Cholestatic hepatitis after liver transplantation is associated with persistently high serum hepatitis C virus RNA levels.
Doughty AL. Spencer JD. Cossart YE. McCaughan GW.
A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, New South Wales, Australia.
Viral recurrence is universal after transplantation for hepatitis C infection. This may lead to difficulties in differentiating allograft dysfunction caused by chronic rejection from hepatitis C virus (HCV) recurrence. Cases of severe cholestatic hepatitis have also been reported in conjunction with reinfection of the graft with HCV. Patients receiving transplants for HCV-related liver disease were studied before and after transplantation by HCV RNA quantitation of serial serum samples. Four major clinical patterns of HCV recurrence could be distinguished posttransplantation: group 1, asymptomatic hepatitis with no significant symptoms; group 2, cholestatic hepatitis with centrilobular ballooning; group 3, hepatitis leading to chronic allograft rejection; and group 4, persistently normal serum aminotransferase levels. Pretransplantation viral load was shown to be an important indicator of disease severity because the group 2 patients had significantly higher pretransplantation viral loads than patients in group 1 (P = 0.01) and group 4 (P = 0.005). The group 2 patients also had persistently significantly higher posttransplantation viral loads than the patients in group 1 (P = 0.01) and group 4 (P = 0.02), whereas patients who developed chronic allograft rejection showed marked decreases in serum HCV RNA before retransplantation. Patients from group 4 had the lowest viral loads after transplantation. These results show that persisting graft cholestasis due to HCV is associated with persistently high HCV RNA levels compared with other etiologies of graft dysfunction. Prospective studies are needed to determine whether such quantitation may be diagnostically helpful in distinguishing the different patterns of HCV-related graft dysfunction observed after liver transplantation.
The influence of hepatitis C virus genotypes on the outcome of liver transplantation.
Vargas HE. Laskus T. Wang LF. Radkowski M. Poutous A. Lee R. Demetris JA. Gayowski T. Marino IR. Singh N. Dodson F. Casavilla A. Fung JJ. Rakela J.
Division of Gastroenterology, T.E. Starzl Transplantation Institute, University of Pittsburgh, PA 15213-2582, USA.
BACKGROUND: The aim of this study was to report the influence of hepatitis C virus (HCV) genotypes and HLA matches on the outcome of liver transplantation, hepatitis recurrence, and progression to cirrhosis after transplantation. METHODS: HCV genotypes were determined from pretransplantation sera and/or liver explant tissues from 202 patients with HCV-related end-stage liver disease. One hundred fifty patients with known infecting genotype for whom posttransplantation biopsy specimens were available or who had normal results of liver injury tests constituted the group analyzed. Patients were followed up for up to 4.5 years. Hepatitis activity index scores at the time of disease recurrence were used to assess disease activity. Cirrhosis was diagnosed by using histological evidence. The number of HLA matches with respect to A, B, DR, and DQ loci was determined. RESULTS: The rates of hepatitis recurrence were 25% and 75% at 1 year and 4 years, respectively; Kaplan-Meier survival analysis did not reveal significant differences between the infecting genotypes with respect to overall rates of survival or recurrence of hepatitis. At hepatitis recurrence, hepatitis activity index scores did not differ between the genotype groups. The distribution of infecting genotypes among the 7 patients who developed cirrhosis is reflective of pretransplantation distribution. Neither HLA site-specific nor total matches affected the rates of survival or disease recurrence. CONCLUSIONS: The infecting HCV genotype had no influence on the incidence or severity of recurrent hepatitis, rate of survival, or development of cirrhosis. HLA matching does not influence transplantation outcome for HCV-related disease.
Incidence, prevalence, and clinical outcome of hepatitis GB-C virus infection in liver transplant patients.
Kallinowski B. Buhrmann C. Seipp S. Goeser T. Stremmel W. Otto G. Theilmann L.
Department of Internal Medicine, University of Heidelberg, Germany.
A novel RNA virus of the Flaviviridae family has been discovered recently and designated hepatitis GB-C virus (GBV-C). Previous studies have reported that GBV-C is associated with posttransfusion hepatitis, chronic viral hepatitis, and cryptogenic hepatitis. However, the clinical significance of GBV-C infection has been questioned increasingly in patients not undergoing transplantation. To investigate whether GBV-C infection under immunosuppression affects the clinical or the histological outcome in liver transplant recipients, we determined the prevalence and incidence of GBV-C infections and the clinical and histological signs in patients after orthotopic liver transplantation (OLT). The presence of GBV-C was tested in sera from patients before and in regular intervals up to 6 years after OLT by nested reverse transcription-polymerase chain reaction using primers derived from the NS3 region. A total of 72 patients were studied. Before OLT, 8 of 72 (11.1%) patients were positive for GBV-C. After OLT, 7 of 8 (87.5%) remained positive. Of 64 patients who were negative for GBV-C before OLT, 23 became positive after OLT, resulting in a de novo rate of GBV-C infection of 35.9%. We could not detect a higher rate of histologically proven hepatitis in GBV-C-positive patients (29.1%) than in GBV-C-negative patients (14.6%, P > 0.057). Comparing GBV-C-positive with GBV-C-negative liver transplant patients, we could not find any differences in age, gender, liver function tests, number of blood transfusions, histological degree of hepatitis, or number of rejection episodes. Survival was not negatively influenced by GBV-C positivity. In conclusion, the presence of GBV-C did not influence the clinical or histological outcome in liver transplant patients.
Predictors of bile leaks after T-tube removal in orthotopic liver transplant recipients.
Shuhart MC. Kowdley KV. McVicar JP. Rohrmann CA. McDonald MF. Wadland DW. Emerson SS. Carithers RL Jr. Kimmey MB.
Department of Medicine, University of Washington, Seattle, USA.
Bile leaks after T-tube removal are a frequent cause of morbidity in orthotopic liver transplant recipients. The aim of this study was to determine factors that predict the development of these leaks in liver transplant recipients. Records of all patients who had undergone liver transplantation at the University of Washington Medical Center between January 1990 and September 1993 were reviewed. The following were excluded: patients with a Roux-en-Y anastomosis or inadvertent early T-tube removal and patients who died or underwent retransplantation before T-tube removal. All T-tube cholangiograms were reviewed blindly by two authors. Using logistic regression, several variables were assessed for possible association with bile leaks after T-tube removal; these included patient demographics, intraoperative variables, and clinical and cholangiographic variables related to T-tube removal. Of the 166 liver transplants performed in 150 patients, 99 transplants in 97 patients were evaluable for bile leak after T-tube removal. Thirty-three patients developed symptomatic bile leaks, and 21 underwent endoscopic or operative intervention for persistent symptoms. Only duct mural irregularities on the final cholangiogram were strongly associated with the development of a bile leak after T-tube removal (P = 0.001). In conclusion, bile leaks after T-tube removal occurred in one-third of patients undergoing orthotopic liver transplantation; the majority of these patients required some intervention. Duct mural irregularities were associated with bile leaks.
In vivo demonstration of impaired microcirculation in steatotic human liver grafts.
Seifalian AM. Chidambaram V. Rolles K. Davidson BR.
University Department of Surgery and Liver Transplantation, Royal Free Hospital School of Medicine, London, England.
The perfusion of human donor livers was studied during organ retrieval using laser Doppler flowmetry to assess the microcirculatory alteration caused by fatty infiltration (steatosis). Using a multichannel laser Doppler flowmeter, we measured the hepatic perfusion as flux units in 21 liver donors, eight of which were macroscopically fatty. Perfusion was recorded continuously for 2 minutes from two sites on each lobe at the beginning of organ retrieval, after the vascular dissection, and during sequential occlusion of the hepatic artery and portal vein. Mean flux value and SEM were calculated, and paired Student's t test was used for comparison between stages of perfusion. Multiple ANOVA was used to determine whether factors other than the normal or fatty parenchyma influenced the perfusion measurements. Mobilization of the graft did not affect parenchymal perfusion. Perfusion was significantly (P < 0.001) and rapidly reduced with hepatic artery or portal vein occlusion in both groups. Macroscopically steatotic livers (n = 8) had diminished microcirculation compared with normal livers (n = 13) (125 +/- 18 v 252 +/- 24 flux units; P = 0.002). Donors receiving inotropes (n = 10) had a lower mean perfusion rate (150 +/- 20 v 252 +/- 29 flux units; P = 0.026), but this effect was found in both the normal and steatotic groups with no interaction (ANOVA; P = 0.658). Steatosis diminishes the tissue perfusion in human liver grafts. Laser Doppler flowmetry may help identify grafts with a compromised microcirculation.
Diagnostic tools in the evaluation of patients with viral hepatitis undergoing liver transplantation.
Leon R. de Medina M. Schiff ER.
Center for Liver Diseases, University of Miami School of Medicine, FL 33136, USA.
Familiarity with the diagnostic parameters of viral hepatitis is imperative in the liver transplantation arena. Chronic viral hepatitis B and C are among the most common categories of end-stage liver disease. The preoperative diagnosis, determination of recurrent infection, and the assessment of antiviral therapeutic efficacy are dependent on appropriate virological testing. Furthermore, liver transplant personnel are at a high risk for parenterally transmitted viral hepatitis infection. Knowledge and understanding of the serological patterns of acute and chronic viral hepatitis, as well as recognition of the immune status for one or more of these viruses, will facilitate prevention and treatment of viral hepatitis for these health care providers.
De novo hepatitis B infection after liver transplantation: source of disease, incidence, and impact.
Fabia R. Levy MF. Crippin J. Tillery W. Netto GJ. Aguanno J. Dysert P. Goldstein RM. Husberg BS. Gonwa TA. Klintmalm GB.
Transplantation Services, Baylor University Medical Center, Dallas, TX 75246, USA.
New-onset hepatitis B (de novo B) after liver transplantation (OLTX) is an emerging concern. The goals of our study were to determine the incidence and pattern of this infection, to attempt determination of risk factors and the role of immunosuppression, and to review its morbidity/mortality. Over a 10-year period, 1078 OLTX were performed in 956 patients at our institution. Eight hundred twenty-six patients had proven negative hepatitis B surface antigen (HBsAg) before transplantation. Among these, 14 patients (1.7%), 8 women and 6 men, ages 21-59 years (median, 42 years), developed positive HBsAg after transplantation and were defined as de novo B. In 10 of 14 patients (71%), positive HBsAg was revealed during routine annual visits, whereas 4 patients had titer verification prompted by illness. Blood product use (cryoprecipitate, fresh-frozen plasma, platelets, and packed red blood cells) during the transplant hospitalization was similar between groups. Pretransplant hepatitis C infection was more prevalent among the 14 patients with de-novo B (7 of 14, 50% v 129 of 812, 16%; P < or = 05). Hepatitis B vaccine had been given to 12 patients (86%) (but not given to 2) who developed de novo B. Incidence and severity of rejection were similar in both populations, although de novo B patients had more late rejections. Our use of immunosuppressive protocols was the same in both groups. Mean follow-up of the infected patients is 24 (5-51) months. Twelve of these 14 de novo B patients were not clinically ill, with normal or near-normal transaminase levels. One of 14 has died from complications related to hepatic artery revascularization, and another is well after repeat OLTX for biliary strictures. Half of these de novo B patients remain free from viral antigens in their transplanted liver tissue. The high percentage of positive hepatitis C patients who acquire de novo B may indicate a link between these two viral infections and potential risk factor for de novo B. The origins of this infection are most likely multifactorial, needing further study. De novo B after liver transplantation is preliminarily associated with little clinical morbidity and mortality.
Is vaccination against hepatitis B infection indicated in patients waiting for or after orthotopic liver transplantation?
Chalasani N. Smallwood G. Halcomb J. Fried MW. Boyer TD.
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
It is a common practice to immunize patients against hepatitis B infection while they are waiting for liver transplantation, but the efficacy of this practice is unclear. This is a retrospective analysis of the antibody response to 20 microg of a recombinant hepatitis B vaccine in patients waiting for and after liver transplantation. The response to vaccination was measured 1-3 months after completion of the vaccination series. The risk of acquiring hepatitis B virus after liver transplant was determined by reviewing the results of tests for hepatitis B infection in 171 patients who underwent transplantation for non-hepatitis B diseases and who had not been vaccinated. Fifty-seven patients awaiting transplantation were eligible for the study, and a response to vaccination was observed in only 9 (16%). Patients with cholestatic liver disease had a significantly higher response (6 of 14; 43%) compared with noncholestatic liver disease (3 of 43; 7%; P = .004). Forty-five liver transplant recipients were immunized against hepatitis B after transplantation, and only 3 (6.7%) developed an antibody response. The frequency of posttransplant hepatitis B infection in the 171 patients who were not immunized and who lacked any evidence of hepatitis B infection pretransplantation was 4 of 171 (2.3%). The response rate to immunization with a recombinant hepatitis B vaccine in patients with chronic liver disease who are waiting for a liver transplant and after transplantation is poor. Given the poor response to vaccination and the low risk of acquiring hepatitis B virus after transplantation, centers need to reconsider the routine use of the hepatitis B virus vaccine in patients awaiting liver transplantation.
Small bowel bacterial overgrowth as a cause of chronic diarrhea after liver transplantation in children.
Mack DR. Dhawan A. Kaufman SS. Langnas AN. Seemayer TA.
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198-5160, USA.
Children who have undergone liver transplantation may develop chronic diarrhea for a number of reasons. Three children who underwent liver transplantation for liver failure, all of whom had had previous biliary and intestinal surgeries and whose postoperative course was marked by signs and symptoms of intestinal malabsorption including chronic diarrhea, are described. Duodenal aspirates showed a panoply of bacterial species, and duodenal histology featured villus atrophy in two: one associated with luminal gram-positive cocci and another with acute and chronic duodenitis. Oral antibiotics cleared the symptoms. Small bowel bacterial overgrowth may need to be considered in children with chronic diarrhea after liver transplantation, especially when previous intestinal surgery has taken place. Long-term antibiotic therapy may be required to effectively eradicate the offending organisms to suppress symptoms.
Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon.
Jain A. Demetris AJ. Manez R. Tsamanadas AC. Van Thiel D. Rakela J. Starzl TE. Fung JJ.
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center and the Veterans Administration Medical Center, Pittsburgh, PA 15213, USA.
Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-alpha often leads to allograft rejection. The aim of the present study was to determine if IFN-alpha therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-alpha was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-alpha with tacrolimus compared with control patients who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v controls 3.3 +/- 4.9 mg daily; P
Inflammatory process complicating giant hemangioma of the liver: report of three cases.
Pol B. Disdier P. Le Treut YP. Campan P. Hardwigsen J. Weiller PJ.
Department of Surgery, Hopital de La Conception, Marseille, France.
Three cases of giant hemangioma of the liver associated with clinical and laboratory signs of inflammatory process, including low-grade fever, weight loss, abdominal pain, accelerated erythrocyte sedimentation rate, anemia, thrombocytosis, and increased fibrinogen level with normal white blood cell count are described. One patient presented with slight cholestatic jaundice because of tumor-related bile duct compression, but the other two patients had normal liver function tests, except for a slight increase in gammaglutamyl transferase. Clinical and laboratory abnormalities disappeared after surgical excision. Inflammatory manifestations have rarely been reported during giant liver hemangioma. Intratumoral inflammation necrosis or bleeding could explain the symptoms but histological signs of inflammation were not detected in two of three surgical specimens. The release of immune mediators by liver endothelial cells lining the hemangioma is an alternative explanation. The incidence of inflammatory process complicating giant hemangioma is probably underestimated because our three cases were observed within a span of only 3 years.
Allograft rejection after liver transplantation for autoimmune liver diseases.
Hayashi M. Keeffe EB. Krams SM. Martinez OM. Ojogho ON. So SK. Garcia G. Imperial JC. Esquivel CO.
Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.
Autoimmune liver diseases (AILD) may progress to liver failure, requiring liver transplantation as definitive therapy, and these immune-mediated disorders may predispose the patient to more frequent graft rejection. The objective of this study was to determine the effect of preexisting AILD on the incidence of allograft rejection after liver transplantation. Sixty-three patients who underwent liver transplantation between March 1988 and December 1994 for AILDs that included autoimmune hepatitis (AIH; n = 33) and primary biliary cirrhosis (PBC; n = 30) were retrospectively compared with 47 patients who underwent liver transplantation for alcoholic cirrhosis during the same time period. There was a lower incidence of acute allograft rejection in patients with AILD who received tacrolimus-based compared with cyclosporine-based immunosuppression (50% v 85.5%; P = .02). However, patients with AILDs overall had a higher incidence of acute rejection than patients with alcoholic cirrhosis (81% v 46.8%; P < .001), regardless of the type of immunosuppression. In addition, steroid-resistant rejection occurred more frequently in patients with AILDs than in patients with alcoholic cirrhosis (38.1% v 12.8%; P = .003). There was also a trend toward a higher incidence of chronic rejection in patients with AILDs compared with patients with alcoholic cirrhosis (11.1% v 2.1%), but this difference did not reach statistical significance. Patient and graft survivals at 1 and 3 years were similar between patients with AILDs and alcoholic liver disease. Compared with alcoholic cirrhosis, preexisting AILDs are associated with a higher incidence of acute allograft rejection and a trend toward more frequent chronic rejection.
Percutaneous mesenteric venous thrombectomy and thrombolysis: successful treatment followed by liver transplantation.
Ryu R. Lin TC. Kumpe D. Krysl J. Durham JD. Goff JS. Everson GT. Kam I. Wachs M. Russ P. Shrestha R. Trouillot TE. Bilir BM.
Department of Interventional Radiology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Mesenteric vein thrombosis (MVT) is a rare cause of intestinal ischemia. Because of its nonspecific symptoms, diagnosis is often delayed. We describe a patient with liver cirrhosis who developed acute MVT while waiting for liver transplantation. Surgical intervention carried a high risk because of her underlying cirrhosis. Mesenteric venous thrombectomy and thrombolysis were performed with an AngioJet (Possis Medical, Minneapolis, MN) thrombectomy device and streptokinase infusion through transjugular route. The patient subsequently received an orthotopic liver transplant. We also present a review of the literature about the occurrence and treatment options for MVT.
Use of infrarenal conduits for arterial revascularization in orthotopic liver transplantation.
Muiesan P. Rela M. Nodari F. Melendez HV. Smyrniotis V. Vougas V. Heaton N.
Liver Transplant Surgical Service, King's College Hospital, London, England.
Arterial conduits that use donor iliac arteries represent a reliable technique for graft revascularization in orthotopic liver transplantation. We reviewed 757 consecutive liver transplantations performed between 1989 and 1995 for acute or chronic liver disease in adults and children. Of these, 218 patients received arterial conduits that used donor iliac arteries. The incidence of hepatic artery thrombosis (HAT) for conduits was 4.1% (9 of 218 patients) compared with 4% (22 of 539 patients) for direct arterial anastomosis. Patients in the arterial conduit group included 66% (99 of 159) of the children younger than 5 years of age, 75% (67 of 89) of all patients who underwent retransplantation, and, in particular, 25 patients regrafted for HAT. Arterial conduits provide an effective and reliable method of revascularization in patients at higher risk of arterial thrombosis. The actuarial 3-year patency rate for conduits is 95% and the incidence of HAT is similar to that in standard arterial anastomoses.
Cavoatrial shunt: a graft salvage procedure for suprahepatic caval anastomosis obstruction after liver transplantation.
Eid A. Rahamimov R. Ilan Y. Tur-Kaspa R. Berlatzky Y.
Department of Surgery and Transplantation, Hadassah University Hospital, Jerusalem, Israel.
A liver transplant recipient developed the Budd-Chiari syndrome because of an obstruction of the suprahepatic inferior vena cava anastomosis. Percutaneous balloon dilatation angioplasty was not feasible. On exploration, dense retrohepatic fibrotic reaction was observed. The patient underwent successful retrohepatic cavoatrial shunt placement by means of a 16-mm, ring-enforced polytetrafluoroethylene graft. We conclude that this shunt should be considered an additional graft salvage procedure for this complication.