Transplantation For Primary Biliary Cirrhosis Research Articles

The long-term outcomes of deceased-donor liver transplantation for primary biliary cirrhosis: a two-center study in China

Background & AimsFactors that influence the outcomes after deceased-donor liver transplantation (DDLT) for primary biliary cirrhosis (PBC) are not well known. We aimed to clarify these effects on the outcomes after DDLT.MethodsWe retrospectively analyzed patients with PBC who underwent DDLT from March 2006 to July 2018 at the organ transplantation center of the First Hospital of Jilin University and the First Central Hospital of Tianjin. Changes in liver function were assessed posttransplantation. Recurrence, survival rate, and complications were recorded at follow-up. The effect of liver transplantation on survival and recurrence was evaluated using univariate and/or multivariate Cox regression analyses.ResultsIn total, 69 patients with PBC undergoing DDLT were included in this study. At 4 weeks posttransplant, all liver function tests were normal. During a median follow-up time of 32 months, 5-year overall survival and recurrence rates were estimated as 95.1% and 21.8%, respectively. A recipient aspartate aminotransferase-to-platelet ratio index (APRI) greater than 2 was negatively associated with survival (P = 0.0018). Multivariate regression analysis demonstrated that age younger than 48 years was an independent risk factor for recurrent PBC in recipients undergoing liver transplantation (hazard ratio 0.028, 95% confidence interval 0.01–0.71, P = 0.03). Posttransplant infections (62%) and biliary tract complications (26%) were the most common complications.ConclusionLiver transplantation is an effective treatment for patients with PBC. Liver function normalizes by 4 weeks posttransplant. Although posttransplant survival rate is high, recurrence is possible. To some extent, survival rate and recurrence rate can be predicted by APRI and age, respectively.

Long-Term Outcomes of Living-Donor Liver Transplantation for Primary Biliary Cirrhosis: A Japanese Multicenter Study.

The factors that influence long-term outcomes after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC) are not well known. Compared with deceased-donor transplantation, LDLT has an increased likelihood of a related donor and a decreased number of human leukocyte antigen (HLA) mismatches. To clarify the effects of donor relatedness and HLA mismatch on the outcomes after LDLT, we retrospectively analyzed 444 Japanese patients. Donors were blood relatives for 332 patients, spouses for 105, and "other" for 7. The number of HLA A-B-DR mismatches was none to two in 141, three in 123, and four to six in 106 patients. The 15-year survival rate was 52.6%, and PBC recurred in 65 patients. Recipient aged 61 years or older, HLA mismatches of four or more (maximum of six), graft:recipient weight ratio less than 0.8, and husband donor were adverse indicators of patient survival. IgM 554 mg/dL or greater, donor-recipient sex mismatch, and initial immunosuppression with cyclosporine were significant risks for PBC recurrence, which did not affect patient survival. In subgroup analysis, conversion to cyclosporine from tacrolimus within 1 year diminished recurrence. Prospective studies are needed to determine the influence of pregnancy-associated sensitization and to establish an optimal immunosuppressive regimen in LDLT patients.

Recurrent disease after liver transplantation for primary biliary cirrhosis and primary sclerosing cholangitis

Recurrent disease after liver transplantation for primary biliary cirrhosis and primary sclerosing cholangitis

Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence

Recurrence of primary biliary cirrhosis (PBC) after liver transplantation (LT) is not rare and can occasionally lead to severe graft dysfunction and retransplantation. Ursodeoxycholic acid (UDCA) is a safe and effective treatment for PBC. However, whether preventive administration of UDCA after LT could lower the incidence of PBC recurrence is unknown. Patients transplanted for PBC in five French and Swiss centers from 1988 to 2010 were included. Most patients from a single center received UDCA (10-15 mg/kg/d) preventively. Recurrence of PBC was histologically defined from biopsies routinely performed at 1, 5, 10, and 15 years of follow-up, and at any time when clinically indicated. A total of 90 patients with a 1-year minimum follow-up were studied retrospectively, including 19 (21%) patients receiving preventive UDCA. The mean follow-up was 12 years. Recurrence was diagnosed in 48 (53%) patients. The recurrence rates at 5, 10, and 15 years were 27%, 47%, and 61%, respectively. In a multivariate proportional hazards model adjusted for potential confounders and risk factors, preventive UDCA was the only factor affecting the risk of recurrence significantly (HR=0.32; 95% CI: 0.11-0.91). The 5, 10, and 15-year rates of recurrence were 11%, 21%, and 40%, respectively, under preventive UDCA, and 32%, 53%, and 70%, respectively, without preventive UDCA. Seven patients with recurrence (15%) progressed to cirrhosis, requiring retransplantation in one. However, neither recurrence nor preventive UDCA had a significant impact on survival. Preventive treatment with UDCA reduces the risk of PBC recurrence after LT.

Relevance of male-to-female sex mismatch in liver transplantation for primary biliary cirrhosis.

Because male-to-female transplantations are related to exposure to H-Y antigen, sex matching may influence the outcomes after liver transplantation for autoimmune diseases. The purpose of this retrospective study was to evaluate the relevance of male-to-female mismatch in liver transplantation for primary biliary cirrhosis (PBC). This retrospective study was based on the data of 82 female liver transplant recipients with PBC from a single institution. The primary outcome measure was graft survival at 10 years. The negative effects of well-known risk factors for poor outcomes were evaluated separately and compared between the female-to-female and male-to-female transplantations. Graft survival was similar after female-to-female and male-to-female transplantations (74.7% versus 73.1% at 10 years, respectively, p=0.676). Regarding the differential impact of other risk factors, prolonged cold ischemia and increased amount of blood transfusions adversely influenced outcomes after male-to-female transplantation (p=0.039 and p=0.039, respectively) but not after female-to-female transplantation (p=0.843 and p=0.110, respectively). Sex mismatched transplantations were associated with lower 10-year graft survival in subgroups of patients with blood transfusions >4 units (61.4% versus 100.0%, p=0.063) and >8 hours of cold ischemia (54.7% versus 75.8%, p=0.418). Although male-to-female sex mismatch does not seem to yield a direct negative impact on outcomes following liver transplantation for PBC, it can aggravate the negative effects of prolonged cold ischemia and blood transfusions.

Chronic Immune-Mediated Reaction Syndrome as the Cause of Late Graft Mortality in Living-Donor Liver Transplantation for Primary Biliary Cirrhosis

IntroductionFew studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC). Patients and MethodsFifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed. ResultsThe 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from “chronic immune-mediated reaction syndrome,” showed reciprocal changes over time. No patient died of recurrent PBC. ConclusionsMale donor and ≥4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC.

Liver transplantation for primary biliary cirrhosis

Liver transplantation for primary biliary cirrhosis

Disease recurrence plays a minor role as a cause for retransplantation after living‐donor liver transplantation for primary biliary cirrhosis: A multicenter study in Japan

To clarify the role of disease recurrence as a cause of graft loss after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), we investigated explant grafts, as well as the native liver and liver biopsy specimens, of patients who underwent retransplantation. Of 516 patients who underwent LDLT for PBC and were registered in the Japanese Liver Transplant Registry, nine patients (1.7%) underwent retransplantation. Seven patients undergoing retransplantation later than 6 months after primary liver transplantation (LT) were enrolled. All seven patients were female, with ages ranging from 34-57 years, and Model for End-Stage Liver Disease scores ranging 10-28. The right lobe was used as graft in one and the left lobe in six. The initial immunosuppression regimen was tacrolimus in six and cyclosporin in one. The period between the primary LT and retransplantation ranged 11-120 months, with a median of 36 months. Three patients survived and four patients died due to poor graft functions or complications after retransplantation. The primary causes of primary graft loss revealed by histological examination of the explant livers were chronic rejection in three, portal thrombus and/or steatohepatitis in three and outflow block in one. PBC recurrence was observed in 3 and the stage was mild in all. PBC recurrence has a small impact as a cause of graft loss after LDLT.

Long-term outcome of living donor liver transplantation for primary biliary cirrhosis

In living donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), the majority of donors are genetically related to their recipients, leading to concerns of an earlier recurrence of PBC and a poorer prognosis due to genetic susceptibility. Totally 81 patients who underwent LDLT for PBC were the subjects of the present study. Immunosuppressive agents consisted of tacrolimus and methylprednisolone. In the outpatient clinic, when the aspartate and alanine aminotransferase level exceeded the upper limit of the normal range, the dose of methylprednisolone was increased from 4 to 6 mg/day for several months. Blood was examined every 2 weeks for 3 months and a liver biopsy was performed when aminotransferase levels did not decrease to the upper limit of the normal range after more than 3 months. Five-year survival and recurrence rates were estimated and the prognostic factors were analyzed. The mean observation period was 6.2 years. Five years after LDLT for PBC, the biopsy-proven PBC recurrence rate was 1%. The 5-year patient survival rate was 80%. The nonrelated or blood-related donor factor and number of human leukocyte antigen matches did not correlate with prognosis. PBC recurrence rate after LDLT in our series was lower than that in previous studies.

Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single-center Asian experience

From March 1984 to November 2008, we performed 539 primary liver transplantations (LTs). Nineteen (19, 3.5%) were transplanted for end-stage liver disease secondary to primary biliary cirrhosis (PBC). There were 17 (89%) female and 2 (11%) male recipients. The overall mean age was 50.3 ± 6.3 yr. The mean model for end-stage liver disease, and Child-Turcotte-Pugh scores were 20.7 ± 2.1, and 11.0 ± 0.5, respectively. There were 2 (11%) United Network for Organ Sharing status 3, 16 (84%) 2B, and 1 (5%) 2A patients. Fourteen patients (14, 73.7%) underwent living donor LT, and five patients (26.3%) received deceased donor LT. The primary immunosuppression consisted of cyclosporine (n = 5) and tacrolimus (n = 14). Liver function returned to normal one month after transplantation. The overall mean follow-up was 5.8 ± 0.8 yr (range, four months to 15.7 yr). The overall one-, three-, and five-yr survival rates were 94.7%, 89.2%, and 89.2%, respectively. Without hepatitis B virus (HBV) prophylaxis, one patient acquired de novo HBV infection after receiving a graft from an anti-HBc(+) donor. Another patient developed recurrent hepatitis C infection and expired 25 months after transplantation. Our results showed that HBV prophylaxis was effective not only against de novo infection, but it also worked on pre-transplant HBV carrier with PBC and helped in virus clearance.

Lessons Learned from Liver Transplantation with the Canadian First Nations

Lessons Learned from Liver Transplantation with the Canadian First Nations

Anti-mitochondrial antibodies: what’s new?

<h3>Introduction</h3> The method of choice for anti-mitochondrial antibody detection has been indirect immunofluorescence (AMA-IIF) on fresh frozen sections of rodent liver, kidney and stomach with an accepted sensitivity of between 90 and 95%. However, primary biliary cirrhosis (PBC) is a disease of variable prognosis and up to now there have been no assays that have been able to predict patients who are more likely to progress to liver failure. Recently, a line blot assay has become available (EUROIMMUN) that utilises both native PDC and the recombinant ‘triple' E2 subunit antigen M2-3E in addition to PBC-specific anti-nuclear antigens (ANAs), gp210 (nuclear pore), Sp100 (multiple nuclear dots) and PML (promyelocytic leukaemia nuclear bodies). <h3>Aim</h3> To investigate the performance of this assay in identifying patients with clinical PBC and to investigate the performance of this assay in identifying patients who are more likely to progress to more severe PBC based on profiling reactivities to M2, M2-E3 and the PBC-specific ANAs. <h3>Patients</h3> Patients included 48 consecutive AMA-IIF positive patients detected during routine autoantibody investigation, 37 patients being followed up in specialist gastroenterology clinics for PBC and 49 patients receiving a liver transplant for PBC. <h3>Results</h3> A review of the available clinical, biochemical and biopsy data on the 48 consecutive AMA-IIF positive patients found that patients who were anti-M2 and anti-M2-E3 positive were more likely to have clinical PBC at the time of testing, <i>p</i> ≤ 0.005 compared to those who were anti-M2/M2-E3 negative. These results were confirmed when all three groups were compared. The frequency of anti-M2 and anti-M2-E3 positivity was significantly higher in the PBC transplant group, <i>p</i>=0.0025 compared to the two groups. The frequency of anti-gp210 was also significantly higher in the PBC transplant group, <i>p</i>=0.026, supporting previous reports that anti-gp210 appears to be a significant risk factor for hepatic failure in PBC patients. We also confirmed that anti-Sp100 positivity was not clinically important in PBC patients. However, the frequency of anti-PML positivity was higher in the PBC transplant group. <h3>Conclusion</h3> We conclude that testing for anti-M2, anti-E3, anti-gp210 and anti-PML may be useful in identifying PBC patients who are at greater risk of disease progression.

Trends in liver transplantation for primary biliary cirrhosis in the Netherlands 1988-2008

BackgroundA decrease in the need for liver transplantations (LTX) in Primary Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid (UDCA), has been reported in the USA and UK. The aim of this study was to assess LTX requirements in PBC over the past 20 years in the Netherlands.MethodsAnalysis of PBC transplant data of the Dutch Organ Transplant Registry during the period 1988-2008, including both absolute and proportional numbers. The indication for LTX was categorized as liver failure, hepatocellular carcinoma or poor quality of life (severe fatigue or pruritus). Data were analysed for two decades: 1.1.1988-31.12.1997 (1st) and 1.1.1998-31.12.2007 (2nd). The severity of disease was quantified using MELD scores. To fit lines which show trends over time we applied a linear regression model.ResultsA total of 110 patients (87% women) was placed on the waiting list. 105 patients were transplanted (1st: 61, 2nd: 44), 5 (5%) died while listed. The absolute annual number of LTX for PBC slightly decreased during the 20 year period, the proportional number decreased significantly. At the time of LTX the mean age was 53.6 yrs. (1st: 53.4, 2nd: 53.8), the mean MELD score 13.9 (1st:14.5, 2nd:13.0). The median interval from diagnosis to LTX was 90.5 months (1st:86.5, 2nd: 93.5). 69% of patients was treated with UDCA (1st 38%, 2nd 82%).ConclusionsOver the past 20 years the absolute number of LTX for PBC in the Netherlands showed a tendency to decrease whereas the proportional decrease was significant. There was a trend over time toward earlier transplantation.

Cyclosporine A Protects Against Primary Biliary Cirrhosis Recurrence After Liver Transplantation

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end-stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44-16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89-14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05-0.35, p < 0.001 and HR 0.27, 95% CI 0.11-0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06-0.71, p = 0.02). Five-year probability of survival was 83% and 96%, in patients without and with recurrence (log-rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long-term patient survival.

Primary liver transplantation for autoimmune hepatitis: A comparative analysis of the European Liver Transplant Registry

The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.67-0.77]. This was similar to that of patients undergoing transplantation for alcoholic cirrhosis (0.74, 95% CI = 0.72-0.76, n = 6424) but significantly worse than that of patients undergoing transplantation for PBC (0.83, 95% CI = 0.80-0.85, n = 1588). Fatal infectious complications occurred at an increased rate in patients with AIH (hazard ratio = 1.8, P = 0.002 with PBC as the reference). The outcome of pediatric AIH patients was similar to that of adult patients undergoing transplantation up to the age of 50 years. However, the survival of AIH patients undergoing transplantation beyond the age of 50 years (0.61 at 5 years, 95% CI = 0.51-0.70) was significantly reduced in comparison with the survival of young adult AIH patients (0.78 at 18-34 years, 95% CI = 0.70-0.86) and in comparison with the survival of patients of the same age group with PBC or alcoholic cirrhosis. In conclusion, age significantly affects patient survival after liver transplantation for AIH. The increased risk of dying of infectious complications in the early postoperative period, especially above the age of 50 years, should be acknowledged in the management of AIH patients with advanced-stage liver disease who are listed for liver transplantation. It should be noted that not all risk factors relevant to patient and graft survival could be analyzed with the European Liver Transplant Registry database.

Liver Transplantation for Primary Biliary Cirrhosis: Results of Aggressive Corticosteroid Withdrawal

Introduction A subset of patients with primary biliary cirrhosis (PBC) may require long-term corticosteroid (CS) therapy following liver transplantation (OLT) due to concern over the possibility of recurrence. Our center has attempted to minimize CS use in all of our OLT recipients. In this study, we review our experience in this cohort to determine (1) patient outcome including PBC recurrence following transplantation and (2) the long-term requirement for CS use in PBC patients. Methods From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado, of which 70 patients (6.8%) with PBC received 74 allografts. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Thirteen potential predictors of CS discontinuation were considered: age, gender, body mass index (BMI), race, type of graft (cadaveric or living donor [LD]), recurrence of PBC, warm ischemia time, and immunosuppressant. Results Overall survival at 5 years was 85%. The 1-, 5-, and 10-year recurrence-free survivals were 90%, 72%, and 54%, respectively. PBC recurred in 18 patients (25.7%). Of these, none received a second transplant due to disease recurrence. At the time of last follow-up, 73% of recipients were steroid free. Independent predictors of CS discontinuation are age (>54; P = .0059) and LD graft type ( P = .0008). Conversely, cyclosporine ( P = .0007), female gender ( P = .0216), and BMI > 31 ( P = .0306) were negatively associated with CS withdraw. Importantly, steroid discontinuation did not influence PBC recurrence. Conclusions While long-term outcomes in PBC patients are favorable, disease recurrence can generally be managed medically without the need for a second transplant. Using an aggressive CS minimization approach, nearly three-quarters of the patients were CS free at the time of last follow-up. Increasing age and LD grafts were associated with successful CS withdraw. Conversely, cyclosporine use, female gender, and increasing BMI were associated with unsuccessful steroid discontinuation.

Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study

This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT). We reviewed "blindly" allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) (n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients. Granulomatous destructive cholangitis was found in five biopsies from four PBC patients (P = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis (P = 0.0002), lobular necroinflammatory activity (P < 0.0001), steatosis (P < 0.0001) and fibrosis (P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis (n = 2) or cirrhosis (n = 2). No other PBC patient had evidence of cirrhosis after OLT. Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients.

De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis

Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.

Long‐term clinical outcome of living‐donor liver transplantation for primary biliary cirrhosis

We described the recurrence of primary biliary cirrhosis (PBC) after living donor liver transplantation (LDLT) (Liver Transplantation, 7, 2001: 588). However, since the follow-up period in that study was insufficiently long (median 35.5 months), we performed a long-term study to further characterize recurrence of PBC after LDLT. From 1991 to 2006, 15 patients with end-stage PBC underwent LDLT at Tokyo Women's Medical University. Of these patients, we studied 8 PBC patients (age 29 to 51 years, all females) who survived LDLT for more than 5 years. The follow-up period for these patients ranged form 68 to 120 months. Immunosuppression was maintained with tacrolimus and prednisone. Laboratory examinations performed in every patient and donor before LDLT included routine biochemical studies, antimitochondrial antibody (AMA) by immunofluorescence (IF), anti-M2 by enzyme-linked immunosorbent assay as well as antinuclear antibody (ANA) by IF, and immunoglobulin. After LDLT, the same laboratory examinations were performed in patients every 6 months. Liver biopsy was performed when patients exhibited clinical or biochemical signs of graft dysfunction. In addition, protocol biopsy was performed every 1 to 2 years after LDLT. At the time of LDLT, all patients had end-stage cholestatic liver failure. Seven patients were positive for AMAand anti-M2 while 1 patient was negative for these markers but strongly positive for ANA. Donors were blood relatives in 6 cases, and 2 donors who were not blood relatives still exhibited multiple HLA matches with the recipients. At the end of the study in May 2006, all patients were doing well. On laboratory examination, mild abnormal liver function test results were found in 4 patients: 3 were probably due to recurrence of PBC, 1 resulted from nonalcoholic steatohepatitis. Comparison of the AMA titer between before LDLT and the most recent follow-up visit showed an increase in three patients, a decrease in two patients and no change in three patients. In contrast, the ANA titer increased in five patients. Histologically, strong evidence of recurrent PBC was found in 4 patients, and findings compatible with PBC were present in 2 additional patients. Although the number of our patients is small, our findings confirm that PBC can recur at high frequency after LDLT. However, this complication has not developed to advanced stages and has not caused appreciable symptoms in our patients, all of whom have a good quality of life.

Late-onset Sarcoidosis After Liver Transplantation for Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) and systemic sarcoidosis are granulomatous diseases of unknown etiology whose hepatic manifestations may infrequently be imitative of one another. Described herein is the first reported case in the medical literature of systemic sarcoidosis developing after liver transplantation for PBC. The presented patient, who suffered from typical clinical, laboratory, and pathologic manifestations of PBC, developed decompensated liver cirrhosis within a course of 8 years, necessitating orthotopic liver transplantation. A year and a half after transplantation, the patient developed diffuse, biopsy-proven, dermatologic and pulmonary manifestations of systemic sarcoidosis, which promptly responded to corticosteroid treatment. In retrospect, the patient's longstanding liver disease was probably caused by an unrecognizable, isolated hepatic form of sarcoidosis or an overlap between PBC and sarcoidosis. This patient illustrates the complexity that may be rarely encountered in differentiating between PBC and hepatic sarcoidosis. Discussed are the clinical, laboratory, and pathologic overlaps between hepatic sarcoidosis and PBC, and clues that may aid in the diagnosis and differentiation between the 2 disorders. Hepatologists and liver transplantation specialists should be aware of the rare possibility of hepatic sarcoidosis imitating PBC, and exacerbating systemically after liver transplantation.