Antimigration versus conventional fully covered metal stents in the endoscopic treatment of anastomotic biliary strictures after deceased-donor liver transplantation.

INTRODUCTION: Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS. METHODS: Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates. RESULTS: A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28). CONCLUSIONS: The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed.

The impact of obesity on postoperative complications and short-term survival after liver transplantation.

BACKGROUND AND AIMS: Obesity is considered a risk factor for perioperative complications, but its effect on patients undergoing liver transplantation (LT) remains unclear. This study was conducted to analyze the impact of obesity on early morbidity and mortality risk following LT. METHODS: A multicenter study of outcomes in patients submitted to LT between 2009 and 2019 was conducted. Recipients were stratified into obese (BMI ≥ 30 kg/m2) and nonobese patients (BMI < 30 kg/m2). Early postoperative complications were compared and 30-day and 1-year patient and graft survival were assessed by Kaplan-Meier method. Primary graft nonfunction (PGNF) was defined as the presence of total bilirubin > 10 mg/dl, INR > 1.6 or ALT > 2000 U/l within the first week after LT. RESULTS: A total of 1608 patients were included after applying exclusion criteria, nonobese (1149, 71.46%) and obese patients (459, 28.54%). There were no significant differences in age, sex, Model for End-stage Liver Disease, Charlson comorbidity score, ethnicity, waiting list time and ischemia time. There were significantly higher rates of vascular (17.58% vs 23.53%, P = 0.021) and biliary complications (27.68% vs 35.73%, P = 0.006) and PGNF (11.40% vs 12.20%, P = 0.021) in obese patients. There was a significantly increased risk for long-term graft failure; however, there was no significant difference in patient survival after LT. CONCLUSION: Obese patients have significantly increased morbidity in terms of vascular and biliary complications and PGNF after LT. They have a higher risk for worse 1-year graft survival in comparison to controls.

DRESS syndrome secondary to carbamazepine.

DRESS syndrome is a multisystem disorder that appears in the context of an adverse drug reaction, characterized by fever, rash and peripheral eosinophilia with involvement of other organs such as the liver. The typical liver involvement is acute toxic hepatitis (DILI), showing improvement and a tendency to resolution when corticotherapy is started. We must not forget this manifestation in the clinical context of a DRESS syndrome.

Postreperfusion Biopsy as a Predictor of Biliary Complication After Deceased Donor Liver Transplantation. A Retrospective Cohort Study.

BACKGROUND: Ischemia reperfusion injury (IRI) on postreperfusion biopsies is associated with worse outcomes after liver transplantation, although the influence on biliary complications (BC) remains poorly studied. Therefore, the primary aim of our study was to assess the influence of IRI on the incidence of BC. A secondary aim was to assess the influence of steatosis on biliary complications and determine factors that predictor BC. METHODS: We report a retrospective cohort study including patients with liver transplantation and postreperfusion injury. Biopsies were classified as relevant and nonrelevant ischemia reperfusion injury for assessment of BC. BC included anastomotic stricture, ischemic cholangiopathy, leaks, and bilomas. Independent predictive factors of biliary complications were assessed using univariate and multivariate analyses. RESULTS: 302 patients were included, and 125 patients fulfilled the criteria for relevant IRI (41.4%). Worse IRI was not associated with biliary complications (42.5% vs 40.1%; P = .68), nor was liver graft steatosis associated with BC (40.5% vs 41.5%, P = .95). The median time until biliary complications did not differ between the 2 groups (2 months; interquartile range = 1-15 vs 3 months; interquartile range = 1-12.5; P = .18). Hepatic artery thrombosis (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.4-8.2; P = .004), older donor age (OR = 2.1; 95% CI, 1.1-4.1; P = .024), and prolonged cold ischemia time (OR = 1.9; 95% CI, 1.1-3.2) were independent factors of biliary complications. CONCLUSION: Severe IRI on the postreperfusion injury does not predict development of biliary complications.

Postreperfusion Liver Biopsy as Predictor of Early Graft Dysfunction and Survival After Orthotopic Liver Transplantation.

Background: Postreperfusion liver biopsy (PRB) can assess the degree of ischemia/reperfusion injury (IRI) after orthotopic liver transplantation (OLT). The influence of IRI on graft outcomes and overall survival is controversial. Aim: To determine the correlation between the severity of IRI in PRB and overall graft and patient survival and, secondarily, to identify factors on PRB that predict poor graft outcomes. Methods: This is a retrospective analysis of all patients who underwent OLT using donation after brain death (DBD) with PRB. The severity of IRI in PRB was graded. Predictors of IRI were assessed using univariate and multivariate analysis and the Kaplan-Meier with log rank test for the graft and overall survival, respectively. Results: We included 280 OLTs (64.7%). The histopathological assessment of IRI severity was as follows: no IRI (N = 96, 34.3%), mild IRI (N = 65; 23.2%), moderate IRI (N = 101; 36.1%), and severe IRI (N = 18; 6.4%). The incidence rates of initial good graft function (IGGF), primary nonfunction and early allograft dysfunction (EAD) were 32.5%, 3.9%, and 18.6%, respectively. Severe IRI was associated with a lower incidence of IGGF (OR: 0.34, 95% CI 0.12-0.92; P = 0.03). Patients with severe IRI tended to have a higher incidence of EAD (33.2% vs. 18.6, P = 0.23). The cold ischemia time was an independent predictor of severe IRI on the multivariate analysis. Severe IRI was associated with poor 1- and 5-year overall survival rates (67% and 44%, respectively, compared with 84 and 68% in nonsevere IRI). Patients with severe IRI exhibited worse graft and overall survival. Conclusions: Cold ischemia time predicts the development of severe IRI. Patients with severe IRI show worse graft and overall survival and a lower incidence of IGGF, suggesting that histopathological findings could be useful for identifying patients at high risk of worse outcomes after OLT.

Cecal ameboma and a liver abscess mimicking metastatic colonic cancer. An autochthonous infectious disease in Spain?

We present the case of 52 years-old male without any recent travel. He was admitted to our department for a history of fever and abdominal pain. A CT scan showed a cecal thickening and liver mass with suspected cecal carcinoma with infected necrotic liver metastasis. Although the colonoscopy revealed a bulky submucosal wall thickening with a fibrined ulcer with yellow granulating located in the cecum, the percutaneous drainage revealed a positive PCR for Entamoeba histolytica, with improvement with metronidazole treatment. Ameboma are ulcerative, exophytic, inflammatory masses up to 15 cm in diameter in patients with long standing colonic amoebic infections containing granulation tissue with pseudotumor appearance. It affects less than 1.5% of colonic invasive amebiasis. Moreover, concomitant hepatic amoebic can be observed up to 30%, mimicking colonic cancer with necrotic liver metastasis. Although no epidemiological risk factor for amoebic infection was detected. We therefore highlight the awareness of amoebic infection and different manifestation even in non-endemic areas.

Acute liver failure due to anti-tuberculous treatment: when you travel without medical follow-up.

We present an uncommon cause of liver transplant in a patient with a particular personal situation, who suffered loss of follow-up during his antitubercular treatment. He presented a dress syndrome with fulminant liver failure that required a liver transplant. This case demonstrates the importance of close monitoring of liver function during this treatment.

XI factor deficiency as cause of recurrent gastrointestinal bleeding.

We present the case of a 73-year-old woman with no relevant medical history. She was admitted for a 3-month intermittent melena. The physical exam was unremarkable. Blood tests revealed anemia (hemoglobin 7.4 g/dL), raised urea (69 mg/dL), normal platelets and coagulation. Gastroscopy was performed with active oozing bleeding in the fundus and gastric body. Endoscopic fulguration of the potential lesions with holmium laser was performed. She was discharged with resolution of the symptoms and analytical improvement. However, the patient required hospitalization two weeks later due to recurrence of melena and anemia.

COVID-19 and Short- and Medium-term Outcomes in Liver Transplant Patients: A Spanish Single-center Case Series.

BACKGROUND & AIMS: The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium- and short-term outcomes in liver transplant patients. PATIENTS AND METHODS: A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021 were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications, and liver graft function were assessed at diagnosis and 3-month follow-up. RESULTS: Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalized (50%) and 8 (50%) hospitalized patients were analyzed. The median follow-up was 5.33 months (IQR 3.06-8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnea and fatigue were the most prevalent symptoms during the 3-month follow-up. No liver graft dysfunction were reported despite of partial immunosuppression withdrawal in four patients (25%). One patient had cardiovascular complications. CONCLUSIONS: Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3 months after COVID-19. However, no cases of loss or liver graft dysfunction were reported.

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt / Resultados clínicos a largo plazo y predictores de la supervivencia de pacientes con cirrosis hepática tras inserción de prótesis recubierta transyugular intrahepática porto-sistémica dilatadas a 10mm

Background and aims: Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. Methods: This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan–Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. Results: A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/−9.9) and the median MELD was 13.3 (IQR 9.5–16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. Conclusions: TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.(AU)

Introducción: Los shunt intrahepático porto-sistémicos (TIPS) son utilizados con éxito en el tratamiento de las complicaciones de la hipertensión portal (HTP). Existe cierta controversia referente al diámetro dilatado. Los objetivos fueron analizar los resultados y las complicaciones derivadas de los TIPS en cirróticos, y determinar los factores predictores de la supervivencia. Métodos: Se trata de un estudio retrospectivo unicéntrico que incluyó pacientes cirróticos que recibieron un TIPS por HTP desde 2009 a octubre-2018. Se recogieron variables clínicas, demográficas y radiológicas. Se determinó la supervivencia mediante el método Kaplan-Meier y se identificaron los predictores de supervivencia con el modelo de regresión de Cox. Resultados: Se incluyeron 98 pacientes (78,6% varones). La media de edad fue de 58,5 años (DE ±9,9) y mediana de MELD 13,3 (RIC 9,5-16). Las indicaciones fueron ascitis refractaria (AR), hemorragia varicosa (HV) e hidrotórax hepático (HH). La mediana de supervivencia fue de 72 meses (AR 46,4; HV 68,5 y HH 64,7 meses) y la supervivencia libre de trasplante fue de 26 meses. El éxito técnico y clínico fue del 92,9 y 70,5%, respectivamente. La edad (HR 1,05), el éxito clínico (HR 0,33), el sodio (HR 0,92), la disfunción renal (HR 2,46) y la albúmina (HR 0,35) fueron factores predictivos de supervivencia. El 28,6% desarrolló encefalopatía hepática y un 16,3% presentó disfunción del TIPS. Conclusiones: Los TIPS con prótesis recubiertas dilatadas a 10mm son un tratamiento efectivo y seguro de las complicaciones derivadas de HTP en pacientes cirróticos. La edad, la disfunción renal, el sodio, la albúmina y el éxito clínico son factores independientes predictivos de la supervivencia a largo plazo.(AU)

De-novo nonalcoholic fatty liver disease at 5 years after liver transplantation: prevalence and predictive factors.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors. METHODS: This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method. RESULTS: A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P < 0.001) and de-novo diabetes (OR, 2.79; P = 0.018), were predictive. Significant fibrosis (≥F2) was presented in 58-86%. The mean survival in NAFLD and control group was 166.3 and 173.6 months, respectively (P = 0 0.50). CONCLUSION: De-novo NAFLD at fifth-year post-liver transplantation is frequently and associated with cardiovascular comorbidity. Male sex, obesity, de-novo diabetes and metabolic syndrome were factors associated with de-novo NAFLD. A significant proportion of patients had advanced fibrosis. This group trends toward worse patients' survival.

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. METHODS: This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan-Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. RESULTS: A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/-9.9) and the median MELD was 13.3 (IQR 9.5-16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. CONCLUSIONS: TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.

Utility of Ethyl-Glucuronide for Evaluation of Abstinence in Patients Presenting for Liver Transplantation.

BACKGROUND: Cirrhosis as a result of alcohol-related liver disease is one of the most common indications for liver transplantation (LT) in Spain. Patients presenting for LT should be checked for alcohol abuse in clinical interviews and use of laboratory tests to confirm abstinence. The ethyl-glucuronide (EtG) test is very sensitive and can be positive in urine up to 5 days after consumption. Our main objective is to know the rate of alcohol abstinence by using the urine EtG test in patients evaluated for LT and to assess its correlation with the clinical interviews and laboratory test. METHODS: We conducted a prospective analysis of the results of the EtG in urine of patients evaluated for LT from January 2017 to March 2019 and its correlation with the medical and psychiatric interviews and with the laboratory test. RESULTS: We included 160 patients who were referred to LT evaluation. Among all cases, 84.1% were men, with an average age of 57.8 years. Alcohol-related liver disease was the most frequent cause (64.1%). Urine-EtG was positive in 10 patients (6.2%), 9 of them in patients with ALD and 1 in a patient with hepatitis C virus. The alcohol consumption was recognized by 80% of the patients in the clinical interview. Cases with positive EtG had higher levels of analytical parameters than those with a negative test. CONCLUSIONS: In our series, 6.2% of patients referred for LT evaluation had recently consumed alcohol. The determination of EtG in urine is probably an effective and objective technique in the detection of alcohol consumption to ensure abstinence in the LT candidates.

Immunosuppressive Treatment With mTOR Inhibitors for Malignancies After Liver Transplantation: Long-Term Survival Retrospective Analysis.

BACKGROUND: Immunosuppressive calcineurin inhibitors have been associated with an increased risk of post-transplant malignancies. The mammalian target of rapamycin inhibitors (mTORi) is an alternative immunosuppressive regimen with an antineoplastic effect. The aim of the study was to determine the long-term survival of mTORi-treated recipients with de novo or recurring tumors after liver transplantation (LT). METHODS: This retrospective analysis included mTORi-treated LT recipients between March 2013 and March 2019. We analyzed long-term survival and mTORi indications in an oncology setting in patients with de novo and recurrent malignancies after LT. Overall survival (OS) rate was compared from the Spanish Liver Transplant Registry (SLTR) data using the Kaplan-Meier method. High-risk hepatocellular carcinoma (HCC) was defined as microvascular invasion or satellite lesions as described in the liver explant. RESULTS: A total of 237 patients underwent LT during the study period; 111 patients underwent mTORi-based immunosuppression (48%, cancer was the main indication): 24.5% high-risk HCC; 24.4% HCC recurrence; 14.3% cholangiocarcinoma; and 36.7% de novo malignancies. The 1- and 5-year OS rates after LT in the mTORi group were 83% and 65%, respectively (SLTR group, 85% and 72.6%, respectively); 30.6% patients received mTORi monotherapy, and 38.7% patients had an early switch to mTORi in the first 3 months after oncologic diagnosis. mTORi monotherapy or oncologic treatment strategies had a nonsignificant association with prognosis. The OS rate was higher when the mTORi switch occurred early, 83% and 67%, respectively. CONCLUSIONS: mTORi-based immunosuppression may be a preferred option in patients transplanted with tumors. The OS rate was comparable to data from the SLTR. An mTORi early switch improves OS rate.