Histological recurrence of autoimmune liver diseases after living-donor liver transplantation

Background:  The effects of living donor liver transplantation (LDLT) on the recurrence of autoimmune liver diseases have not been well documented. Genetic similarities may be beneficial to avoid severe rejection but may facilitate the recurrence of autoimmune diseases. Because familial occurrence of autoimmune liver diseases has been documented, there is a possibility that candidates for living-related donors may have the same disease as that of the recipients.
Method:  Between November 1994 and June 2004, 50 patients with primary biliary cirrhosis (PBC) (16-non-blood-relative donors and 34 blood-relative donors), and 28 patients with primary sclerosing cholangitis (PSC) underwent LDLT in Kyoto University Hospital.
Results:  Among 35 patients with PBC who survived more than 1 year, 10 patients (29%) showed recurrent PBC, and nine of 10 patients with recurrent PBC (90%) were associated with blood-relative donors (mean follow-up period, 30 months; range, 2–68). Two recipients had donors with some clinical or histological characteristics of PBC, and their grafts developedrecurrent PBC. Cirrhosis or graft failure was not observed in any patients with recurrent PBC. For PSC patients who survived more than 1 year after LDLT, 13 of 22 (59%) showed PSC-compatible histology and radiological findings (mean follow-up period, 31 months; range, 22–71), and five died or underwent retransplantation. Human leukocyte antigen-DR15 was positively associated with susceptibility to PSC with ulcerative colitis. One donor was revealed to have retroperitoneal fibrosis without evidence of sclerosing cholangitis.
Conclusions:  Blood-relative donors may be associated with susceptibility to recurrent autoimmune diseases. Recurrence of PSC, but not PBC, adversely affected the outcome of LDLT. Caution should be taken as blood-relative donors can be at risk of autoimmune liver diseases.     

Recurrence of primary sclerosing cholangitis after living donor liver transplantation.

BACKGROUND/AIMS: Cumulative experience in deceased donor liver transplantation for end-stage liver disease due to primary sclerosing cholangitis (PSC) suggests that liver transplantation is the treatment of choice with excellent results. Reports on the outcome of live donor liver transplantation (LDLT) for PSC, however, remain anecdotal. METHODS: The clinical course and genetic disposition of nine patients who underwent LDLT for PSC were analyzed. The median follow-up period was 3.5 years. RESULTS: Cumulated 5-year patient and graft survival rates were 90% and 71%, respectively. Recurrent PSC was diagnosed in four patients. Ratios of freedom from recurrent PSC at 1, 3, and 5 years were 100%, 73%, and 49%, respectively. The mean time to recurrence was 3.3 years. Excluding the one case with a biologically unrelated donor, recurrent PSC was diagnosed in 50% (4/8). None of the patients presented with the human leukocyte antigen-B8DR3 haplotype, which is associated with a higher susceptibility for developing PSC among the Caucasian population. Overall patient survival of LDLT for PSC seems to equal that of deceased donor liver transplantation. CONCLUSIONS: PSC might recur earlier at a higher ratio after LDLT. Further study with protocol cholangiogram and genetic considerations, including high resolution human leukocyte antigen haplotype analysis, is necessary.     

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft.     

Liver transplantation for primary sclerosing cholangitis versus primary biliary cirrhosis: A comparison of complications and outcome

Abstract Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common cholestatic disorders in adulthood requiring hepatic transplantation. Although they run similar courses, they may have different problems before and after transplantation. The aim of this study was to compare pre- and post-transplant complications and outcomes in these two similar but distinct patient groups. One hundred and seventeen adult patients underwent liver transplantation at our institution over a 6 year period, including 19 with PSC and 20 with PBC. Pre-transplant there were no significant differences in age, liver biochemistry, haematology or Child-Pugh scores between the two groups. The mean duration of disease before transplant was longer in PSC patients (11.7 vs 6.5 years; P < 0.05). The prevalence of septic cholangitis was greater in PSC (58 vs 5%; P < 0.01) as was the requirement for surgical or radiological interventional procedures, excluding cholecystectomy (53 vs 0%; P < 0.01). At transplantation, four patients with PSC had previously unrecognized cholangiocarcinoma. In the pre-transplant period these four patients had uncontrolled biliary sepsis at the time of transplant vs five of 15 PSC patients without cholangiocarcinoma. Postoperatively, PSC patients had a greater prevalence of intra-abdominal sepsis requiring surgical or radiological intervention (42 vs 5%; P < 0.05). In comparison, patients with PBC had a high prevalence of skeletal complications (30 vs 10%; P < 0.05) particularly avascular necrosis (15 vs 0%). The prevalence of chronic rejection was similar in both groups (15%). Overall survival was higher in PBC patients (85 vs 63%; P < 0.05). The prevalence of postoperative intra-abdominal sepsis requiring surgical or radiological intervention was higher in those patients with PSC who died (six of seven) compared to survivors (two of 12), (P < 0.001). Postoperative uncontrolled intra-abdominal sepsis directly contributed to more deaths in PSC patients (four of seven vs 0%). In conclusion, despite many similarities with PBC, PSC patients have higher prevalence of pre- and postoperative intra-abdominal sepsis that may contribute to poorer survival. In contrast PBC patients have excellent survival rates after a liver transplant, although bony complications are increased.     

Recurrence of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis after liver transplantation

Liver transplantation (LT) is the standard therapeutic approach for the treatment of end-stage acute and chronic autoimmune liver disease as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Results of liver transplantation in these indications are good with a patient survival after LT at 5 years of 85%. However several series have reported a possible recurrence of primary autoimmune liver disease after liver transplantation. Concerning all these three autoimmune liver diseases, recurrence of the disease on the graft may have multiple clinical, biochemical, histological and radiological expression influenced by different factors as the diagnostic methods used, the degree of immunosuppression and the genetic background of the recipient. We would like with this overview to describe the different pattern of recurrence of these autoimmune liver disease, their potential influence on the liver graft and their therapeutic management.     

Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation

Viral hepatitis and malignancy frequently recur after transplantation, but recurrence of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis is controversial. Differences in study design, number of patients, immunosuppressive treatment, length of follow-up, and criteria for recurrence account for discrepant results. Most patients with suspected recurrent disease are asymptomatic after transplantation. In patients transplanted for PBC, antimitochondrial antibodies frequently persist and do not correlate with disease recurrence; liver biopsy remains the gold standard for diagnosis. Exclusion of other disorders that can mimic PBC is paramount prior to making a diagnosis of recurrent disease. The effects of immunosuppression may modify or delay disease expression within the graft. If PBC recurs, intermediate-term patient and graft survival is excellent, but long-term studies will be necessary to address the impact of disease recurrence on the allograft. Due to lack of a diagnostic gold standard, a diagnosis of recurrent PSC after transplantation is difficult to make. An accurate diagnosis of PSC recurrence requires well-defined cholangiographic and histologic criteria. Other disorders that can produce biliary strictures after transplantation should be excluded. As with PBC, the effects of immunosuppression may modify or delay disease expression within the graft; medium-term patient and graft survival is excellent. Recurrence of autoimmune hepatitis is based on clinical, biochemical, serologic, and histologic criteria. As in patients transplanted for PBC and PSC, other conditions that can mimic autoimmune hepatitis require exclusion prior to making a diagnosis of recurrence. Most adult recipients respond to an increase in immunosuppression, whereas pediatric recipients do not respond as well. A cautious approach to withdrawal of immunosuppression is warranted in all patients transplanted for autoimmune hepatitis and the consequences of recurrent disease within the graft will require prolonged follow-up. Future studies should focus on preventive and therapeutic strategies for recurrent autoimmune diseases after transplantation.     

Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC

BACKGROUND: Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are reported to have the best outcomes after liver transplantation. Based on excellent 5-yr survival results after transplantation, it has been suggested that PSC patients may benefit from "preemptive" transplantation to reduce the risk of cholangiocarcinoma. In this study, we compared 10-yr survival of patients with PSC and PBC using a large database after adjusting for other confounding risk factors. METHODS: The United Network for Organ Sharing (UNOS) database of all patients who had liver transplantation from 1987 to 2001 was used for analysis after excluding patients with multiple organ transplantation, children, and incomplete data. RESULTS: Patients with PSC (n = 3,309) were younger than those with PBC (n = 3,254). Retransplantation rate was high in PSC (12.4%vs 8.5%; p< 0.01), and PSC was an independent predictor for retransplantation on multivariate analysis. Cox regression analysis showed that PSC patients had significantly lower graft and patient survival compared to PBC patients after adjusting for other risk factors. Lower survival in PSC became apparent 7 yr after transplantation. CONCLUSIONS: Patients with PSC had a higher retransplantation rate and lower survival when compared to PBC. Based on this analysis, we do not recommend preemptive liver transplantation for patients with PSC.     

Recurrent and de novo autoimmune liver diseases

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) each account for approximately 5% of liver transplants per year performed in the United States and Europe. Even though outcomes are excellent, with reported 5-year patient and graft survival exceeding 90% and 80%, 80% and 75%, 72% and 65% for PBC, PSC, and AIH, respectively, the issue of recurrent autoimmune liver disease after orthotopic liver transplantation is increasingly recognized as a cause of graft dysfunction, death, and need for retransplantation. This article reviews diagnostic criteria, epidemiology, risk factors, and outcomes of recurrent PBC, PSC, and AIH after liver transplantation.     

Outcome and prognostic factors of 391 Japanese patients with primary sclerosing cholangitis

Objectives: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients. Methods: Questionnaires were sent to gastroenterologists in Japan, and 391 patients with PSC were registered and enrolled in the current study. The median follow‐up was 5.3 years (range 0.1–20.8 years). The cumulative incidence for survival was analysed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox‐proportional hazards regression model for determining prognostic variables. Results: The estimated median survival of all patients was 13.1 years, with a 5‐year survival rate of 74.5%. Thirty‐eight patients (9.7%) who underwent liver transplantation (LT) had a 5‐year survival rate of 92.0%. Both univariate and multivariate analysis demonstrated that younger age [below 49 years old; odds ratio (OR)=1.76, 1.12–2.76, P=0.0136] and lower total bilirubin (below 3.0 mg/dl; OR=2.50, 1.60–3.89, P≤0.0001) were independent prognostic factors for LT‐free survival of PSC patients in Japan. Cholangiocarcinoma (CCA) was found in 14 (3.6%) patients, and only two out of 125 PSC patients exhibited a history of inflammatory bowel diseases. Conclusions: Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.     

Risk Factors for Recurrence of Primary Sclerosing Cholangitis After Living Donor Liver Transplantation: A Single Center Experience

We retrospectively reviewed our 10-year experience with living donor liver transplantation (LDLT) in 30 consecutive patients with end-stage primary sclerosing cholangitis (PSC) to determine long-term patient and graft survival and risk factors for recurrence of PSC. For strict diagnosis of recurrence, patients with hepatic artery thrombosis (n = 2), ABO blood type incompatible transplantation (n = 3), and postoperative survival shorter than 1 year (n = 5) were excluded from the study, leaving 20 patients for analysis. Recurrence was diagnosed in 11 patients 26–71 months after transplantation. Multivariate analysis showed that cytomegalovirus diseases within 3 months after transplantation and related donors were independent risk factors for recurrence. When the effects on recurrence were compared among donor-recipient relationships, there were significant differences, especially between nonrelated donors and parents. Multivariate analysis showed that age was an independent risk factor for time to graft loss. Cytomegalovirus prophylaxis and avoidance of related donors are important in reducing PSC recurrence, although this is a preliminary report with limitations due to the small number of patients. LDLT for young patients with PSC using grafts from their parents might have to be avoided where deceased donor liver transplantation is available.     

Liver transplantation for cholestatic liver disease

Opinion statement Liver transplantation is an effective form of therapy for patients with end-stage cholestatic disease that improves both survival and quality of life. Liver transplantation is very effective for the treatment of intractable pruritus but less effective for the treatment of lethargy. Survival rates are good (more than 70% at 5 years); these patients are at greater risk of developing acute and chronic rejection and are more likely to require long-term immunosuppression. Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) recur in the graft. Recurrent PSC may be difficult to differentiate from secondary sclerosing cholangitis, but it recurs in up to 60% of patients at 5 years and may reduce graft survival. PBC recurrence, noted in up to 40% of patients at 10 years, has little effect on graft survival with respect to cancers. Patients with PSC are at greater risk of both colonic cancer (which may be reduced by ursodeoxycholic acid) and cholangiocarcinoma. Diagnosis of cholangiocarcinoma before transplantation usually contraindicates transplantation. The main challenges facing liver transplantation are the need to expand the donor pool and the need to find immunosuppressive regimens with fewer long-term toxicities.     

Value of posttransplant protocol biopsies in 2 biliary autoimmune liver diseases: A step toward personalized immunosuppressive treatment

The value of protocol liver graft biopsies with good liver function was evaluated in patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC).A total of 250 protocol liver biopsy reports from 182 PSC and PBC patients were compared. Overall histopathological findings and those leading to changes in immunosuppression therapy were retrospectively analyzed.The mean time to first protocol biopsy after transplantation was 5.5 (±4.5) years for PSC patients and 9.3 (±6.6) years for PBC patients. More than 1 abnormal histopathological parameter was found in 43% and 62% of PSC and PBC patients, respectively. However, the histology was interpreted as normal by the pathologist in 78% of PSC and 60% of PBC patients. Immunosuppression therapy was reduced in 10% and increased in 6% patients due to protocol biopsy findings. Biopsies leading to increased immunosuppression therapy had more portal (P = .004), endothelial (P = .008), interphase (P = .021), and lobular (P = .000) inflammation.Mild histopathological findings were frequently found in the protocol biopsies despite the normal biochemistry. PBC patients had more histological abnormalities than those transplanted due to PSC; however, PBC patients had longer follow-up times. Immunosuppression therapy could be safely increased or decreased according to protocol biopsy findings after multidisciplinary meeting discussions.     

Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis.

Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60. 5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.     

Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center

Orthotopic liver transplantation (OLT) is an effective treatment for patients with advanced primary biliary cirrhosis (PBC). We have conducted a retrospective analysis of 400 consecutive patients transplanted for PBC between 1983 and 1999. Mean follow-up was 56 months. The proportion of patients grafted for PBC fell progressively, from 35% in 1990 (n = 80) to 21% in 1999 (n = 111); comparison of patients grafted in the 2 decades showed that the median age increased from 53 to 56 years and the median serum bilirubin at transplantation fell from 270 micromol/L to 132 micromol/L. The overall actuarial patient and graft survival at 1, 5, and 10 years is 83%, 78%, and 67% and 82%, 75%, and 61%, respectively. The net gain in 5-year survival compared with predicted survival in the absence of transplantation fell from 37% (range, 82%-90%) to 16% (range, 91%-99%). Multiple organ failure (16.1%) and sepsis (9.6%) were the major causes of early deaths (<6 months). Recurrent PBC, diagnosed on allograft histology, was found in 68 (17%) patients, at a mean time of 36 months. We were unable to identify any pretransplantation donor or recipient factor, which identified those patients at risk of recurrence, although recurrence was much earlier and more frequently seen in patients receiving tacrolimus (P =.04). PBC remains a good indication for liver transplantation, with excellent survival rates. The age at transplantation increased although patients tended to be grafted earlier. Survival rates have increased although there is a reduction in the survival benefit. Recurrence may be common, but does not seem to affect medium-term graft survival.     

Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease

Over the past decade, the outcome of liver transplantation in primary sclerosing cholangitis (PSC) patients with end-stage liver disease has improved significantly with many centres reporting 1-year patient and graft survival of 90-97% and 85-88%, respectively. Based on these results, liver transplantation has emerged as the treatment of choice for PSC patients. Specific complications related to PSC remain problematical. Inflammatory bowel disease (IBD) occurs in 70% of patients, and there is a distinctly increased risk of colorectal neoplasia both pre- and post-transplantation. Furthermore, symptoms related to IBD post-transplantation can become severe and lead to the need for proctocolectomy. Cholangiocarcinoma remains a major risk facing the PSC patient and develops in 15-30% of patients. Markers to detect the early neoplastic changes of cholangiocarcinoma are not available. To date, outcome following liver transplantation in PSC patients who have associated cholangiocarcinoma has been dismal. However, those patients who are found to have an incidental cholangiocarcinoma have an acceptable low incidence of recurrence of disease. To assess optimal timing of liver transplantation, natural history risk scores have been developed and utilized. Utilizing such risk scores, estimated survival for the individual PSC patient can be obtained. Finally, there is an increased incidence of both acute and chronic rejection, hepatic artery thrombosis and biliary stricturing in PSC patients undergoing liver transplantation. A late rise in serum alkaline phosphatase level is almost always indicative of biliary stricturing and recurrence of disease. Approximately 20% of patients followed for 5 years or more will have recurrence of PSC documented both on cholangiography and histology.     

Recurrence of primary sclerosing cholangitis following liver transplantation

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.     

Liver transplantation and autoimmunity.

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent good indications for orthotopic liver transplantation (OLT). While there is effective treatment for AIH (steroids with or without azathioprine) and PBC (ursodeoxycholic acid) no such treatment is currently established for PSC. The need of transplantation can be delayed for AIH and PBC with appropriate therapies, while treatment options for PSC are still controversially discussed. Although the time point for liver transplantation can be roughly estimated for AIH by failure of immunosuppressive therapy and for PBC by prognostic models, the prediction of survival in patients with PSC is more difficult, and further complicated by the risk of developing cholangiocellular carcinoma. Long term (5-year) outcome after liver transplantation approaches 80 to 90% for autoimmune liver diseases unless cholangiocellular carcinoma complicates PSC at the time of OLT. The risk of disease recurrence has been recognised for each of these entities although its clinical relevance is controversial and not exactly determined today. As survival after liver transplantation is steadily increasing, recurrent autoimmune liver disease may become a clinical problem in the future. Recently de novo autoimmune hepatitis after liver transplantation has been reported from several transplant centres, although its importance still needs to be established.     

Liver transplantation in autoimmune liver disease--selection of patients

Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune liver diseases, which are good indications for orthotopic liver transplantation (OLT). While there is effective treatment for AIH (steroids with or without azathioprine) and PBC (Ursodesoxycholic acid) no such treatment is currently established for PSC. The need for transplantation can be delayed for AIH and PBC with appropriate therapies, while treatment options for PSC are still controversially discussed. Although the time point for liver transplantation can be roughly estimated for AIH by failure of immunosuppressive therapy and for PBC by prognostic models, the prediction of survival in patients with PSC is more difficult, and further complicated through the risk of developing cholangiocellular carcinoma (CCC). Long-term (5-year) outcome after liver transplantation approaches 80-90% for autoimmune liver diseases unless CC complicates PSC at the time of OLT. The risk of disease recurrence has been recognized for each of these entities although its clinical relevance is controversial. This gets more important as long-term survival can be achieved for most of these patients today. In this review the natural course of autoimmune liver disease will be discussed and prognostic models will be presented, which are helpful for finding the optimal time point for liver transplantation.     

Liver transplantation in primary biliary cirrhosis

The proportion of patients who undergo liver transplantation for primary biliary cirrhosis (PBC) is steadily declining. This decline is partly from the increasing number of patients undergoing transplantation for other indications, but also perhaps because of the effect of ursodeoxycholic acid (UDCA) on the natural history of this condition. Nevertheless, patients who have PBC still constitute approximately 11% of all patients undergoing transplantation for cirrhosis. The prognosis after transplantation is excellent, with an approximately 80% 5-year survival reported by most large centres. Liver transplantation also significantly improves quality of life in survivors. The disease may recur after surgery in up to one third of patients, but recurrence has not been shown to have a significant effect on patients' survival in the medium term.     

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

Aim:  This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT).
Methods:  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.
Results:  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.
Conclusions:  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.