Real-World Effectiveness and Safety of Glecaprevir/Pibrentasvir for the Treatment of Chronic Hepatitis C: A Prospective Cohort Study in Portugal.

INTRODUCTION: Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice. METHODS: An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97). RESULTS: Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB. CONCLUSION: Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).

Extremely giant liver hemangioma: a case beyond the norms.

A 68-year-old overweight woman with no history of oral contraceptive use presented a large liver mass of 40 cm on abdominal ultrasound without associated symptoms. Complete blood count, coagulation study, and liver biochemistry were unremarkable. Abdominal contrast-enhanced CT revealed a 33x24 cm lesion with discontinuous peripheral globular uptake and centripetal fill-in, consistent with an extremely giant hemangioma. It affected all segments of the right lobe, compressing the right suprahepatic vein and displacing all intra-abdominal structures, with a deviation of the midline structures (stomach and pancreas) to the left. Given the hemangioma size and its significant mass effect, surgery was discussed but declined by the patient, who remains asymptomatic 3 years later. Extremely giant liver hemangiomas (>10 cm) are rare, and the approach to asymptomatic patients is debated. Some advocate for prophylactic excision due to the potential for internal bleeding, growth, or rupture, while others suggest intervention for hemangiomas near major vascular structures. The American College of Gastroenterology recommends surgical intervention in such cases, but the European Association for the Study of the Liver suggests a conservative approach for most patients. This case highlights a successful "watch-and-wait" strategy, bringing attention to this unusual condition and its controversial management.

Tofacitinib-induced eosinophilia.

Tofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data. We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia. Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about an adverse reaction to tofacitinib not reported so far, including in a multicenter real-life setting recently published by Hernández et al where eosinophilia is also not described, thus emphasizing the rarity of this AE. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC. .

A Rare Cause of Abdominal Pain: IgG4-Related Sclerosing Mesenteritis.

A 67-year-old man with previous cardiovascular disease was referred to our consultation due to a 5-month history of recurrent epigastric pain. Esophagogastroduodenoscopy and full blood workup presented no alterations. CT scan showed an irregularly shaped mass at the root of the mesentery, measuring 40x25x47mm, with spiculated contours and retractile behaviour (a). Simultaneous densification of the adjacent fat and infracentimetric ganglionic formations scattered throughout the mesentery were shown. Surgical biopsy revealed extensive storiform fibrosclerosis, with the presence of interstitial lymphoplasmocytic infiltrate and obliterative phlebitis (b); the plasma cells had mostly IgG expression, with IgG4:IgG ratio >40% (c), accounting for more than 30- 40 IgG4 plasma cells per field. The serum IgG4 level was 137mg/dL. A diagnosis of IgG4-related sclerosing mesenteritis was made, without other organ involvement. Prednisolone (0.6mg/kg/d) improved partially the abdominal pain, so steroid sparing strategy with off-label rituximab was associated. Due to its low prevalence, the understanding of this entity is scarce, and its diagnosis is challenging. Unlike other manifestations of IgG4-related disease, the intra-abdominal disease is identified in later stages, due to unspecific symptoms. This case aims to raise awareness about this condition as a differential diagnosis of abdominal pain.

Positioning Aeromonas Infection in Inflammatory Bowel Disease: A Retrospective Analysis.

Background and Aim: Aeromonas are Gram-negative rods known to cause a spectrum of diseases. Inflammatory bowel disease (IBD) is an idiopathic complex condition resulting from interaction of multiple factors. Aeromonas infection in association with IBD is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients. Methods: A retrospective observational analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a tertiary and university hospital. Results: Fifty patients were included, 56% male with a mean age of 42.1 years. Thirty-eight (76%) were non-IBD and 12 (24%) IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% developed mild, 44% moderate, and 16.7% severe infection. The main strains isolated were Aeromonas hydrophila/caviae. Bacterial co-isolation was found in 4 non-IBD and histological findings of cytomegalovirus in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in the IBD group. From IBD, 4 patients had the diagnosis of ulcerative colitis and 9 of Crohn's disease with colonic involvement. Of these patients, 5 received IBD diagnosis after the acute episode of Aeromonas infection. Conclusions: Clinical presentation of Aeromonas infection differs between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seems to greatly contribute to IBD manifestation.

Introdução: A etiologia da Doença Inflamatória Intestinal (DII) é complexa e resultante da interação de diversos fatores, nomeadamente microbiológicos. A infeção por Aeromonas caracteriza-se por um espectro alargado de manifestações clínicas. O papel da infeção por Aeromonas na DII não está caracterizado. Objetivos: Avaliar o significado da infeção por Aeromonas na DII e as diferenças com a infeção em doentes não-DII. Métodos: avaliação retrospetiva e observacional de todos os doentes com isolamento microbiológico de Aeromonas em amostras fecais num período de 10 anos, num hospital terciário. Resultados: foram avaliados 50 doentes, 56% do sexo masculino, com idade média de 42.1 anos. Doze (24%) com diagnóstico de DII e trinta e oito (76%) não-DII. Os doentes com DII encontravam-se mais frequentemente sob imunossupressão. Dois doentes foram assintomáticos, 44% desenvolveram doença ligeira, 44% moderada e 16.7% severa, havendo maior tendência para infeção severa nos DII. Os doentes não-DII apresentaram mais frequentemente febre e os DII diarreia sanguinolenta e dor abdominal. O uso de antimicrobianos foi superior no grupo DII e a utilização de corticoesteroides foi exclusiva nestes doentes. Isolamento concomitante de outros agentes microbiológicos ocorreu em 4 doentes não-DII e 2 com DII tinham histologia compatível com infeção por Citomegalovírus. Da população DII, 4 eram Colite Ulcerosa e 9 Doença de Crohn com envolvimento cólico. Destes, 5 receberam o diagnóstico após a infeção por Aeromonas. Conclusão: A apresentação clínica da infeção por Aeromonas foi distinta entre as populações DII e não-DII, sendo que os doentes DII apresentaram doença mais severa e maior utilização de antimicrobianos. A infeção na DII ocorreu essencialmente em doentes com envolvimento cólico.

Hemostatic spray as a therapy for pancreatic stump bleeding after cephalic duodenopancreatectomy.

A 70-year-old man with a cholangiocarcinoma underwent a cephalic duodenopancreatectomy. On the 2nd postoperative day, he had hematemesis without hemodynamic instability. Upper endoscopy (EGD) revealed a massive clot at the pancreatic stump, suspected as the source of hemorrhage. After partial clot removal, no active bleeding was found and no therapy was performed. Pancreaticogastric and gastrojejunal anastomoses, as well as the efferent-limb, showed no suspicious lesions. Octreotide was initiated and heparin prophylaxis was temporarily stopped. Bleeding from pancreatic stump following pancreatoduodenectomy is a rare but a life-threatening condition. Conventional endoscopic therapies, including clip placement and cautery, are mostly ineffective and with high risk of pancreatitis. We report the second case of hemostatic powder as a safe and successful therapy in this scenario.

Gastric barotrauma induced by the Sellick maneuver performed to enable endoscopic submucosal dissection

A 55-year-old male underwent endoscopic submucosal dissection (ESD), under general anesthesia and orotracheal intubation, of a 22 mm Paris 0-IIa+0-IIb lesion located in the greater curvature of the medium/distal antrum. It was not possible to start the procedure after several attempts due to permanent belching and inability to maintain adequate gastric distension. ESD was only feasible after performing the Sellick maneuver (manual pressure application at the cricoid cartilage to occlude the upper esophagus), which allowed sustained gastric distension throughout the procedure (60 minutes). (AU)

Endoscopic submucosal dissection: a country dissemination experience and outcomes.

OBJECTIVE: An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal. METHODS: All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center. RESULTS: All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81-96.8) and 87% (IQR, 74-93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25-6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions. CONCLUSION: Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.

Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome.

Lynch Syndrome is characterized by phenotypic and genotypic heterogeneity. Despite scarce evidence, individuals with an EPCAM deletion appear to have a comparable risk of colorectal cancer (CRC) as MSH2 mutation carriers, but a lower risk of extracolonic cancer (such as endometrial cancer) unless the deletion extends close to the promoter of MSH2. A genotype-phenotype correlation is yet to be established for EPCAM alterations. In this report, we describe a family with EPCAM deletion characterized by a particularly aggressive phenotype and extracolonic cancer. We present a family with 5 members carrying an EPCAM deletion encompassing exons 8 and 9. Three female family members presented CRC at the ages of 32, 44 and 60 (mucinous moderately and well-differentiated adenocarcinoma); in two of them metachronous colon cancers and advanced adenomas were diagnosed in the intensive surveillance program. Two female patients (42 and 63 years-old) presented with gastric cancer (GC). Two patients presented with small bowel cancer at 51 and 60 years-old - the first one presented a metachronous jejunal cancer at 68 years. Only one family member was submitted to hemithyroidectomy due a right-lobe Hürthle cell carcinoma at 56 years-old. This report illustrates the existence of intrafamilial clinical heterogeneity among carriers of this EPCAM alteration, and hence the difficulty in predicting phenotype for EPCAM-associated Lynch syndrome.

Hemochromatosis and Xeroderma Pigmentosum: Two (Un)Suspicious Neighbors.

A 51-year-old woman, clinically diagnosed with Xeroderma pigmentosum (XP), showed abnormalities in liver enzymes, high ferritin and transferrin saturation levels, with ultrasonographic features of chronic liver disease, in addition to skin hyperpigmentation. Genetic testing confirmed the clinical hypothesis of hereditary hemochromatosis (HH). Due to the known proximity of HFE (6p22.2) and POLH (6p21.1) genes, accountable for HH and the XP-V variant, respectively, a genetic test was offered and a rare variant of the POLH gene was identified. We report the first confirmed case, to our knowledge, of a patient diagnosed both with XP and HH, in whom two mutated neighbor genes - POLH and HFE - were identified, possibly the result of genetic linkage.

Uma mulher de 51 anos, com antecedentes pessoais de Xeroderma pigmentosum (XP), apresentava, além de hiperpigmentação cutânea, alterações nas enzimas hepáticas, elevação da ferritina sérica e da saturação da transferrina, bem como alterações ecográficas compatíveis com doença hepática crónica. A realização de um teste genético permitiu confirmar a hipótese diagnóstica de Hemocromatose Hereditária (HH). Pela proximidade conhecida dos genes HFE (6p22.2) e POLH (6p21.1), responsáveis pela HH e pelo XP-V, respetivamente, foi realizado um teste genético que detetou um polimorfismo raro do gene POLH. Reportamos o primeiro caso de uma paciente diagnosticada com XP e HH, na qual foram identificados dois genes vizinhos mutados ­ POLH e HFE ­, possivelmente como resultado de ligação genética.

Gastric barotrauma induced by the Sellick maneuver performed to enable endoscopic submucosal dissection.

A 55-year-old male underwent endoscopic submucosal dissection (ESD), under general anesthesia and orotracheal intubation, of a 22 mm Paris 0-IIa+0-IIb lesion located in the greater curvature of the medium/distal antrum. It was not possible to start the procedure after several attempts due to permanent belching and inability to maintain adequate gastric distension. ESD was only feasible after performing the Sellick maneuver (manual pressure application at the cricoid cartilage to occlude the upper esophagus), which allowed sustained gastric distension throughout the procedure (60 minutes).

Polidocanol Foam Sclerotherapy Versus Rubber Band Ligation in Hemorrhoidal Disease Grades I/II/III: Randomized Trial.

BACKGROUND: Rubber band ligation and sclerotherapy are considered the office-based procedures of choice in hemorrhoidal disease. However, there are no studies comparing rubber band ligation and polidocanol foam sclerotherapy. OBJECTIVE: We aimed to evaluate the efficacy and safety of polidocanol foam sclerotherapy compared with rubber band ligation. DESIGN: This study was a randomized open-label study with 1-year follow-up. SETTINGS: The study was conducted in the colorectal unit of a tertiary hospital. PATIENTS: One hundred twenty patients with hemorrhoidal disease grades I to III were included. INTERVENTIONS: Patients were stratified by hemorrhoidal disease grade and randomly assigned (1:1) to treatment with either rubber band ligation (n = 60) or polidocanol foam sclerotherapy (n = 60). MAIN OUTCOME MEASURES: Efficacy outcomes included therapeutic success and recurrence. Safety outcomes included the occurrence of complications related to the procedures. RESULTS: Therapeutic success was not significantly different between the groups (polidocanol foam sclerotherapy 93.3% vs rubber band ligation 85.0%, p = 0.14). However, complete success rate was higher in the polidocanol foam sclerotherapy group (88.3% vs 66.7%, p = 0.009) with fewer office-based sessions (mean ± SD: 1.32 ± 0.60 vs 1.62 ± 0.76, p = 0.02). Recurrence rates were lower in the polidocanol foam sclerotherapy group (16.1% vs 41.2%, p = 0.004). Most recurrences were mild (83.3%). Complications were more frequent in the rubber band ligation group (30.0% vs 10.0%, p = 0.01) and were mostly minor (91.7%). No severe complications were observed in either group. LIMITATIONS: This study was performed in a single center, and both patients and investigators were not blinded to the treatment group. CONCLUSIONS: Both procedures are effective in the treatment of hemorrhoidal disease grades I to III. Polidocanol foam sclerotherapy was more effective than rubber band ligation when considering complete success. Patients in the polidocanol foam sclerotherapy group needed fewer treatment sessions, had lower recurrence rates, and were less likely to have complications. See Video Abstract at http://links.lww.com/DCR/B816. REGISTRATION: https//www.clinicaltrials.gov; Identifier: NCT04091763. ESCLEROTERAPIA CON ESPUMA DE POLIDOCANOL VERSUS LIGADURA CON BANDA DE GOMA EN LOS GRADOS I / II / III DE ENFERMEDAD HEMORROIDAL ENSAYO ALEATORIZADO: ANTECEDENTES:La ligadura con banda elástica y la escleroterapia se consideran los procedimientos de elección en el consultorio para la enfermedad hemorroidal. Sin embargo, no hay estudios que comparen la ligadura con bandas elastica y la escleroterapia con espuma de polidocanol.OBJETIVO:Nuestro objetivo fue evaluar la eficacia y seguridad de la escleroterapia con espuma de polidocanol en comparación con la ligadura con bandas elastica.DISEÑO:Estudio aleatorizado randomizado, abierto, con seguimiento de 1 año.AJUSTES:El estudio se realizó en una unidad colorrectal de un hospital terciario.PACIENTES:Se incluyeron 120 pacientes con enfermedad hemorroidal grados I a III.INTERVENCIONES:Los pacientes fueron estratificados por grado de enfermedad hemorroidal y asignados al azar (1: 1) al tratamiento con ligadura con banda elastica (n = 60) o escleroterapia con espuma de polidocanol (n = 60).PRINCIPALES MEDIDAS DE RESULTADO:Los resultados de eficacia incluyeron el éxito terapéutico y la recurrencia. Los resultados de seguridad incluyeron la aparición de complicaciones relacionadas con los procedimientos.RESULTADOS:El éxito terapéutico no fue significativamente diferente entre los grupos (escleroterapia con espuma de polidocanol 93,3% vs ligadura con banda de goma 85,0%, p = 0,14). Sin embargo, la tasa de éxito completo fue mayor en el grupo de escleroterapia con espuma de polidocanol (88,3% vs 66,7%, p = 0,009), con menos sesiones en el consultorio (media ± desviación estándar: 1,32 ± 0,60 vs 1,62 ± 0,76, p = 0,02). Las tasas de recurrencia fueron más bajas en el grupo de escleroterapia con espuma de polidocanol (16,1% vs 41,2%, p = 0,004). La mayoría de las recurrencias fueron leves (83,3%). Las complicaciones fueron más frecuentes en el grupo de ligadura con bandas elastica (30,0% vs 10,0%, p = 0,01) y fueron en su mayoría menores (91,7%). No se observaron complicaciones graves en ninguno de los grupos.LIMITACIONES:Este estudio se realizó en un solo centro y ni los pacientes ni los investigadores estaban cegados al grupo de tratamiento.CONCLUSIONES:Ambos procedimientos son efectivos en el tratamiento de la enfermedad hemorroidal grados I a III. La escleroterapia con espuma de polidocanol fue más eficaz que la ligadura con banda de goma cuando se consideró el éxito completo. Los pacientes del grupo de escleroterapia con espuma de polidocanol necesitaron menos sesiones de tratamiento, tuvieron tasas de recurrencia más bajas y menos probabilidades de tener complicaciones. Consulte Video Resumen en http://links.lww.com/DCR/B816. (Traducción-Dr Yolanda Colorado)ClinicalTrials.gov, número NCT04091763.

Colorectal Screening Program in Northern Portugal: First Findings.

INTRODUCTION: In Portugal, a colorectal cancer screening program based on faecal immunochemical test followed by colonoscopy was shown to be cost-effective for individuals between 50 and 74 years old. We report the first findings of the implementation of a population-based program In Northern Portugal. MATERIAL AND METHODS: In the pilot phase, eligible subjects were allocated either to a direct mailing invitation or to primary care centers. In the first year of program implementation, we assessed the uptake rate, the faecal immunochemical test -positivity rate, the diagnostic yield of advanced neoplasia, and the quality parameters for post-faecal immunochemical test + colonoscopy. RESULTS: We invited 100 501 eligible subjects (49% male with a median age of 55 years). Of these, 5228 participated in the pilot phase and 95 273 participated in the first year of the program. In the first year of the program, the adherence was 29%, with a positivity rate of 5% and a 60% compliance to colonoscopy. The faecal immunochemical test-detection rate of advanced neoplasia was 0.35/1000 subjects, and the positive predictive value at post- faecal immunochemical test + colonoscopy was 44% and 2% for advanced adenoma and invasive cancer, respectively. No major adverse events were reported after colonoscopy. DISCUSSION: The suboptimal adherence to faecal immunochemical test and post-faecal immunochemical test + colonoscopy remains the most urgent step to be addressed. CONCLUSION: A centralized invitation system based on direct mailing was feasible and both colonoscopy quality and diagnostic yield were adequate antecipating the success of the programme.

Introdução: Em Portugal, foi demonstrado que o rastreio do cancro colo-rectal, baseado no teste imunoquímico fecal seguido de colonoscopia, seria custo-efetivo para indivíduos entre os 50 e 74 anos. Neste artigo reportamos os primeiros resultados da implementação do programa de base populacional na região Norte de Portugal. Material e Métodos: Na fase piloto, os sujeitos elegíveis foram alocados a dois métodos, por convite através do correio ou por meio de entrega direta nos centros de saúde. No primeiro ano de implementação do programa avaliámos a taxa de adesão, a taxa de positividade de teste imunoquímico fecal, o rendimento diagnóstico de neoplasia avançada e os parâmetros de qualidade da colonoscopia pós- teste imunoquímico fecal positivo. Resultados: Foram convidados 100 501 indivíduos elegíveis (49% do sexo masculino com idade mediana de 55 anos). Destes, 5228 participaram na fase piloto e 95 273 participaram no primeiro ano do programa. No primeiro ano do programa, a adesão foi de 29%, com taxa de positividade de 5% e adesão de 60% às colonoscopias. A taxa de deteção de teste imunoquímico fecal de neoplasia avançada foi de 0,35/1000 indivíduos, e o valor preditivo positivo na colonoscopia pós-teste imunoquímico fecal positivo foi de 44% e 2% para adenoma avançado e cancro invasivo, respetivamente. Não foi relatado nenhum evento adverso após colonoscopia. Discussão: A adesão subótima a teste imunoquímico fecal e colonoscopia pós-teste imunoquímico fecal continua a ser a etapa mais problemática. Conclusão: Um sistema de convite centralizado foi viável, a qualidade das colonoscopias realizadas e o rendimento diagnóstico adequados antecipando o sucesso do programa.

The wide phenotypic and genetic spectrum of ABCB4 gene deficiency: A case series.

BACKGROUND: ABCB4-gene mutations are responsible for several cholestatic diseases with a heterogeneous clinical spectrum. AIMS: To analyse phenotype/genotype relationships in ABCB4-mutations. METHODS: Retrospective characterization of adult patients with ABCB4-variations diagnosed between 2015 and 2020. Genotype-phenotype correlations were analysed and compared with previously reported data. RESULTS: Twenty patients from 12 families were included. Thirteen patients presented recurrent elevated liver tests, eight fulfilled Low-Phospholipid-Associated-Cholelithiasis syndrome criteria, five had Intrahepatic Cholestasis of Pregnancy and three patients developed Drug-Induced-Liver-Injury. ABCB4 screening identified eight different mutations. Five patients were homozygotes to the variant c.504T > C. Ten patients had one mutation in heterozygote-state and five patients had two mutations in compound-heterozygosity. Portal fibrosis occurred in two patients. One of these patients presented progressive fibrosis and progression of cholestasis despite ursodeoxycholic-acid treatment, this patient also harbours a ABCB11 polymorphism. CONCLUSION: Although, phenotype-genotype relationships have not been clearly defined, an early diagnosis of ABCB4-variants may have an important role in management decisions and patient outcomes. To our knowledge, we describe a not previously reported deletion (c.1181delT) in ABCB4. The c.504T > C polymorphism, although a silent mutation at the protein level, seems to be associated to different cholestatic diseases. The role of other genes variants, namely ABCB11, as co-factor for progression, needs to be clarified.