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BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.
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Aim: To assess the role of granulocyte colony-stimulating factor (GCSF) in the patients with severe alcoholic hepatitis (SAH) using real world experience in the United States. Background: There are few effective treatments for severe alcoholic hepatitis, which has a significant fatality rate. GCSF has been associated with improved survival in a small number of Indian studies, while there is a dearth of information from other parts of the globe. Methods: We performed a single-center retrospective study of consecutive patients admitted to a tertiary care, liver transplant center with severe alcoholic hepatitis from May 2015 to February 2019. The patients receiving GCSF (5µg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to the patients receiving standard of care (n=42). Results: Thirty-day, 90-day and 1-year mortality rates was similar among groups (25% vs. 17%, P=0.58; 41% vs 29%, P=0.30; 41% vs 47%, P=0.44, respectively). There was no difference in liver transplant listing and orthotopic transplantation among groups. Conclusion: In this real-world, United States-based study, GCSF does not improved survival in the patient with several alcoholic hepatitis compared to standard of care.
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BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.
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COVID-19 , Hepatite Autoimune , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos Retrospectivos , Vacina BNT162 , Teste para COVID-19 , VacinaçãoRESUMO
BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.
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COVID-19 , Hepatite Autoimune , Preparações Farmacêuticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/tratamento farmacológico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.
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COVID-19 , Hepatite Autoimune , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , América , COVID-19/complicações , COVID-19/epidemiologia , Europa (Continente) , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Adulto JovemRESUMO
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative agent of coronavirus disease 2019 (COVID-19). The presenting symptoms of this virus are variable, and there is an increasing body of literature on risk factors for mortality. The aim of this study was to evaluate the effect of initial aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and preexisting liver disease, including cirrhosis, in a cohort of patients admitted with COVID-19 infection at a tertiary care hospital network in the Bronx, New York. We reviewed 3,352 patients who had a positive SARS-CoV2 nasal swab, were over 18 years of age, and had an associated inpatient admission and discharge (or death) to the Montefiore Medical Center from February 28, 2020, to May 22, 2020. Of these, 39/86 (45%) patients died when the initial ALT was >5 times the upper limit of normal (ULN); 115/230 (50%) patients died when the initial AST was >3 times the ULN. The mortality of patients without preexisting liver disease was 26.6% compared to a mortality rate of 29.5% in patients with liver disease. Subgroup analysis showed a mortality of 36.1% in the patients with cirrhosis. Cirrhosis conferred a hazard ratio for mortality of 1.67 (95% confidence interval, 1.09, 2.55; P = 0.019). The baseline Model for End-Stage Liver Disease score was not prognostic in the cirrhosis cohort. There was no statistical difference between mortality in patients with a history of compensated or decompensated cirrhosis. The most common cause of death in the cirrhosis cohort was respiratory failure. Conclusion: COVID-19 hepatitis may lead to poor outcomes in patients who are hospitalized for the disease. Patients with cirrhosis are at a higher risk of COVID-19-related mortality.
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Alanina Transaminase/análise , Aspartato Aminotransferases/análise , COVID-19/mortalidade , Cirrose Hepática/complicações , Fígado/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Estudos de Coortes , Feminino , Hospitalização , Humanos , Fígado/virologia , Masculino , Pessoa de Meia-Idade , New York , Prognóstico , Insuficiência Respiratória , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Centros de Atenção TerciáriaAssuntos
Infecções por Coronavirus , Coronavirus , Transplante de Fígado , Pandemias , Pneumonia Viral , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2RESUMO
Ibrutinib, an inhibitor of the Bruton's tyrosine kinase of the B-cell receptor pathway, is an effective therapeutic agent for B-cell lymphomas. As these drugs are novel, long-term or rare adverse events are not yet known. We report the first case of ibrutinib-induced severe liver injury in a patient with relapsed/refractory CLL.
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CONTEXT: Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. EVIDENCE ACQUISITION: The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. RESULTS: Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. CONCLUSIONS: Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.
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AIM: We hypothesized that AIH outcomes might be different in our patient population that consists of a large number of Latinos. BACKGROUND: Literature has suggested that the presentation and outcome of autoimmune hepatitis can be different among different ethnicity and communities. PATIENTS AND METHODS: We performed a retrospective chart review of Latino patients with AIH diagnosed between 2002-2012. Complete and partial remissions were defined as normalization of liver enzyme values, or achieving less than twice the upper limit normal (ULN), respectively. RESULTS: A total of 28 patients were identified. 26 (93%) were female. 13 (46%) had an acute presentation, one with type 2 AIH and 3 with ANA seronegative disease. The average pathologic stage (Ishak score) was 3.44±1.67 (range: 0-6). Complete and partial remission was achieved in 20 (71%) and 5 (18%) patients respectively. Ten patients (38%) required maintenance prednisone either alone (2), or in combination with Azathioprine (6) or Mycophenolate Mofetil (2). Remission in the majority of patients, including 14 (50%) who were cirrhotic. Six of 14 (43%) cirrhotic patients were asymptomatic at the time of diagnosis. CONCLUSION: In an urban Latino population, cirrhosis was the initial presentation of AIH in a significant percentage of patients raising concerns regarding insufficient screening for AIH in this patient population. A large number of patients required continuous prednisone to avoid relapse.
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OBJECTIVES: Although effective, direct acting antiviral (DAA) therapies for genotype 1 (GT 1) hepatitis C virus (HCV) have been associated with compliance challenges. Additionally, treatment at predominantly community-based centers has been associated with low retention of patients on treatment and higher dropout rates. The OPTIMAL Phase IV interventional trial (ClinicalTrials.gov Identifier: NCT01405027) was designed to evaluate the impact of an education program for community investigator (CI) sites participating in a Chronic Liver Disease Foundation study treating chronic GT 1 HCV patients. METHODS: This physician educational program was administered by 22 Hepatology Centers of Educational Expertise (HCEE) academic sites to 33 CI sites asked to participate from December 2011 to July 2012. The HCEE mentors from DAA-experienced academic sites educated those at CI sites on therapeutic management, practice, and patient outcomes through a series of four standardized educational sequence visits regarding the use of first generation HCV protease inhibitors and the overall treatment of HCV. RESULTS: Treatment duration compliance rates for patients treated at CI sites versus those treated at HCEE academic sites were evaluable in 77 of 84 HCEE academic site patients, 102 of 113 patients treated at CI sites, and 179 of 197 overall patients. The treatment duration compliance rates for patients treated at HCEE academic sites, CI sites and overall were 85.4 ± 25.39%, 83.8 ± 27.37%, and 84.5 ± 26.48%, respectively, and did not differ statistically between the groups (p = 0.49). Almost half (47%) of the patients in the study achieved a sustained virological response for 24 weeks (SVR24) regardless of the type of site (p = 0.64). Safety profiles were similar at both HCEE and CI sites. CONCLUSIONS: These results demonstrated that education of CI sites unfamiliar with DAAs resulted in patient outcomes consistent with those observed at DAA-experienced academic sites.
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Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologia , Adulto , Feminino , Humanos , Derivação Portossistêmica Transjugular Intra-Hepática , Veia Esplênica/diagnóstico por imagem , Veia Esplênica/cirurgia , Stents , Trombectomia , Trombose/complicações , Trombose/diagnóstico por imagem , Trombose/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Chronic hepatitis B continues to be a major global health burden. It accounts for a substantial impact on health care resources and finances in many parts of the world including Europe. Natural history and disease spectrum are varied, depending on when and how the infection is acquired. The chronic infective state increases patients' risk of progression to liver cirrhosis or hepatocellular carcinoma. Several treatment options are currently available, but their use depends on the stage of the patient's infection, which is influenced by both host and viral factors. The ultimate goals in hepatitis B treatment are to prevent disease progression, hepatic decompensation, hepatocellular carcinoma, and death. Patients with decompensated liver cirrhosis should be referred to specialized transplant centers in a timely manner.
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Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/virologia , Transplante de Fígado , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody-negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients.
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Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Hepatite C/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Saúde da População UrbanaRESUMO
BACKGROUND: To lessen the severity of recurrent hepatitis C virus (HCV) postliver transplantation (post-LT) by treating HCV patients with cirrhosis, we assessed the safety and efficacy of an escalating dose pegylated interferon (PEG-IFN)/ribavirin protocol in pre-LT patients. METHODS: Ninety patients were treated with 90 microg PEG-IFN alpha-2a and 400 mg ribavirin and advanced to 180 microg and 800 to 1200 mg, respectively, over 8 weeks. RESULTS: Mean age was 55.3 years. Thirty-four percent of patients received prior interferon treatment, 77% had genotype 1 or 4. Mean Child's score was 6.7 and model for end-stage liver disease 11.2; 49% reached full-dose PEG-IFN and 85% ribavirin, 18% required dose reduction, 33% stopped treatment because of adverse effects, 9% had deterioration of liver function, and 7% died. Follow-up of 9.6 months showed sustained virological response in 13% of patients. The rate of serious complications was 16.3% in Child's class A, 48% in B, and 100% in C (P=0.005). Serum albumin was a significant predictor for worsening liver function (P=0.007). CONCLUSIONS: Using an escalating dose regimen of PEG-IFN alpha-2a and ribavirin, we achieved only a 13% sustained virological response in HCV cirrhotic pre-LT patients with an accompanying 9% risk of worsening liver function and 7% risk of death.
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Antivirais/uso terapêutico , Hepacivirus/metabolismo , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Interferon-alfa/uso terapêutico , Cirrose Hepática/terapia , Transplante de Fígado/métodos , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Esquema de Medicação , Feminino , Genótipo , Humanos , Interferon alfa-2 , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Resultado do TratamentoRESUMO
Laparoscopic cholecystectomy is commonly performed as the treatment of choice for symptomatic gallstone diseases. Bile leak is a potential complication of this procedure and the cystic duct stump is the most common site of leakage. Early diagnosis and treatment of bile leak is crucial in decreasing the morbidity and mortality related to this complication. Endoscopic retrograde cholangiopancreatography with stent placement and/or sphincterotomy is highly effective in the diagnosis and treatment of this problem.