Recurrent Primary Biliary Cirrhosis Research Articles

Relapse of autoimmune diseases after liver transplantation

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p<0.0001).Conclusions. The recurrence of autoimmune diseases leads to a decrease in graft survival. The effect of immunosuppression components on the risk of recurrence of autoimmune diseases in the graft has not been established.

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.

Risk factors for recurrent autoimmune liver diseases after liver transplantation: A meta-analysis.

Background:Autoimmune liver disease (ALD) is a chronic liver disease caused by immune dysfunction in the body. However, no causative or curative medical treatment with proven efficacy exists to cure ALDs, and liver transplantation (LT) remains the only effective treatment available. However, the problem of recurrence of ALDs (rALDs) still remains after LT, which seriously affects the survival rate of the patients. Therefore, clinicians need to be aware of the risk factors affecting rALDs after LT. Therefore, this meta-analysis aims to define the risk factors for rALDs, which include the recurrence of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis.Methods:A systematic search in Pubmed, Embase, Cochrane library and Web of Science databases was performed from 1980 to 2019. The inclusion criteria were risk factors for developing rALDs after LT. However, case series, case reports, reviews, meta-analysis and studies only including human immunodeficiency virus cases, children, and pregnant patients were excluded.Results:The electronic database search yielded 1728 results. Sixty-three retrospective cohort studies met the inclusion criteria and 13 were included in the meta-analysis. The final cohort included 5077 patients, and among them, 21.96% developed rALDs. Colectomy before LT, HR 0.59 (95% confidence interval [CI]: 0.37-0.96), cholangiocarcinoma, HR 3.42 (95% CI: 1.88–6.21), multiple episodes of acute cellular rejection, HR 2.07 (95% CI: 1.27–3.37), model for end-stage liver disease score, HR 1.05 (95% CI: 1.02–1.08), use of mycophenolate mofetil, HR 1.46 (95% CI: 1.00–2.12) and the use of cyclosporin A, HR 0.69 (95% CI: 0.49–0.97) were associated with the risk of rprimary sclerosing cholangitis. In addition, the use of tacrolimus, HR 1.73 (95% CI: 1.00–2.99) and cyclosporin A, HR 0.59 (95% CI: 0.39–0.88) were associated with the risk of rALD.Conclusions:Multiple risk factors for rALDs were identified, such as colectomy before LT, cholangiocacinoma, multiple episodes of acute cellular rejection, model for end-stage liver disease score, and especially the use of mycophenolate mofetil, cyclosporin A and tacrolimus.

Autoimmune Liver Disease Post-Liver Transplantation: A Summary and Proposed Areas for Future Research.

Autoimmune liver diseases (AILD) are rare diseases with a reported prevalence of less than 50 per 100 000 population. As the research landscape and our understanding of AILDs and liver transplantation evolves, there remain areas of unmet needs. One of these areas of unmet needs is prevention of disease recurrence after liver transplantation. Disease recurrence is not an insignificant event because allograft loss with the need for retransplantation can occur. Patients transplanted for AILD are more likely to experience acute rejection compared to those transplanted for non-AILD, and the reason(s) behind this observation is unclear. Tasks for the future include a better understanding of the pathogenesis of AILD, definition of the precise pathogenetic mechanisms of recurrent AILD, and development of strategies that can identify recipients at risk for disease recurrence. Importantly, the role of crosstalk between alloimmune responses and autoimmune responses in AILD is an important area that needs further study.This article reviews the relevant literature of de novo autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary sclerosing cholangitis, and recurrent primary biliary cirrhosis in terms of the clinical entity, the scientific advancements, and future scientific goals to enhance our understanding of these diseases.

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.

The clinical analysis of orthotopic liver transplantation for primary biliary cirrhosis

To analyze the clinical outcome and complications of orthotopic liver transplantation (OLT) for patients with primary biliary cirrhosis(PBC). Clinical data of 25 patients with PBC who underwent OLT were analyzed retrospectively. The postoperative cumulative survival rate of the patients was calculated. The postoperative recurrence of PBC, de novo diseases and other complications were analyzed. A total of 25 patients were recruited including 22 females and 3 males. The average age was 49.1 years (range from 40 to 64 years). The score of model for end-stage liver disease (MELD) was 21.80±5.49, and the Mayo score 8.01±1.38. Four patients died after liver transplantation. The 1-year, 2-year and 7-year patient cumulative survival rates were 92.0%, 87.8% and 75.3%, respectively. Eight cases (32.0%) developed recurrent PBC based on histological evidence. The median time to recurrence was 17.5 months. One of the eight patients with recurrent PBC was diagnosed with de novo auto-immune hepatitis (AIH) simultaneously, who eventually died. Acute rejection and de novo hepatitis B virus (HBV) infection developed in thirteen (52.0%) patients and five (20.0%) patients, respectively. Two cases (8.0%) of de novo AIH were diagnosed, one of which was fatal. OLT is an effective procedure for end-stage PBC. Much attention needs to be paid to the post-transplantation complications, including recurrence of primary disease, combined de novo HBV infection, de novo AIH, etc.

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.

In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins.

In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation.

P1148 : Long-term administration of ursodeoxycholic acid prevents recurrence of primary biliary cirrhosis after liver transplantation

P1148 : Long-term administration of ursodeoxycholic acid prevents recurrence of primary biliary cirrhosis after liver transplantation

Innate immunity drives xenobiotic-induced murine autoimmune cholangitis

Although primary biliary cirrhosis (PBC) is considered a model autoimmune disease, it has not responded therapeutically to traditional immunosuppressive agents. In addition, PBC may recur following liver transplantation, despite the absence of major histocompatibility complex (MHC) matching, in sharp contrast to the well-known paradigm of MHC restriction. We have suggested previously that invariant natural killer T (iNK T) cells are critical to the initiation of PBC. In this study we have taken advantage of our ability to induce autoimmune cholangitis with 2-octynoic acid, a common component of cosmetics, conjugated to bovine serum albumin (2-OA-BSA), and studied the natural history of pathology in mice genetically deleted for CD4 or CD8 following immunization with 2-OA-BSA in the presence or absence of α-galactosylceramide (α-GalCer). In particular, we address whether autoimmune cholangitis can be induced in the absence of traditional CD4 and CD8 responses. We report herein that CD4 and CD8 knock-out mice immunized with 2-OA-BSA/PBS or 2-OA-BSA/α-GalCer develop anti-mitochondrial antibodies (AMAs), portal infiltrates and fibrosis. Indeed, our data suggest that the innate immunity is critical for immunopathology and that the pathology is exacerbated in the presence of α-GalCer. In conclusion, these data provide not only an explanation for the recurrence of PBC following liver transplantation in the absence of MHC compatibility, but also suggest that effective therapies for PBC must include blocking of both innate and adaptive pathways.

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.

E. coliInduced Experimental Model of Primary Biliary Cirrhosis: At Last

Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC.

Primary biliary cirrhosis in the era of liver transplantation.

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.

Switching From Tacrolimus to Cyclosporine A to Prevent Primary Biliary Cirrhosis Recurrence After Living-Donor Liver Transplantation

Recurrence of primary biliary cirrhosis (PBC) after liver transplantation has been shown to negatively affect graft and patient survival. Recently, protective effects of cyclosporine A against PBC recurrence after liver transplantation have been reported. Participants were 4 patients who underwent living-donor liver transplantation (LDLT) for end-stage liver disease due to PBC. Tacrolimus was used for initial immunosuppression, and this was switched to cyclosporine A at least 3 months after liver transplantation. Targeted trough level of cyclosporine A was 20 times that of tacrolimus. We assessed liver and renal function, as well as antimitochondrial M2 antibody for recipients prior to LDLT, as well as before and after switching immunosuppressive agents. Patients were 1 man and 3 women, and they were ages 45 to 47 years at LDLT. Timing of switching from tacrolimus to cyclosporine A was 13, 3, 7, and 4 months respectively after liver transplantation, and all 4 patients have been on cyclosporine A without adverse effects at 20 to 46 months after transplantation. In 2 of 4 patients who had high titers of antimitochondrial M2 antibody before transplantation, antibody titer did not elevate after LDLT. In the other 2 patients without elevation of antimitochondrial M2 antibody, the titer did not turn positive. Switching from tacrolimus to cyclosporine A was possible without medical problems, and all patients exhibit no recurrence of PBC. Cyclosporine A may be useful for prevention of PBC recurrence after LDLT.

Calcineurin Inhibitors and the IL12A Locus Influence Risk of Recurrent Primary Biliary Cirrhosis After Liver Transplantation

Calcineurin Inhibitors and the IL12A Locus Influence Risk of Recurrent Primary Biliary Cirrhosis After Liver Transplantation

Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro.

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

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.

Primary biliary cirrhosis and liver transplantation.

Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5- and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival.

The immunoreactive patient: Rejection and autoimmune disease

1. Despite highly potent immunosuppression regimens, there is a small cohort of patients at risk of graft failure due to rejection. 2. Steroid-resistant rejection is managed by the escalation of immunosuppression, but only one-third of patients with chronic rejection respond to this approach. 3. Interferon therapy for recurrent hepatitis C may induce an immunoreactive state and increase rejection rates. 4. Cyclosporine reduces the risk of recurrence of primary biliary cirrhosis but does not alter survival rates. 5. Patterns of primary sclerosing cholangitis recurrence are not affected by immunosuppression. 6. Autoimmune hepatitis recurrence and de novo autoimmune hepatitis are corticosteroid-responsive in most cases.