External validation of the IAIHG autoimmune hepatitis response criteria in a multicentric real-world cohort.

Background & Aims: The goal of treatment in autoimmune hepatitis (AIH) is induction of remission to prevent the development of liver fibrosis, cirrhosis, and its related complications. Various definitions of treatment response and remission have been used. The International Autoimmune Hepatitis Group (IAIHG) recently defined consensus criteria for treatment response. We aimed to validate the IAIHG response criteria in our cohort and establish correlations with survival endpoints. Methods: We performed a retrospective, multicentric cohort study in one tertiary and seven secondary care centres in Belgium. Eligible patients were at least 18 years of age at data collection and were diagnosed with AIH by a simplified IAIHG score of ≥6. Complete biochemical response (CBR) was defined according to the IAIHG consensus criteria as normalisation of transaminases and serum IgG within the first 6 months of treatment. The primary endpoint was liver-related survival - defined as freedom from liver-related death or liver transplantation. Secondary endpoints were overall mortality and transplant-free survival. Outcomes were compared between patients attaining CBR and those with insufficient response. Results: Biochemical response status could be determined in 200 patients with AIH: CBR was achieved in 128 (64.0%) individuals. Patients not achieving CBR more frequently presented with cirrhosis on initial histology (22.2% vs. 10.9%, p = 0.036). Liver-related mortality or liver transplantation as a primary outcome occurred in 26 patients (13.0%). Patients achieving CBR exhibited superior liver-related (hazard ratio 0.118; 95% CI 0.052-0.267; p <0.0001) and overall (hazard ratio 0.253; 95% CI 0.111-0.572; p = 0.0003) survival. Conclusions: We externally validated the IAIHG consensus criteria for CBR and confirmed their correlation with survival endpoints in a multicentric, real-world cohort. Patients with AIH achieving CBR as an intermediate endpoint have significantly superior liver-related and overall survival. Impacts and Implications: Corticosteroids remain the cornerstone of treatment to induce remission of disease activity in autoimmune hepatitis (AIH), and the majority of patients require long-term corticosteroid treatment to achieve sustained remission. Definitions of response to treatment have varied over the years, and consistently used intermediate endpoints are needed to facilitate advancements in non-corticosteroid treatment for autoimmune hepatitis. The International Autoimmune Hepatitis Group (IAIHG) defined consensus criteria on endpoints in the treatment of AIH, for which further external validation is needed. Here, we demonstrate the usefulness of the IAIHG consensus criteria and corroborate their correlation to primary endpoints, such as liver-related survival and native liver survival in a multicentric, real-world setting. The design of future studies can rely on the IAIHG consensus criteria as intermediate endpoints.

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.

A multicentre interventional study to assess blood-borne viral infections in Belgian prisons.

BACKGROUND: Prevalence data on viral hepatitis B (HBV), hepatitis C (HCV), and HIV infection in prison are often scarce or outdated. There is currently no systematic screening for these blood-borne viral infections (BBV) in Belgian prisons. There is an urgency to assess the prevalence of these BBV to inform policymakers and public healthcare. METHODS: This was a multicentre, interventional study to assess the prevalence of BBV using opt-in screening in prisons across Belgium, April 2019 - March 2020. Prisoners were tested using a finger prick and BBV risk factors were assessed using a questionnaire. A generalized linear mixed model was used to investigate the association between the various risk factors and HCV. RESULTS: In total, 886 prisoners from 11 Belgian prisons were screened. Study uptake ranged from 16.9 to 35.4% in long-term facilities. The prevalence of HCV antibodies (Ab), hepatitis B surface antigen (Ag) and HIV Ab/Ag was 5.0% (44/886), 0.8% (7/886), and 0.2% (2/886). The adjusted odds for HCV Ab were highest in prisoners who ever injected (p < 0.001; AOR 24.6 CI 95% (5.5-215.2). The prevalence of detectable HCV RNA in the total cohort was 2.1% (19/886). Thirteen (68.4%) prisoners were redirected for follow-up of their HCV infection. CONCLUSIONS: Opt-in testing for viral hepatitis B, C and HIV was relatively well-accepted in prisons. Compared with the general population, prisoners have a higher prevalence of infection with BBV, especially for HCV. Systematic screening for these BBV should be recommended in all prisons, preferably using opt-out to optimize screening uptake. TRIAL REGISTRATION: Retrospectively registered at clinical trials NCT04366492 April 29, 2020.

Efficacy and safety of radiofrequency ablation of Barrett's esophagus in the absence of reimbursement: a multicenter prospective Belgian registry.

BACKGROUND: Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS: Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS: 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS: Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

Characteristics of patients with hepatitis B virus and hepatitis C virus dual infection in a Western European country: Comparison with monoinfected patients.

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is continuously evolving. Updated data on dual HBV and HCV infection are still needed. AIMS: To assess the main characteristics of patients with HBV and HCV dual infection, to compare these with those of patients infected with either HBV or HCV and, among patients with dual infection, to assess fibrosis according to HCV replication. METHODS: Data of 23 patients with dual infection were compared to data from 92 age and sex-matched HBV or HCV monoinfected patients. RESULTS: Patients with dual infection were more often immigrants from Africa or Asia than HCV or HBV patients (52% vs. 20% and 22%, respectively, P=0.01). Intravenous drug use was the route of transmission in 22% of patients with dual infection, which was less frequent than in HCV patients (41%) but more frequent than in HBV patients (0%). Extensive fibrosis or cirrhosis was as frequent among dual-infected patients as among those with HCV or chronic hepatitis B infection (19% vs. 29% vs. 14%, respectively, P=0.4), even when fibrosis stage was reported considering the duration of infection. In dual-infected patients, the prevalence of extensive fibrosis or cirrhosis was similar in patients with and without detectable HCV RNA (18% vs. 20%). CONCLUSIONS: Patients with HBV and HCV dual infection were more often immigrants from Africa or Asia and had similar fibrosis stages than HCV or HBV monoinfected patients. In patients with dual infection, extensive fibrosis or cirrhosis was not associated with HCV replication.

Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or without ribavirin and JNJ-56914845 in HCV genotype 1 infection.

BACKGROUND: A Phase 2a, open-label study (NCT01724086) was conducted to assess the efficacy and safety of a once-daily, 2-direct-acting-antiviral-agent (2-DAA) combination of simeprevir + TMC647055/ritonavir ± ribavirin and of the 3-DAA combination of simeprevir + TMC647055/ritonavir + JNJ-56914845 in chronic hepatitis C virus genotype (GT)1-infected treatment-naïve and prior-relapse patients. METHODS: The study comprised four 12-week treatment panels: Panel 1 (n = 10; GT1a) and Panel 2-Arm 1 (n = 12; GT1b): simeprevir 75 mg once daily + TMC647055 450 mg once daily/ritonavir 30 mg once daily + ribavirin 1000-1200 mg/day; Panel 2-Arm 2 (n = 9; GT1b): simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg without ribavirin; Panel 3: simeprevir 75 mg + TMC647055 600 mg/ritonavir 50 mg with (Arm 1: GT1a; n = 7) or without (Arm 2: GT1b; n = 8) ribavirin; Panel 4: simeprevir 75 mg + TMC647055 450 mg/ritonavir 30 mg + JNJ-56914845 30 mg once daily (Arm 1: n = 22; GT1a/GT1b) or 60 mg once daily (Arm 2: n = 22; GT1a/GT1b). Primary endpoint was sustained virologic response 12 weeks after end of treatment (12 weeks of combination treatment; SVR12). RESULTS: In Panel 1 and Panel 2-Arm 1, 5/10 and 6/12 (50%) GT1a/GT1b + ribavirin patients achieved SVR12, versus 3/9 (33%) GT1b without ribavirin patients in Panel 2-Arm 2. In Panel 3-Arm 1 and Panel 3-Arm 2, 6/7 (86%) GT1a + ribavirin and 4/8 (50%) GT1b without ribavirin patients, respectively, achieved SVR12. In Panel 4, 10/14 (71%) and 14/15 (93%) GT1a patients in Arms 1 and 2 achieved SVR12 compared with 8/8 and 7/7 (100%) GT1b patients in each arm, respectively. No deaths, serious adverse events (AEs), Grade 4 AEs or AEs leading to treatment discontinuation occurred. CONCLUSIONS: The 2- and 3-DAA combinations were well tolerated. High SVR rates of 93% and 100% in GT1a- and GT1b-infected patients, respectively, were achieved in this study by combining simeprevir with JNJ-56914845 60 mg and TMC647055/ritonavir. TRIAL REGISTRATION: NCT01724086 (date of registration: September 26, 2012).

Sofosbuvir in Combination with Simeprevir +/- Ribavirin in Genotype 4 Hepatitis C Patients with Advanced Fibrosis or Cirrhosis: A Real-World Experience from Belgium.

INTRODUCTION: Hepatitis C virus (HCV) is a major global health issue and successful treatment has been associated with a reduction of risk of all-cause mortality. Advancements have been made in HCV treatment through the use of interferon-free regimens. Most trials have been conducted in HCV genotype (GT) 1 and data for interferon-free regimens in GT4 patients are limited. The aim of this study was to evaluate the safety and efficacy of sofosbuvir plus simeprevir in a real-world cohort of HCV GT4 patients with advanced fibrosis. PATIENTS AND METHODS: Eighty-seven GT4 treatment-naïve or -Interferon (IFN) ribavirin (RBV) experienced patients treated with sofosbuvir and simeprevir +/- ribavirin (RBV) were enrolled in this cohort study (41% severe fibrosis, 59% cirrhosis). RESULTS: Patients were 51.7% male, 78.2% IFN/RBV treatment-experienced, and 37.9% received RBV treatment. The overall sustained virologic response at least 12 weeks after treatment (SVR12) rate was 87.4% while patients treated with and without RBV had rates of 87.9% and 87% (p = 0.593), respectively, and patients with advanced fibrosis (F3) and patients with cirrhosis had SVR12 rates of 94.4% and 82.4% (p = 0.087), respectively. SVR12 rates in treatment-naïve patients and in IFN/RBV -experienced patients were 78.9% and 89.7% (p = 0.191), respectively. Treatment failure occurred most commonly in patients with cirrhosis and severe disease. The treatment was well tolerated and no patient died or discontinued treatment due to adverse events. CONCLUSIONS: Sofosbuvir in combination with simeprevir +/- ribavirin in GT 4 HCV patients with advanced fibrosis achieved high SVR12 rates and was well tolerated. RBV did not appear to increase the rate of SVR12.

Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form.

As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis.

Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study.

BACKGROUND & AIMS: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS: Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS: 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS: Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.

Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids.

BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a life-threatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18-75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%-55.9%) and 52.1% of controls died (95% CI, 39.4%-63.4%) (P = .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8-78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%-43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment. ClinicalTrials.gov number: NCT01801332.

Mitochondrial hepatopathy in adults: a case series and review of the literature.

AIM: Mitochondrial diseases affect about 1/5000-1/10000 in the population. Twenty percent of patients with mitochondrial disease show liver involvement. In contrast to current belief among most internists, these diseases do not only present in childhood. METHODS: We present four cases of adults (three with Alpers-Huttenlocher syndrome and one with mitochondrial neurogastrointestinal encephalomyopathy), diagnosed between 2005 and 2010, in our university referral center. RESULT: We focus on the broad clinical spectrum of liver involvement in mitochondrial diseases and their diagnosis. Biochemical investigations are often found to be inconclusive, and genetic confirmation cannot always be obtained, leaving many patients without a final diagnosis. Evidence-based causal therapy is unavailable for most mitochondrial diseases and liver transplantation for this indication remains a controversial issue. CONCLUSION: For clinicians, it is important to consider the possibility of an underlying mitochondrial disorder when there is systemic involvement (more than one organ affected), a suggestive family history, or an elevated level of lactic acid in the blood or cerebrospinal fluid.

Hepatitis B virus and hepatitis C virus infections in Belgium: similarities and differences in epidemics and initial management.

INTRODUCTION: Nationwide studies comparing patients with hepatitis B and C virus (HBV and HCV) infections are mandatory for assessing changes in epidemiology. AIM: The aim of this study was to compare epidemiological data and initial management of newly diagnosed patients with persistent HBV (HBsAg positive) or HCV (detectable HCV RNA) infection in Belgium. PATIENTS AND METHODS: Data were extracted from two Belgian observational databases. RESULTS: A total of 655 patients (387 HBV and 268 HCV) were included. Compared with HCV patients, HBV patients were younger, more frequently men, more often of Asian or African origin (43 vs. 10%, P<0.0001), and less frequently contaminated by transfusion or intravenous drug use (9 and 6% vs. 34 and 44%, P<0.0001). Viral replication was assessed in 89% of HBV patients. Compared with HCV patients, HBV patients more frequently had normal alanine aminotransferase (ALT) levels (65 vs. 29%, P<0.0001), less frequently underwent liver biopsy (29 vs. 67%, P<0.0001), and were less often considered for antiviral therapy (25 vs. 54%, P<0.0001). When taking only HBV patients with detectable viral replication into consideration, results remained unchanged. During the multivariate analysis, ALT was a major factor for performing liver biopsy or considering antiviral therapy in both groups. CONCLUSION: HBV and HCV screening policies should be targeted toward immigrants and intravenous drug users, respectively. Guidelines recommending systematic search for viral replication should be reinforced in HBV patients. HBV patients less frequently underwent liver biopsy and were less often considered for antiviral therapy compared with HCV patients. Despite the lack of sensitivity and specificity, ALT remains a pivotal decision-making tool for liver biopsy and antiviral therapy in both infections.

HBV infection in Belgium: results of the BASL observatory of 1,456 HBsAg carriers.

INTRODUCTION: Nationwide studies are mandatory to assess changes in the epidemiology of HBV infection in Europe. AIM: To describe epidemiological characteristics of HBsAg-positive patients, especially inactive carriers, and to evaluate how practitioners manage HBV patients in real life. METHODS: Belgian physicians were asked to report all chronically infected HBV patients during a one-year period. RESULTS: Among 1,456 patients included, 1,035 (71%) were classified into one of four phases of chronic infection: immune tolerance (n = 10), HBeAg-positive hepatitis (n = 248), HBeAg-negative hepatitis (n = 420) and inactive carrier state (n = 357 HBeAg-negative patients with ALT

IL28B polymorphism and the control of hepatitis C virus infection: ready for clinical use?

Polymorphisms in the region of the interleukin-28B (IL28B) gene have recently been associated with spontaneous and treatment induced clearance of hepatitis C virus infection. The specific mechanisms of how IL28B polymorphisms affect HCV suppression remain unknown. It is a matter of ongoing debate how to incorporate the IL28B data into the current treatment algorithms with pegylated interferon-alpha and ribavirin. The eventual role of the IL28B genotype in new therapeutic regimes with direct antiviral agents needs to be explored in the ongoing and future clinical studies with these agents.

Progressive multifocal leukoencephalopathy in liver transplant recipients: a case report and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of the JC polyomavirus in immunocompromised patients. We report a case of PML in a liver transplant recipient and review the other published cases. The clinical course of PML is characterised by a rapid progressive neurological decline coinciding with the presence of white matter lesions on magnetic resonance images. There is no direct antiviral therapy available against the JC polyomavirus. Restoration of the immune response achieved by tapering or terminating the immunosuppressive regimen is the mainstay of treatment at present in transplanted patients. The prognosis remains, however, extremely poor regardless of treatment.

Large spectrum of liver vascular lesions including high prevalence of focal nodular hyperplasia in patients with hereditary haemorrhagic telangiectasia: the Belgian Registry based on 30 patients.

OBJECTIVES: We report the Belgian Registry of 30 patients (19 women and 11 men) with hereditary haemorrhagic telangiectasia (HHT) and liver involvement. RESULTS: Twenty-three patients (77%) were asymptomatic. Within the seven symptomatic patients (23%), four suffered from high output cardiac failure, two died before liver transplantation and one was transplanted. Three patients developed symptomatic biliary disease, two were transplanted and one was listed. Intrahepatic shunts and a large hepatic artery (6-14 mm, mean: 9.3 mm) were found in all patients and are characteristic of liver involvement. We observed a high prevalence (47%) of asymptomatic hepatic tumours with radiological and histological characteristics of focal nodular hyperplasia (FNH) for the majority of these tumours. The histological examination of the three explanted livers revealed the coexistence of a large spectrum of hepatic vascular lesions including intrahepatic shunts, FNH, nodular regenerative hyperplasia, sinusoidal dilatation and ischaemic cholangiopathy. All these lesions should be diagnosed early to avoid invasive procedures even if a liver biopsy was performed in six of our patients without complications. The liver biopsy led to the diagnosis of HHT in one patient and to FNH in another one. CONCLUSION: Liver involvement in HHT is characterized by a high prevalence of FNH and a large spectrum of vascular lesions such as intrahepatic shunts, nodular regenerative hyperplasia, sinusoidal dilatation and ischaemic cholangiopathy that may coexist simultaneously in the same patient.