The effect of immunosuppressive regimens on the recurrence of primary biliary cirrhosis after liver transplantation

Recurrence of primary biliary cirrhosis (PBC) has been described in liver transplant recipients. Type of immunosuppression has been reported to influence the frequency of recurrence. The aim of this study is to evaluate the occurrence and pattern of recurrent PBC in our liver transplant recipients and determine any association of immunosuppressive agents with its recurrence. Patients who underwent orthotopic liver transplantation (OLT) for PBC were identified from the University of Chicago Liver Transplant Database. Recurrent PBC was diagnosed based on specific pathological criteria. Of 46 patients who underwent OLT for PBC between 1984 and 2000, a total of 7 patients (15%) were diagnosed with recurrent PBC at a median of 78 months (range, 27 to 120 months) after OLT. Forty-three percent of patients were administered cyclosporine, whereas 57% were administered tacrolimus before disease recurrence. Rates of recurrence were not different between patients maintained on cyclosporine therapy (16%) compared with those maintained on tacrolimus therapy (18%; P = 1.0). There also was no difference in frequency of rejection episodes or duration of corticosteroid therapy between those who did and did not have recurrent PBC. In conclusion, recurrent PBC developed in a small number of patients 2 years or longer after OLT. In our population, there was no difference in recurrence rates between those administered cyclosporine or tacrolimus for immunosuppression. (Liver Transpl 2003;9:733-736.)     

Recurrent primary biliary cirrhosis: peritransplant factors and ursodeoxycholic acid treatment post-liver transplant.

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known.     

Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients

Orthotopic liver transplantation (OLT) is the only effective curative therapy for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent, although recent data have shown a recurrence rate of PBC of up to 32% after transplantation. The aim of this study is to investigate the course after disease recurrence, particularly with regard to liver function and survival in a long-term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations were performed in 1,415 patients at the Charité, Virchow Clinic. Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%) patients suffered from histologically proven PBC. Primary immunosuppression consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately after OLT, all patients received ursodeoxycholic acid. Corticosteroids were withdrawn three to six months after OLT. The median age of the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median survival time of 32 months. Two of these patients developed organ dysfunction owing to recurrence of PBC. Histological recurrence was found in 14 patients (14%) after a median time of 61 months (range 36-122 months). Patients with Tac immunosuppression developed PBC recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven patients developed an acute rejection and two patients a chronic rejection episode. Liver function did not alter within the first five yr after histologically proven PBC recurrence. Multivariate analysis of the investigated patients showed that the recipient's age and Tac immunosuppression were significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr after liver transplantation, owing to PBC, in addition to maintenance of liver function, shows excellent organ and patient survival rates. Although protocol liver biopsies revealed histological recurrence in 14 (14%) patients, only two patients developed graft dysfunction. Tac-treated patients showed more frequently and also earlier histologically proven PBC recurrence; however, in our population we could not observe an impact on graft dysfunction and patient's survival.     

肝移植治疗原发性胆汁性肝硬化的远期效果观察

目的 观察肝移植治疗原发性胆汁性肝硬化(PBC)的远期效果.方法 对15例接受了肝移植的终末期PBC患者进行长期随访,中位随访时间为70个月(38～86个月),记录并总结随访期间患者的相关资料,分析肝移植术后患者的预后、新发疾病以及术后远期存活率.结果 15例PBC患者共接受原位肝移植16例次,其中1例因原发性移植肝无功能进行了2次肝移植.术后患者均采用环孢素A(或他克莫司)+霉酚酸酯+激素的三联免疫抑制方案,部分患者使用了熊去氧胆酸.术后2周时,患者肝功能指标基本恢复正常,乏力、皮肤瘙痒及黄疸等症状缓解,患者的生存质量明显改善.术后有4例患者出现新发疾病(26.7%),1例为乙型肝炎病毒感染,2例为自身免疫性肝炎,1例为结肠癌,经治疗后2例好转,2例治疗无效死亡.肝移植术后,患者无PBC复发,1、2和5年的存活率分别为100%、100%和86.7%.结论 肝移植可提高终末期PBC患者的生存质量和存活率,但一些少见的新发疾病对患者的远期存活率影响较大.     

Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation.

The recurrence of primary biliary cirrhosis (PBC) in the hepatic allograft may impact patient and graft survival with long-term follow-up. The efficacy of ursodeoxycholic acid (UDCA) for treatment of recurrent PBC after liver transplantation (LT) remains less well known. The aims of this study were as follows: 1) to determine the significance of recurrent PBC on overall survival among PBC patients who underwent LT, and 2) to determine the efficacy of UDCA treatment after LT in patients with recurrent PBC. A retrospective cohort study was conducted of 154 PBC patients who underwent LT with at least 1 yr of follow-up after transplantation from 1985 through 2005. A total of 52 patients with recurrent PBC were identified. After adjusting for age and gender, recurrent PBC was not associated with death or liver retransplantation (hazard ratio, 0.97, 95% confidence interval, 0.41-2.31; P = 0.9). A total of 38 patients with recurrent PBC received UDCA at an average dose of 12 mg/kg/day for a mean duration of 55 months. Over a 36-month period, an estimated 52% of UDCA-treated patients experienced normalization of serum alkaline phosphatase and alanine aminotransferase compared to 22% of untreated patients. There was no significant difference in the rate of histological progression between subgroups. UDCA did not influence patient and graft survival. In conclusion, the development of recurrent PBC has little impact on long-term survival or need for retransplantation. While UDCA therapy is associated with biochemical improvement, its role in delaying histologic progression remains unknown. In this short period of treatment, UDCA was not associated with improved patient and graft survival compared to untreated patients.     

Hematologic aspects of liver transplantation for Budd-Chiari syndrome with special reference to myeloproliferative disorders

BACKGROUND: Patients who undergo orthotopic liver transplantation (OLT) for Budd-Chiari syndrome (BCS) traditionally have been anticoagulated with warfarin postoperatively. Because a significant proportion of BCS patients are found to have an underlying myeloproliferative disorder (MPD), antiplatelet therapy may be a more rational treatment strategy for this subgroup. METHODS: All patients who underwent OLT for the diagnosis of BCS at our institution through March 2000 were included in this analysis. Posttransplant therapy consisted of hydroxyurea and aspirin for those with MPDs. Standard anticoagulation or no antithrombotic treatment was given to BCS patients with other causes. Major posttransplantation complications (thrombosis and bleeding) and mortality were determined. RESULTS: Seventeen patients underwent OLT for BCS at our institution. The mean follow-up was 68.4 months. Two of seventeen patients died; one patient died of recurrent thrombosis (124 months after OLT) and the other patient died of acute hepatitis B (7 months after OLT). Twelve patients (71%) had evidence of a MPD. Two of the MPD patients were treated with warfarin before the initiation of hydroxyurea and aspirin therapy. The remaining 10 MPD patients were placed on only hydroxyurea and aspirin after OLT. Anagrelide was used in place of hydroxyurea in two patients because of cytopenias caused by the latter agent. The mean follow-up of this group of 10 patients was 59.9 months. Only one patient experienced recurrent thrombosis, which occurred more than 10 years after the original transplant. There were no major bleeding complications and posttransplant liver biopsies were well tolerated. CONCLUSIONS: Antiplatelet therapy that consists of hydroxyurea and aspirin is a safe and effective alternative to anticoagulation to prevent recurrent thrombosis in MPD patients with BCS after liver transplantation. For patients with a hypercoagulable state corrected by OLT, antithrombotic therapy probably is not required. For those patients with conditions not corrected by OLT or with idiopathic BCS, anticoagulation or other therapy to control the hypercoagulable state should be given.     

Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin

BACKGROUND: Recurrent hepatitis C virus (HCV) after liver transplantation (OLT) is a major cause of graft loss in HCV-positive patients. In this study, we evaluated the efficacy and safety of pegylated interferon alfa-2b (peginterferon) and ribavirin treatment for recurrent HCV after OLT and analyzed the influence of antiviral treatment on the histological course of recurrent hepatitis. METHODS: Twenty-five patients with recurrent HCV (genotype 1 n=20 and 2-4 n=5) received peginterferon (1 mg/kg/weekly) and ribavirin (600 mg) for 48 weeks. Viral load prior to treatment was below 1,000,000 (IU/ml) in 11 of 25 patients. Sustained antiviral response was defined as undetectable HCV-RNA in serum 6 months after stopping of therapy. All patients underwent liver biopsy prior to treatment and after 72 weeks. RESULTS: Seventeen of 25 patients became HCV-RNA-negative after treatment (68%). Sustained virologic response (SVR) was achieved in 9/25 (36%) patients. Liver specimen showed increase of fibrosis from 1.7 to 2.0 within 72 weeks. Side effects like neutropenia (60%) and anemia (36%) were treated with G-CSF, erythropoietin, and dose reduction of peginterferon and ribavirin. CONCLUSIONS: The use of peginterferon is safe and effective in patients with recurrent HCV. Treatment of side effects, especially neutropenia or anemia, helped to maintain antiviral therapy. Despite a viral response of 68% during treatment, the patients showed further progress of recurrent hepatitis in liver specimen.     

Caroli disease patients have excellent survival after liver transplant

BackgroundCaroli disease (CD) is characterized by dilation of the intrahepatic biliary tree, which may result in malignancy. Treatments include management of symptoms and hepatic resection to decrease disease burden. In patients with CD not amenable to these treatments, orthotopic liver transplantation (OLT) has been used. This study examines if OLT is a reasonable treatment for patients with CD.Materials and methodsThe United Network of Organ Sharing/Organ Procurement and Transplantation Network database between September 30, 1987 and March 31, 2011 was queried. Cases without patient or allograft survival time or without a diagnosis were excluded from analysis. Patients with CD were compared to patients with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was performed by log-rank test and Kaplan-Meier.ResultsOne hundred forty patients with CD were compared to 4797 patients with PBC, 489 patients with secondary BC, 6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%, 80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have significantly improved patient and allograft survivals after OLT compared to patients with secondary BC (P = 0.003, P = 0.015) and all other patients undergoing OLT (P = 0.003, P = 0.026). There is a trend towards long-term improved patient and allograft survival in transplanted patients with CD compared to patients with PBC and PSC.ConclusionsThese results suggest that OLT should be considered an effective treatment modality for patients with CD resulting in excellent long-term outcomes.     

Recurrence of primary sclerosing cholangitis after liver transplantation

Orthotopic liver transplantation (OLT) has become the only effective therapeutic option for patients with end-stage liver disease caused by primary sclerosing cholangitis (PSC). Excellent long-term outcome has been reported, with 5-year patient survival rates of approximately 80%. In the last few years, increasing evidence has emerged that PSC recurs after OLT. The diagnosis of PSC is based on well-defined cholangiographic features combined with biochemical and histological findings. However, none of these features is specific for PSC, particularly after OLT, because biliary strictures in the liver allograft can occur from a variety of causes other than recurrence. Therefore, PSC recurrence remains a controversial issue, especially because of a lack of a gold standard for diagnosis and well-established diagnostic criteria. Some reports provided cholangiographic evidence that post-OLT biliary strictures occurred more frequently in patients with PSC than in those who underwent OLT for other liver diseases (including patients with a Roux-en-Y biliary reconstruction). Because no other possible cause of biliary strictures could be invoked to explain the greater prevalence of these strictures, recurrent disease has been implicated. There also is histological evidence suggesting that PSC recurs after OLT. Histological findings suggestive of PSC were found more often in PSC allografts compared with a control group. Furthermore, histological features typical for PSC (fibro-obliterative lesions) were seen exclusively in liver biopsy specimens from patients with PSC. Recurrence of PSC was defined in a recent study from the Mayo Clinic by means of strict cholangiographic and histological criteria in a large cohort of patients with PSC in whom other causes of biliary strictures were excluded. PSC recurrence was found in 20% of patients. No risk factor for PSC recurrence could be found, and recurrent disease did not influence patient or graft survival after a mean follow-up of 4.5 years. In conclusion, several studies provided convincing evidence that PSC recurs after OLT, with an incidence of 5% to 20% and an interval to diagnosis of at least 1 year after OLT. To date, patient and graft survival do not appear to be negatively affected by disease recurrence in the intermediate term of follow-up. (Liver Transpl 2002;8:575-581.)     

Recurrence of primary biliary cirrhosis after liver transplantation: Histologic estimate of incidence and natural history

The goals of this study were to determine the rate of recurrent primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT) based on strict morphologic criteria and to evaluate histologic progression of recurrent PBC over time. Strict criteria for PBC recurrence were established as the presence of a florid duct lesion or destructive lymphocytic cholangitis within a dense portal infiltrate. Of the 784 OLTs performed at the Mayo Clinic during the first 12 years of the program, 100 met criteria for the PBC study group, and 35 met criteria for the control group. Strict histologic criteria for recurrent PBC were observed in 17 of 100 (17%) study patients (14 with florid duct lesion, 3 with destructive lymphocytic cholangitis within dense portal infiltrate). Mean follow-up for the PBC group was 4.7 years (range, 1.0 to 13.8). Mean time to recurrence was 3.7 years (median, 3.1; range, 0.3 to 7.9). In those who met strict criteria for recurrent PBC, 2 of 17 progressed to septal fibrosis (stage 3). No florid duct lesions, destructive lymphocytic cholangitis, or septal fibrosis were observed in the control group. Other less specific morphologic features of PBC (portal infiltrates, plasma cells, dense lymphoplasmacytic infiltrates, and lymphocytic cholangitis) were also evaluated in the course of this study. Based on strict criteria, a conservative histologic estimate of the rate of recurrent PBC is 17% with a mean of 4.7 years of follow-up. When criteria for histologic recurrence are expanded to include moderate lymphocytic cholangitis with lymphoplasmacytic portal infiltrate, the recurrence rate of PBC is estimated as 26%. (Liver Transpl 2003;9:1086-1093.)     

Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.     

Liver transplantation for primary biliary cirrhosis: A long-term pathologic study

Although recurrent primary biliary cirrhosis (PBC) after liver transplantation (LT) has been reported, the full spectrum of changes and progression to fibrosis and cirrhosis is not yet established. We performed a detailed retrospective clinicopathologic analysis of 43 patients who underwent LT for PBC. Eight patients (18.6%) had definite recurrent PBC with florid duct lesions, 5 patients (11.6%) had recurrence with features of autoimmune liver disease, not otherwise specified (AILD-NOS), 7 patients (16.3%) had plasmacytosis only, 4 patients (9.3%) had chronic rejection, 18 patients (41.9%) have no recurrence at present, and 1 patient (2.3%) had acquired hepatitis C. Although definite diagnoses of PBC and AILD-NOS recurrences (n = 13) were made 1 month to 14 years (median, 4 years) post-LT, all patients had plasmacytosis in their earlier biopsy specimens. Also, these patients showed similar pre-LT and post-LT clinical features, with progressive fibrosis in 4 of 8 and 2 of 5 patients, respectively. Four of 13 patients with definite recurrence and 14 of 18 patients with no recurrence were administered azathioprine (AZA) as part of their post-LT therapy (P = .01). Six of 13 and 16 of 18 patients currently are alive, with median follow-ups of 11 and 5 years, respectively. No significant differences were seen with donor-recipient group A, group B, group O blood type, sex, or HLA mismatches; native liver histological characteristics; or tacrolimus-based therapy. In conclusion, recurrent autoimmune liver disease was seen in 30% of patients after LT for PBC and had features of PBC and/or AILD-NOS. Progression seen in 46% of patients was associated with late graft failure. Patients with no recurrent disease had shorter follow-up periods and more frequent immunosuppression, including AZA; some may still develop recurrence with longer follow-up. (Liver Transpl 2003;9:87-96.)     

De novo cryptogenic hepatitis after sustained eradication of hepatitis C following liver transplantation

Patients with recurrent hepatitis C (HCV) after liver transplantation (OLT) are often treated with interferon and ribavirin in an attempt to eradicate HCV and prevent cirrhosis. We report four patients who developed de novo cryptogenic hepatitis following sustained eradication of recurrent HCV, which led to decompensated liver disease in two patients, both of whom required listing for retransplantation. Between September 2000 and October 2001, 38 consecutive patients with recurrent HCV were treated with interferon alpha 2b and ribavirin, of whom eight patients (21%) developed a sustained response to HCV eradication. Four of these patients developed cryptogenic hepatitis, which led to decompensated cirrhosis in two patients. Both patients were listed for retransplantation but died on the waiting list. No etiology for liver disease was identified despite extensive investigations in all four patients including postmortem analysis in the two patients. We hypothesize that these individuals developed an aberrant immune response leading to allograft injury whose severity may be determined by underlying haplotype, degree of immunosuppression, presence/absence of HCV, and duration of treatment. We have not found any similar reports in the literature but anticipate more cases to be reported given the universal use of antiviral therapy for recurrent HCV.     

De novo autoimmune hepatitis in Korean children after liver transplantation: a single institution's experience

Introduction

De novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) has been described as a new type of late graft dysfunction in children who have not undergone transplantation for previous autoimmune liver disease. The purpose of this study was to evaluate the clinical aspects of de novo AIH among children following OLT.

Patients and Methods

Between January 1994 and May 2007, 149 children underwent OLT, including 1 with recurrent AIH who was excluded from this study, whereas 4 others developed de novo AIH (2.7%; n = 4/148). We analyzed the demographics, laboratory characteristics, and response to treatment of the 4 children with de novo AIH following OLT.

Results

The 4 patients were all girls with a median interval after OLT to presentation of 6.5 years (range, 0.7-8.8 years). The median age when de novo AIH developed was 12.4 years (range, 8.7-17.3 years). All cases were detected by abnormal liver function tests, namely, increased aspartate aminotransferase (AST; median, 322 IU/L; range, 181-919 IU/L). One patient showed elevated immunoglobulin G. Three patients displayed positive antinuclear antibodies. All were seronegative for smooth muscle antibody and liver-kidney microsomal type 1 antibody. One patient showed anti-mitochondrial antibody. All patients were treated with steroids with or without azathioprine. The liver function tests in these 4 patients, improved by at least 50% during the first month of treatment, responding to steroid treatment with or without azathioprine.

Conclusion

In preadolescent or adolescent female patients with unexplained graft dysfunction after OLT, it is important to recognize de novo AIH rapidly and to develop an adequate diagnostic strategy, including evaluation of serum autoantibodies, immunoglobulin G, and liver biopsy.     

Experiences in liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Beside surgical resection, orthotopic liver transplantation (OLT) is not only effective but also the only potentially curable treatment in selected cases of small tumors. We report our experience in 11 male patients transplanted for HCC from August 1998 to July 2002. Selection criteria for OLT were unresectability of the hepatic tumor and severity of the underlying liver disease. The tumor diagnosis was confirmed by histology, imaging techniques, and tumor markers. All patients received an orthotopic liver allograft using a modified piggyback technique. Six of the 11 patients are alive; one died due to acute rejection and four died from recurrent disease. In all four patients with recurrent disease, vascular invasion was shown histologically, whereas only one patient without evidence of recurrence showed vascular invasion. To prevent recurrence after OLT the immunosuppressive regime was adjusted to the underlying disease by early cessation of prednisolone and reduction in the long-term exposure to immunosuppressive drugs. Patients were screened for recurrence by ultrasound and computed tomography. Recurrent HCC were treated symptomatically. OLT is an effective treatment for subgroups of patients with HCC. It might be possible to downstage the liver tumor by chemoembolization and/or radiofrequency ablation and allow the patients to wait for a suitable donor. After OLT the early withdrawal of prednisolone and the reduction of other immunosuppression is feasible. In conclusion, OLT can be a potentially curative therapy for HCC.     

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.     

Repeat Liver Resection for Hepatocellular Carcinoma Complicating Primary Biliary Cirrhosis

The incidence of hepatocellular carcinoma (HCC) complicating primary biliary cirrhosis (PBC) is between 0.7% and 16%. Repeat liver resection for recurrent HCC complicating PBC is not usually performed and not published because this approach is not generally applicable due to liver dysfunction. We applied repeat liver resection for these diseases. Three patients were diagnosed with PBC. The first HCC was noted at a mean of 6 years (4–17 years) after diagnosis of PBC. The second HCC occurred at a mean of 2.5 years (0.4–3 years) after the first surgery. All patients were treated with curative resection on first and second surgery. The mean overall survival time after the first liver resection was 46 months. Repeat liver resection for recurrent HCC complicating PBC is an option and may improve the outcome.     

Low risk of hepatitis B virus recurrence after withdrawal of long-term hepatitis B immunoglobulin in patients receiving maintenance nucleos(t)ide analogue therapy.

Hepatitis B virus (HBV) recurrence rates of 0-16% had been reported in patients maintained on nucleoside analogues (NA) after hepatitis B immunoglobulin (HBIG) discontinuation after orthotopic liver transplantation (OLT). However, follow-up in most studies was short. We aimed to determine the long-term risk of HBV recurrence using this strategy. All HBV patients who received > or =7 doses of intravenous HBIG after OLT, with no HBV recurrence while receiving HBIG, and who eventually discontinued HBIG and were maintained on NA, were included. HBV recurrence was defined as HBsAg-positive or HBV DNA > or =5 log copies/mL on 2 consecutive occasions. Twenty-one patients met the inclusion criteria. Immediate post-OLT prophylaxis was combination HBIG and NA in 15 patients, whereas 6 patients received HBIG monotherapy for 62-109 months before NA was added. HBIG was discontinued a median of 26 (range, 0.2-121) months after OLT. Median follow-up post-HBIG discontinuation was 40 (range, 5-51) months. Only 1 patient, who had 12 months of HBIG and was noncompliant to NA therapy, had HBV recurrence, 34 months after HBIG discontinuation. One patient had HBV DNA of 3.3 log copies/mL 47 and 48 months after HBIG discontinuation but remained HBsAg-negative. Lamivudine-resistant mutations were detected in both patients. Probability of HBV recurrence was 0% and 9% at 2 and 4 years after HBIG discontinuation. Three patients had 1-2 episodes of transiently detectable HBV DNA. All were HBV DNA and HBsAg negative on repeated tests over a period of 2-36 months. Maintenance therapy with NA after discontinuation of long-term HBIG therapy is associated with a low risk of HBV recurrence after OLT in compliant HBV patients.     

Primary liver disease as a determinant for acute rejection after liver transplantation

Background: Graft rejection and infection remain major problems following liver transplantation; both are heavily influenced by the immunosuppressive regimen. Despite the disparity in the primary disease leading to transplantation, all patients receive the same post-transplant immunosuppressive treatment in a given center. The aim of this study is to detect a possible effect of the underlying disease on the incidence of early acute rejection episodes after orthotopic liver transplantation (OLT). Patients and Methods: Retrospective analysis on all 101 consecutive liver transplants performed in 95 patients between 1983 and March 1998; five of these patients, surviving less than 30 days, were not included. The immunosuppressive regimen was based on conventional triple therapy during the whole study period. The diagnosis and treatment of acute rejection within the first 30 days post-OLT was uniform throughout the whole study period. Results: Though there were no differences with respect to patients' characteristics [age, child classification, number of HLA-mismatches or cytomegalovirus (CMV)-serocompatibility], patients with primary biliary cirrhosis (PBC) showed a significant increase of acute rejection after OLT compared with the other patients transplanted for other liver diseases (P = 0.024). The incidence of infection was not elevated in patients transplanted for PBC when compared with other diagnoses. Conclusion: Our results indicate that primary liver disease may be a determinant for acute graft rejection in PBC. Furthermore, these results suggest that immunosuppressive regimens based on the underlying disease should be considered. Received: 19 October 1998 Accepted: 28 January 1999     

Acquired hepatocerebral degeneration in a patient with HCV cirrhosis: complete resolution with subsequent recurrence after liver transplantation.

Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a chronic brain disorder caused by liver dysfunction and long-standing portal-systemic shunting. It typically presents with dysathria, ataxia, tremor, involuntary movements and altered mental status, and often does not respond to conventional medical therapy for hepatic encephalopathy. There is scarce and conflicting information regarding the clinical course of AHD after liver transplantation (OLT). We present a case of a 47-year-old woman with hepatitis C (HCV) cirrhosis who developed severe manifestations of AHD after multiple bouts of hepatic encephalopathy. Her first OLT was complicated with primary nonfunction requiring immediate retransplantation. The second OLT led to complete clinical and radiological resolution of the AHD. However the patient developed recurrence of AHD 11 months post-transplant due to recurrent HCV and chronic rejection leading to cirrhosis of the graft. The patient developed severe neurological symptoms, despite mild synthetic graft dysfunction. A third OLT led again to disappearance of the clinical and radiological manifestations of AHD. AHD may show complete resolution after OLT; however it may rapidly recur following recurrent liver disease or graft dysfunction.