Prognostic Scores for Ursodeoxycholic Acid-Treated Patients Predict Graft Loss and Mortality in Recurrent Primary Biliary Cholangitis after Liver Transplantation.

BACKGROUND/AIM: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of scores for PBC to predict the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centres across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2 - 62.6], and 298 patients (90%) were females. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3 - 12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (HR, 3.97, 95%CI 1.36-11.55, P=0.01), use of prednisone (HR 3.18, 95%CI 1.04-9.73, P=0.04), ALP xULN (HR 1.59, 95%CI 1.26-2.01, P<0.001), Paris-2 criteria (HR 4.14, 95%CI 1.57-10.92, P=0.004), GLOBE score (HR 2.82, 95%CI 1.71-4.66, P<0.001), and the UK-PBC score (HR 1.06, 95%CI 1.03-1.09, P<0.001) were associated with graft survival in the multivariate analysis. Similar results were found in the overall survival analysis. CONCLUSION: Patients with rPBC and disease activity as indicated by standard PBC risk scores have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who have liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid according to conventional prognostic scores have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results emphasized supporting efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.

Questionnaire PLD-complaint-specific assessment identifies need for therapy in polycystic liver disease: A multi-centric prospective study.

BACKGROUND AND AIMS: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation. METHODS: A five-year prospective multi-centric observational study in 21 hospitals in Belgium gathered a study population of 198 symptomatic PLD-patients of whom the disease-specific symptom questionnaire PLD-complaint-specific assessment (POLCA) scores were calculated. The thresholds of the POLCA score for the need for volume reduction therapy were analyzed. RESULTS: The study group consisted of mostly (82.8%) women with baseline mean age of 54.4 years ±11.2, median liver volume expressed as height-adjusted total liver volume(htLV) of 1994 mL (interquartile range [IQR] 1275; 3150) and median growth of the liver of +74 mL/year (IQR +3; +230). Volume reduction therapy was needed in 71 patients (35.9%). A POLCA severity score (SPI) ≥ 14 predicted the need for therapy both in the derivation (n = 63) and the validation cohort (n = 126). The thresholds to start somatostatin analogues (n = 55) or to consider liver transplantation (n = 18) were SPI scores of ≥14 and ≥ 18 and the corresponding mean htLVs were 2902 mL (IQR 1908; 3964) and 3607 mL (IQR 2901; 4337), respectively. Somatostatin analogues treatment resulted in a decrease in the SPI score -6.0 versus + 4.5 in patients without somatostatin analogues (p < 0.01). Changes in the SPI score were significantly different between the liver transplantation group and no liver transplantation group, +4.3 ± 7.1 versus -1.6 ± 4.9, respectively, (p < 0.01). CONCLUSION: A polycystic liver disease-specific questionnaire can be used as a guide on when to start a volume reduction therapy and to assess the effect of treatment.

Elimination of hepatitis C virus infection in patients with haemophilia in Belgium: A single-centre experience.

INTRODUCTION: Patients with haemophilia are one of the subgroups with a high prevalence of hepatitis C virus (HCV) infection. They are a potential target group to eliminate HCV infection thanks to the availability of direct-acting antiviral (DAA) therapy. AIM: To investigate the results of DAA therapy in a cohort of patients with bleeding disorders. METHODS: This retrospective study was conducted between July 2018 and April 2019. All patients born before 1990 with haemophilia, von Willebrand factor Disease, factor V deficiency, factor VII deficiency or afibrinogenemia were included in this study. RESULTS: Of 299 patients, 297 (99.3%) were tested for HCV antibody presence and 211 (71.0%) were positive. Of these, 205 (97.1%) were tested for HCV RNA and 153 (72.1%) were chronically infected. In total, 127 (83.0%) received antiviral therapy, and 110 (71.8%) patients were cured by antiviral treatment. The presence of cirrhosis was significantly higher in patients without a cure for HCV infection when compared to patients who achieved sustained virologic response by treatment or never infected (32.6% vs. 12.8% vs. 0%; P < .001). At the end of follow-up in 2019, only 14 (9.1%) patients had a remaining HCV infection. Ten (71.4%) were lost to follow-up, one (7.1%) patient refused, two (14.2%) had comorbidities and one (7.1%) will start treatment soon. CONCLUSION: In this cohort, the elimination targets for HCV infection in 2030 as proposed by the World Health Organization were already reached. Nevertheless, in order to cure every patient, monitoring tools are necessary.

Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group). METHODS: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years). RESULTS: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 µmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02). CONCLUSIONS: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects.