or sepsis. Normal liver enzymes were found in 13 (31%) anti-HCV positive and in 137 (64%) anti-HCV negative patients during the whole mean observation period of 65 months (range 10-215). Aminotransferase activity decreased in anti-HCV positive and negative patients during the observation period. Liver function with regard to synthesis and excretion was normal in anti-HCV negative and anti-HCV positive patients. No signs of portal hypertension were observed in the anti-HCV positive group. Neither the different immunosuppressive regimens nor the antirejection therapy led to differences between anti-HCV positive and negative groups with respect to liver function and did not alter the clinical course. We conclude that HCV infection in patients under immunosuppressive therapy causes only a mild liver disease, as determined by clinicochemical and clinical parameters, and that mortality rate is not increased.
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PMID:Immunosuppressive therapy and hepatitis C virus infection: the clinical course of liver disease. 884 53

A retrospective review of 130 patients with peripheral-type cholangiocarcinomas (PTCC), hilar-type cholangiocarcinomas (HTCC), extrahepatic cholangiocarcinomas (EHCC), gallbladder cancers (GBCA), and periampullary cancers (PACA), seen at National Cheng Kung University Hospital and Tainan Municipal Hospital from June 1987 to July 1993 was performed. There were 47 (36%) HTCC, 32 (25%) PACA, 24 (19%) PTCC, 17 (13%) GBCA, and 10 (8%) EHCC patients. The distribution is completely different from that reported in western countries. These cancers mainly occur in elderly patients. HTCC and GBCA were predominantly noted in female patients. Biliary cancers in Taiwan were not related to liver fluke infestation, inflammatory bowel disease or hepatitis B virus infection. However, a close association with biliary lithiasis was found. The incidence of gallstones was 67, 39, 20, 29 and 19% for PTCC, HTCC, EHCC, GBCA and PACA, respectively. The most common presentation for PTCC and GBCA was abdominal pain, or jaundice for HTCC, EHCC and PACA. These symptoms correlate well with the location of the tumors. Among serum tumor markers, the elevation of CA19-9 was most frequent, occurring in 86% of the patients while CA125 and CEA occurred in 47% and 30% of the patients, respectively. During the course of disease, infection developed in 61% of the patients and was the main cause of death in 25%. Biliary tract infection and sepsis were the two leading manifestations and occurred in 49% and 32% of the patients, respectively. Overall survival was poor except in patients whose tumor could be completely resected.
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PMID:A clinical study of 130 patients with biliary tract cancers and periampullary tumors. 896 Jan 45

To assess the impact of chronic viral hepatitis on host immune response, we analyzed the incidence of acute rejection and the frequency of infections in 86 patients infected with hepatitis B and C viruses and had developed clinical evidence of chronic liver disease and 1283 control patients who were transplanted at our center during the same period, but had no evidence of chronic viral hepatitis. To compare the mean number of rejections and the mean number of infections between the two groups, we used multivariate linear regression analysis, which allowed us to adjust simultaneously for the effects of 10 other risk variables with potential impact on graft rejection and posttransplant infection. During a mean follow up of 5.3+/-5.2 years, 62% of hepatitis patients and 54% of control patients had experienced an acute rejection (P=NS). The mean rejections/patient in the hepatitis group was 1.3+/-0.14 versus 1.03+/-0.03 in control (P=NS). In the linear regression analysis, the number of acute rejections in the hepatitis group was 0.16 higher than in control (P=NS). With reference to infection, 84% of hepatitis patients experienced an infectious complication in the posttransplant period, compared with 75% in the control (P=0.05). The mean number of infections/patient was 5.7+/-0.73 in the hepatitis group compared with 3.9+/-0.14 in the control group (P=0.002). The linear regression model had shown that the hepatitis group had a relative increase of 1.18 infections/pt, compared with control. Of the different sites of infection, the hepatitis group had a significant increase in bloodstream (0.48+/-0.08 vs. 0.25+/-0.02) P=0.003; pulmonary (0.60+/-0.09 vs. 0.38+/-0.03) P=0.03; and CNS infections (0.08+/-0.03 vs. 0.02+/-0.004) P=0.05 compared with control. Among the different microorganisms causing infection, the hepatitis patients had a significant increase in gram negative bacterial infections compared with the control group (74% vs. 61%) P=0.04. Our data suggest that chronic viral hepatitis is associated with a significant increase in overall infections, and that of potentially fatal infections involving CNS, lungs and bloodstream. Since there is no significant increase in the rate of graft rejection, one could consider a cautious reduction in the doses of maintenance immunosuppressive agents in renal transplant patients with chronic viral hepatitis. The reduced immunosuppression may in turn lower the death rate from sepsis and progressive hepatic failure.
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PMID:Chronic viral hepatitis enhances the risk of infection but not acute rejection in renal transplant recipients. 899 Mar 59

Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg. The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5). All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1). One child underwent retransplantation for hepatic artery thrombosis. Immunosuppression was by Cyclosporine A-based triple therapy in all cases. All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3). In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction. Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three. Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1). None of the babies experienced acute rejection. Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58). Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis. From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old.
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PMID:Hepatic transplantation in children under 3 months of age: a single centre's experience. 909 24


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