[Polycystic liver disease]. / Polykystoses hépatiques.

Polycystic liver disease (PLD) includes three entities in adults : biliary hamartomas which develop as a result of ductal plate malformation, autosomal dominant polycystic liver disease (ADPLD) and autosomal dominant polycystic kidney disease (ADPKD) which occur in the setting of genetic disorders. Hamartomas are asymptomatic and benign. PLD are marked by a steady growth of cysts over time, clinically silent in the majority of cases. Symptomatic forms mainly affect women due to the influence of estrogens on the growth of cysts therefore estrogen treatments are contraindicated in this setting. Diagnosis is based on imaging. Complications are rare but must be identified early in order to offer appropriate care in an expert center.

Les polykystoses hépatiques (PKH) de l'adulte regroupent les hamartomes biliaires, conséquence d'une malformation congénitale de la plaque ductale, la polykystose hépatorénale autosomique dominante (PKHRAD) et la polykystose hépatique isolée (PKHI), de cause génétique. Les hamartomes sont asymptomatiques et bénins. Les PKH sont marquées par une croissance régulière des kystes au fil du temps, silencieuse dans la majorité des cas. Les formes symptomatiques concernent majoritairement les femmes, la croissance des kystes étant influencée par les œstrogènes. De ce fait, les traitements œstrogéniques doivent être proscrits. Le diagnostic repose sur l'imagerie. Les complications sont rares mais doivent être identifiées précocement afin de proposer une prise en charge adaptée en centre expert.

Hepatic Alveolar Echinococcosis.

Hepatic alveolar echinococcosis (HAE) is a rare but severe zoonosis caused by the pseudotumoral intrahepatic development of the larval stage of the tapeworm Echinococcus multilocularis. HAE is present only in the Northern Hemisphere, predominantly in China. Currently, there is a significant resurgence of cases in historically endemic areas associated with emergence of HAE in countries not previously concerned. Today, in European countries, HAE is often discovered by chance; however, clinicians should be made aware of opportunistic infections that progressively emerged recently as a result of therapeutic or pathological immunosuppression. Ultrasonography is the key first-line diagnostic procedure, with specific serology providing confirmation in 95% of the cases. Albendazole, only parasitostatic, is the mainstay for treatment. Surgical resection, if feasible, is the gold standard for treatment, and more patients are currently eligible for this option because of an earlier diagnosis. The prognosis has considerably improved but remains poor in countries where access to care is less favorable.

Investigating new serological and tissue markers for the follow-up of patients operated for alveolar echinococcosis.

AIMS: Alveolar echinococcosis (AE) is characterized by a chronically progressing hepatic injury caused by Echinococcus multilocularis. Surgery presently remains the best curative option. Currently, biological predictive features derived from the resected specimens are not suitable to assess surgery efficacy. The present study was designed to investigate whether a selection of markers measured on the resected specimens exhibits predictive features related to parasite viability, or to a total elimination of the parasite, in addition to serological markers. METHODS AND RESULTS: In a collaboration between two centres, one in France (Besançon), and one in Switzerland (Bern), samples from 40 AE patients were analysed by microarray and serology techniques, individually. Paired serum samples before and after surgery were obtained for 26 patients. In the sera, a significant decrease in PD-L1 levels was observed after surgery, in addition to anti-Em18 levels. In the liver tissue, low levels of Cluster of Differentiation (CD)-3 were correlated with the absence of serum anti-Em18 after surgery. CONCLUSION: This study showed PD-L1 is promising as a potential serological marker and further confirmed the performance of anti-Em18 serology. Further studies on a larger cohort are needed to confirm the utility of performing systematically microarray on resected liver tissue.

Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study.

BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases < 0.6 × ULN (OR = 7.1; CI: 1.3; 36.7). Thirty-nine patients stopped therapy after a median biochemical response of 48.6 months. Twenty-four of them had a biopsy before treatment withdrawal: 21 were histological responders. The cumulative rate of relapse was 25% at 64 months. CONCLUSIONS: This study indicates that older age, mild-to-moderate fibrosis at diagnosis and serum aspartate aminotransferases in the lower range of normal are independent predictors of histological response in AIH with prolonged biochemical response. The relapse rate after treatment withdrawal may be limited to 25% at 64 months when patients are selected on the basis of prolonged biochemical remission and, when available, histological response.

[Update on cystic echinococcosis of the liver]. / Actualités sur l'échinococcose kystique hépatique.

Hepatic cystic echinococcosis (HCE), is a cosmopolitan parasitic zoonosis. Autochtonous HCE cases are rare and the majority of cases are imported from endemic areas. It induces the development in the liver of Echinococcus granulosus larvae. Extrahepatic localizations are also possible. Cyst development is slow with an often-late diagnosis. In Switzerland, HCE discovery is usually fortuitous, during an abdominal radiological examination. More rarely, an acute clinical picture reveals a complication that can be severe or even fatal. The diagnosis is based on ultrasound findings that allows cyst characterization according to the WHO classification. This guides the therapeutic choice: simple monitoring, albendazole therapy, percutaneous procedures or surgery.

L'échinococcose kystique hépatique (EKH) est une zoonose parasitaire cosmopolite. Les cas d'EKH autochtones sont rares et la majorité est importée par des patients originaires de zones d'endémie. L'EKH est due au développement dans le foie de la larve d'Echinococcus granulosus. Des localisations extrahépatiques sont également possibles. Son évolution est lente avec un diagnostic fréquemment tardif. En Suisse, celui-ci est souvent fortuit, à l'occasion d'un examen radiologique abdominal. Plus rarement, un tableau clinique aigu et bruyant révèle une complication qui peut être sévère, voire mortelle. Le diagnostic basé sur l'échographie permet la caractérisation du kyste selon la classification de l'OMS. Celle-ci guide le choix thérapeutique: surveillance simple, traitement par albendazole, gestes percutanés ou chirurgie.

AE hepatic lesions: correlation between calcifications at CT and FDG-PET/CT metabolic activity.

PURPOSE: To correlate the presence of calcifications in alveolar echinococcosis (AE) hepatic lesions to the metabolic activity in 18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). METHODS: Our institutional review board approved this study. 61 patients (29 women, 32 men, aged from 15 to 86 years) were included in the study. Images of FDG-PET/CT were interpreted by two independent nuclear medicine physicians. AE hepatic lesions were classified as AE lesions with or without hypermetabolic activity. The presence of calcifications was assessed on unenhanced CT scans by two independent radiologists blinded with regard to the metabolic activity of the AE hepatic lesions. Every single calcification the size of which was < 3 mm and non-measurable calcifications which were forming areas with a powdery appearance were considered as microcalcifications. All other types of calcifications were reported as macrocalcifications. Statistical analysis was performed and p value < 0.05 was considered as statistically significant. RESULTS: Microcalcifications and macrocalcifications were present at CT in 95% (58/61) AE hepatic lesions and 43% (26/61) AE hepatic lesions, respectively. Hypermetabolic activity was present at FDG-PET/CT in 93% (57/61) AE hepatic lesions. 98% (56/57) of the AE hepatic lesions presenting with hypermetabolic activity at FDG-PET/CT showed microcalcifications at CT (p = 0.01) when only 40% (23/57) showed macrocalcifications at CT (p = 0.3). 100% (23/23) of the AE hepatic lesions with hypermetabolic activity at FDG-PET/CT and macrocalcifications at CT showed also microcalcifications at CT. CONCLUSIONS: Hypermetabolic activity of AE hepatic lesions at FDG-PET/CT is strongly correlated to the presence of microcalcifications at CT, independently of the presence of macrocalcifications.

Hints for control of infection in unique extrahepatic vertebral alveolar echinococcosis.

The prognosis of vertebral alveolar echinococcosis (AE) is poor. We report on the unique outcome of a patient with preexisting liver cirrhosis, in whom a diagnosis of vertebral AE was established on vertebral histopathology (D4 corporectomy in 2010 for paraplegia). Therapeutic drug monitoring of albendazole (ABZ) showed that a low dosage was appropriate. The patient recovered and ABZ withdrawal was decided in 2014, with no relapse 18 months later. In this patient, infection was purely or mainly localized in the dorsal spine, and this may have been favored by liver cirrhosis. A longer follow-up is, however, needed to confirm cure.

Alveolar echinococcosis: correlation between hepatic MRI findings and FDG-PET/CT metabolic activity.

OBJECTIVE: To correlate the appearance of alveolar echinococcosis (AE) hepatic lesions in magnetic resonance imaging (MRI) as defined by Kodama, to the metabolic activity visualized in 18-fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT). MATERIALS AND METHODS: Forty-two patients diagnosed with AE and who underwent both MRI and PET/CT were included. The forty-two hepatic lesions were divided into five types according to Kodama's classification by three independent readers blinded with regard to the PET/CT information. Concerning PET/CT, two independent readers, unaware of the MRI information, considered the results as positive when an increased FDG-uptake was observed at 1 or 3 h after FDG-injection, and as negative when no increased uptake was noted. Inter-observer agreement was assessed by using κ statistics. RESULTS: Forty-two lesions were counted and the mean diameter of overall evaluated lesions was 6.3 cm. One lesion (2.4%) was categorized as type 1, 11 (26.2%) as type 2, 24 (57.1%) as type 3, 3 (7.1%) as type 4, and 3 (7.1%) as type 5. The inter-observer analysis found a κ coefficient of 0.96. All type-1, 90.9% of type-2 and 87.5% of type-3 lesions showed an increased FDG-uptake on PET/CT images. All non-microcystic AE liver lesions (types 4 and 5) showed no abnormal increased FDG-uptake on PET/CT images. The inter-observer analysis at 1 and 3 h found a κ coefficient of 0.95 and 0.92, respectively. CONCLUSIONS: In patients with AE liver lesions, the absence of microcysts on MRI is strongly correlated to a metabolically inactive disease.

Increased incidence and characteristics of alveolar echinococcosis in patients with immunosuppression-associated conditions.

BACKGROUND: An increased incidence of alveolar echinococcosis (AE) in patients with immunosuppression (IS) has been observed; our aim was to study this association and its characteristics. METHODS: Fifty AE cases with IS-associated conditions (ISCs) before or at AE diagnosis were collected from the French AE registry (1982-2012, 509 cases). There were 30 cancers, 9 malignant hematological disorders, 14 chronic inflammatory diseases, 5 transplants, and 1 case of AIDS; 9 patients had ≥2 ISCs. Characteristics of the 42 IS/AE cases and the 187 non-IS/AE cases diagnosed during the period 2002-2012 were statistically compared. RESULTS: There was a significant increase in IS/AE cases over time. Risk factors did not differ between IS/AE and non-IS/AE patients. However, AE was more frequently an incidental finding (78% vs 42%) and was diagnosed at earlier stages (41% vs 23%) in IS/AE than in non-IS/AE patients. Serology was more often negative (14% vs 1%) and treatment efficacy was better (51% regression after 1-year treatment vs 27%) in IS/AE patients. All IS/AE patients but 7 took IS drugs; 7 received biotherapeutic agents. When not concomitant, AE occurred in IS patients within a 48-month median time period. Atypical presentation and abscess-, hemangioma-, and metastasis-like images delayed AE diagnosis in 50% of IS/AE patients, resulting in inappropriate treatment. Liver images obtained for 15 patients 1-5 years before diagnosis showed no AE lesions. Albendazole efficacy was good, but 19 of 48 treated patients experienced side effects. CONCLUSIONS: Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE.

Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis.

BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS: We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS: Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS: In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

Challenging the phylogenetic relationships among Echinococcus multilocularis isolates from main endemic areas.

Alveolar echinococcosis (AE) is a rare but severe disease that affects more than 18,000 people worldwide per year. The complete sequencing of the mitochondrial genome of Echinococcus multilocularis has made it possible to study the genetic diversity of the parasite and its spatial and temporal evolution. We amplified the whole mitochondrial genome by PCR, using one uniplex and two multiplex reactions to cover the 13,738 bp of the mitogenome, and then sequenced the amplicons with Illumina technology. In total, 113 samples from Europe, Asia, the Arctic and North America were analyzed. Three major haplogroups were found: HG1, which clustered samples from Alaska (including Saint-Lawrence Island), Yakutia (Russia) and Svalbard; HG2, with samples from Asia, North America and Europe; and HG3, subdivided into three micro-haplogroups. HG3a included samples from North America and Europe, whereas HG3b and HG3c only include samples from Europe. In France, HG3a included samples from patients more recently diagnosed in a region outside the historical endemic area. A fourth putative haplogroup, HG4, was represented by only one isolate from Olkhon Island (Russia). The increased discriminatory power of the complete sequencing of the E. multilocularis mitogenome has made it possible to highlight four distinct geographical clusters, one being divided into three micro-haplogroups in France.

Populations at risk for alveolar echinococcosis, France.

During 1982-2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84-117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21-464.51 for farmers and OR 6.98, 95% CI 2.88-18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82-10.91). These findings can help sensitization campaigns focus on specific groups.

Detecting nested clusters of human alveolar echinococcosis.

Recent changes in the epidemiology of alveolar echinococcosis (AE) in Eurasia have led to increasing concerns about the risk of human AE and the need for a thorough evaluation of the epidemiological situation. The aim of this study was to explore the use of a National Register to detect complex distribution patterns on several scales. The data were human AE cases from the FrancEchino register, diagnosed in France from 1982 to 2011. We used the Kulldorff spatial scan analysis to detect non-random locations of cases. We proposed an exploratory method that was based on the successive detection of nested clusters inside each of the statistically significant larger clusters. This method revealed at least 4 levels of disease clusters during the study period. The spatial variations of cluster location over time were also shown. We conclude that National Human AE registers, although not exempted from epidemiological biases, are currently the best way to achieve an accurate representation of human AE distribution on various scales. Finally, we confirm the multi-scale clustered distribution of human AE, and we hypothesize that our study may be a reasonable starting point from which to conduct additional research and explore the processes that underlie such distributions.

30-yr course and favorable outcome of alveolar echinococcosis despite multiple metastatic organ involvement in a non-immune suppressed patient.

We report the 30-yr history of a well-documented human case of alveolar echinococcosis, with a lung lesion at presentation followed by the discovery of a liver lesion, both removed by surgery. Subsequently, within the 13 years following diagnosis, metastases were disclosed in eye, brain and skull, as well as additional lung lesions. This patient had no immune suppression, and did not have the genetic background known to predispose to severe alveolar echinococcosis; it may thus be hypothesized that iterative multi-organ involvement was mostly due to the poor adherence to benzimidazole treatment for the first decade after diagnosis. Conversely, after a new alveolar echinococcosis recurrence was found in the right lung in 1994, the patient accepted to take albendazole continuously at the right dosage. After serology became negative and a fluoro-deoxy-glucose-Positron Emission Tomography performed in 2005 showed a total regression of the lesions in all organs, albendazole treatment could be definitively withdrawn. In 2011, the fluoro-deoxy-glucose-Positron Emission Tomography showed a total absence of parasitic metabolic activity and the patient had no clinical symptoms related to alveolar echinococcosis.The history of this patient suggests that multi-organ involvement and alveolar echinococcosis recurrence over time may occur in non-immune suppressed patients despite an apparently "radical" surgery. Metastatic dissemination might be favored by a poor adherence to chemotherapy. Combined surgery and continuous administration of albendazole at high dosage may allow alveolar echinococcosis patients to survive more than 30 years after diagnosis despite multi-organ involvement.

Alveolar echinococcosis in immunocompromised hosts.

BACKGROUND: Alveolar echinococcosis (AE) results of an infection with the larval stage of Echinococcus multilocularis. It has been increasingly described in individuals with impaired immune responsiveness. OBJECTIVES: This narrative review aims at describing the presentation of AE according to the type of immune impairment, based on retrospective cohorts and case reports. Implications for patient management and future research are proposed accordingly. SOURCES: Targeted search was conducted in PubMed using ((alveolar echinococcosis) OR (multilocularis)) AND ((immunosuppressive) OR (immunodeficiency) OR (AIDS) OR (solid organ transplant) OR (autoimmunity) OR (immune deficiency)). Only publications in English were considered. CONTENT: Seventeen publications were found, including 13 reports of 55 AE in immunocompromised patients (AE/IS) and 4 retrospective studies of 755 AE immunocompetent patients and 115 AE/IS (13%). The cohorts included 9 (1%) solid organ transplantation (SOT) recipients, 2 (0.2%) HIV patients, 41 (4.7%) with chronic inflammatory/autoimmune diseases (I/AID) and 72 (8.3%) with malignancies. SOT, I/AID and malignancies, but not HIV infection, were significantly associated with AE (odds ratios of 10.8, 1.6, 5.9, and 1.3, respectively). Compared to AE immunocompetent patients, AE/IS was associated with earlier diagnosis (PNM stages I-II: 49/85 (58%) vs. 137/348 (39%), p < 0.001), high rate of atypical imaging (24/50 (48%) vs. 106/375 (28%), p < 0.01), and low sensitivity of serology (19/77 (25%) vs. 265/329 (81%), p < 0.001). Unusually extensive or disseminated infections were described in SOT and I/AID patients. IMPLICATIONS: Patients who live in endemic areas should benefit from serology before onset of a long-term immunosuppressive therapy, even if the cost-benefit ratio has to be evaluated. Physicians should explain AE to immunocompromised patients and think about AE when finding a liver lesion. Further research should address gaps in knowledge of AE/IS. Especially, extensive and accurate records of AE cases have to be collected by multinational registries.

Complete mitochondrial exploration of Echinococcus multilocularis from French alveolar echinococcosis patients.

Alveolar echinococcosis (AE) is a parasitosis that is expanding worldwide, including in Europe. The development of genotypic markers is essential to follow its spatiotemporal evolution. Sequencing of the commonly used mitochondrial genes cob, cox1, and nad2 shows low discriminatory power, and analysis of the microsatellite marker EmsB does not allow nucleotide sequence analysis. We aimed to develop a new method for the genotyping of Echinococcus multilocularis based on whole mitochondrial genome (mitogenome) sequencing, to determine the genetic diversity among 30 human visceral samples from French patients, and compare this method with those currently in use. Sequencing of the whole mitochondrial genome was carried out after amplification by PCR, using one uniplex and two multiplex reactions to cover the 13,738 bp of the mitogenome, combined with Illumina technology. Thirty complete mitogenome sequences were obtained from AE lesions. One showed strong identity with Asian genotypes (99.98% identity) in a patient who had travelled to China. The other 29 mitogenomes could be differentiated into 13 haplotypes, showing higher haplotype and nucleotide diversity than when using the cob, cox1, and nad2 gene sequences alone. The mitochondrial genotyping data and EmsB profiles did not overlap, probably because one method uses the mitochondrial genome and the other the nuclear genome. The pairwise fixation index (Fst) value between individuals living inside and those living outside the endemic area was high (Fst = 0.222, P = 0.002). This is consistent with the hypothesis of an expansion from historical endemic areas to peripheral regions.

Alveolar echinococcosis in solid organ transplant recipients: a case series from two national cohorts.

Alveolar echinococcosis (AE) is a severe parasitic infection caused by the ingestion of Echinococcus multilocularis eggs. While higher incidence and faster evolution have been reported in immunosuppressed patients, no studies have been performed specifically on AE in transplant patients. We searched for all de novo AE cases diagnosed between January 2008 and August 2018 in solid organ transplant (SOT) recipients included in the Swiss Transplant Cohort Study and the FrancEchino Registry. Eight cases were identified (kidney = 5, lung = 2, heart = 1, liver = 0), half of which were asymptomatic at diagnosis. AE diagnosis was difficult due to the low sensitivity (60%) of the standard screening serology (Em2+) and the frequently atypical radiological presentations. Conversely, Echinococcus Western blot retained good diagnostic performances and was positive in all eight cases. Five patients underwent surgery, but complete resection could only be achieved in one case. Moreover, two patients died of peri-operative complications. Albendazole was initiated in seven patients and was well tolerated. Overall, AE regressed in one, stabilized in three, and progressed in one case, and had an overall mortality of 37.5% (3/8 patients). Our data suggest that AE has a higher mortality and a faster clinical course in SOT recipients; they also suggest that the parasitic disease might be due to the reactivation of latent microscopic liver lesions through immune suppression. Western blot serology should be preferred in this population. Finally, surgery should be considered with caution, because of its low success rate and high mortality, and conservative treatment with albendazole is well tolerated.

Title: Échinococcose alvéolaire chez les receveurs d'une greffe d'organe solide : une série de cas de deux cohortes nationales. Abstract: L'échinococcose alvéolaire (EA) est une maladie parasitaire grave causée par l'ingestion d'œufs d'Echinococcus multilocularis. Bien qu'une plus haute incidence et une évolution plus rapide aient été rapportées chez les patients immunodéprimés, aucune étude n'a été conduite spécifiquement sur cette maladie chez les patients transplantés. Nous avons donc listé tous les cas d'échinococcose alvéolaire apparus de novo entre janvier 2008 et août 2018 chez les patients transplantés d'organe solide inclus dans la cohorte Swiss Transplant Cohort Study et le registre FrancEchino. Huit patients ont été identifiés (rein = 5, poumon = 2, cœur = 1, foie = 0), dont la moitié était asymptomatique au moment du diagnostic. Le diagnostic était compliqué par la basse sensibilité (60 %) de la sérologie standard de dépistage (Em2+) et par les présentations radiologiques atypiques des lésions. Les performances diagnostiques du Western Blot n'étaient toutefois pas affectées et ce test était positif chez tous les patients. Sur les cinq patients opérés, une résection complète n'a été possible que dans un cas, tandis que deux patients sont décédés dans les suites de l'opération. L'albendazole a été introduit chez 7 patients et a été bien toléré. Dans l'ensemble, l'EA s'est stabilisée dans 3 cas, a régressé dans un cas et a progressé dans un autre cas, avec une mortalité de 37,5 % (3/8 patients). Nos résultats suggèrent une mortalité plus élevée et une évolution plus rapide de l'EA chez les patients transplantés. Ils suggèrent aussi que la maladie parasitaire pourrait être due à la réactivation de lésions hépatiques microscopiques latentes à la faveur de l'immunosuppression. Le Western Blot devrait être préféré dans cette population. Finalement, la chirurgie devrait être envisagée avec prudence, étant donnés son faible taux de réussite, le nombre élevé de décès peri-opératoires et la bonne tolérance au traitement conservateur par albendazole.

Epidemiology, clinical features and management of autoimmune hepatitis in Switzerland: a retrospective and prospective cohort study.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.