Management of Biliary Complications in Liver Transplant Recipients.

Biliary complications are often referred to as the Achilles' heel of liver transplantation (LT). The most common of these complications include strictures, and leaks. Prompt diagnosis and management is key for preservation of the transplanted organ. Unfortunately, a number of factors can lead to delays in diagnosis and make adequate treatment a challenge. Innovations in advanced endoscopic techniques have increased non-surgical options for these complications and in many cases is the preferred approach.

Hepatobiliary phenotype of individuals with chronic intestinal disorders.

Despite the known functional relationship between the gut and the liver, the clinical consequences of this circuit remain unclear. We assessed the hepatobiliary phenotype of cohorts with celiac disease (CeD), Crohn´s disease (CD) and ulcerative colitis (UC). Baseline liver function tests and the frequency of hepatobiliary diseases were analyzed in 2377 CeD, 1738 CD, 3684 UC subjects and 488,941 controls from the population-based UK Biobank cohort. In this cohort study associations were adjusted for age, sex, BMI, diabetes, and alcohol consumption. Compared to controls, cohorts with CeD, but not CD/UC displayed higher AST/ALT values. Subjects with CD/UC but not CeD had increased GGT levels. Elevated ALP and cholelithiasis were significantly more common in all intestinal disorders. Non-alcoholic steatohepatitis and hepatocellular carcinoma (HCC) were enriched in CeD and CD (NASH: taOR = 4.9 [2.2-11.0] in CeD, aOR = 4.2 [1.7-10.3] in CD, HCC: aOR = 4.8 [1.8-13.0] in CeD, aOR = 5.9 [2.2-16.1] in CD), while cholangitis was more common in the CD/UC cohorts (aOR = 11.7 [9.1-15.0] in UC, aOR = 3.5 [1.8-6.8] in CD). Chronic hepatitis, autoimmune hepatitis (AIH) and cirrhosis were more prevalent in all intestinal disorders. In UC/CD, a history of intestinal surgery was associated with elevated liver enzymes and increased occurrence of gallstones (UC: aOR = 2.9 [2.1-4.1], CD: 1.7 [1.2-2.3]). Our data demonstrate that different intestinal disorders predispose to distinct hepatobiliary phenotypes. An increased occurrence of liver cirrhosis, NASH, AIH and HCC and the impact of surgery warrant further exploration.

Incidence and computed tomography findings of lenvatinib-induced pancreatobiliary inflammation: A single-center, retrospective study.

ABSTRACT: In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ±â€Šstandard deviation, 69.8 ±â€Š9.4 years, range: 39-84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016-September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.

Epidemiology of pyogenic liver abscesses in Germany: Analysis of incidence, risk factors and mortality rate based on routine data from statutory health insurance.

BACKGROUND: Pyogenic liver abscesses (PLAs) represent potentially life-threatening abdominal conditions that require immediate diagnosis and therapy. European and American incidence figures vary between one and 15 per 100,000 per year. Structured epidemiological data for European countries are not available. OBJECTIVE: To systematically characterize the epidemiology and clinical outcome of PLA in Germany. METHODS: In representative statutory health insurance data from four million people in 2013-2019, the prevalence and incidence with clinical coding of International Statistical Classification of Diseases and Related Health Problems (ICD)-10 code K75.0 were selected (n = 1118). Furthermore, demographics, relevant comorbidities, hospitalizations, mortality and complications were determined within one year. RESULTS: The incidence of PLA was approximately seven per 100,000. The average age at diagnosis was 66 years; 65% were male. Of these, biliary disease was documented in over 60% and infectious intestinal diseases were found in 21% within the same or previous calendar year. PLA patients had high comorbidity indices. Liver transplant status, malignancies of the liver and biliary system, liver cirrhosis and pancreatitis were strongly associated. Intensive care was documented in 27% of PLA cases. Nine percent died within 12 months, most with an underlying malignant disease. CONCLUSION: Pyogenic liver abscess is a rare disease with high morbidity. Predisposing and risk factors include intestinal and biliary diseases as well as hepatic malignancies. Further research should focus on PLA therapy within prospective surveys and controlled clinical trials.

Biliary and duodenal complications after « en bloc¼ liver-small bowel transplantation in children. A single center cohort study.

BACKGROUND: The technique of « en bloc¼ liver and small bowel transplantation (L-BT) spares a biliary anastomosis, but does not protect against biliary complications. We analyze biliary and duodenal complications (BDC) in our pediatric series. METHODS: Between 1994 and 2020, 54 L-BT were performed in 53 children. The procurement technique included in situ vascular dissection and pancreatic reduction to the head until 2009 (group A). Thereafter, the whole pancreas was recovered (group B). RESULTS: Nine BDCs occurred in 8/53 (15%) patients (7 in group A and 1 in group B): leak of the donor's duodenal stump (2), stenosis of the extra-pancreatic bile duct (5), and intra-pancreatic bile duct stenosis (2). Median delay for diagnosis of stricture was 8 months (4-168). Interventional radiology was successful in one child only, the others required reoperations. Two patients died, of biliary cirrhosis or cholangitis, 15-month and 12-year post-L-BT. One was listed and liver re-transplanted 13 years post-L-BT. At last follow-up, two patients only had normal liver tests and ultrasound. CONCLUSION: BDC after L-BT can cause severe morbidities. Pancreatic reduction might increase this risk. Early surgical complications or chronic pancreatic rejection might be co-factors. Early diagnosis and treatment are key to the long-term prognosis.

Risk factors and impact of early anastomotic biliary complications after liver transplantation: UK registry analysis.

BACKGROUND: Biliary leaks and anastomotic strictures are common early anastomotic biliary complications (EABCs) following liver transplantation. However, there are no large multicentre studies investigating their clinical impact or risk factors. This study aimed to define the incidence, risk factors and impact of EABC. METHODS: The NHS registry on adult liver transplantation between 2006 and 2017 was reviewed retrospectively. Adjusted regression models were used to assess predictors of EABC, and their impact on outcomes. RESULTS: Analyses included 8304 liver transplant recipients. Patients with EABC (9·6 per cent) had prolonged hospitalization (23 versus 15 days; P < 0·001) and increased chance for readmission within the first year (56 versus 32 per cent; P < 0·001). Patients with EABC had decreased estimated 5-year graft survival of 75·1 versus 84·5 per cent in those without EABC, and decreased 5-year patient survival of 76·9 versus 83·3 per cent; both P < 0.001. Adjusted Cox regression revealed that EABCs have a significant and independent impact on graft survival (leak hazard ratio (HR) 1·344, P = 0·015; stricture HR 1·513, P = 0·002; leak plus stricture HR 1·526, P = 0·036) and patient survival (leak HR 1·215, P = 0·136, stricture HR 1·526, P = 0·001; leak plus stricture HR 1·509; P = 0·043). On adjusted logistic regression, risk factors for EABC included donation after circulatory death grafts, graft aberrant arterial anatomy, biliary anastomosis type, vascular anastomosis time and recipient model of end-stage liver disease. CONCLUSION: EABCs prolong hospital stay, increase readmission rates and are independent risk factors for graft loss and increased mortality. This study has identified factors that increase the likelihood of EABC occurrence; research into interventions to prevent EABCs in these at-risk groups is vital to improve liver transplantation outcomes.

T-tube or no T-tube for biliary tract reconstruction in orthotopic liver transplantation: an updated systematic review and meta-analysis.

Objectives: Biliary tract reconstruction with or without T-tube is commonly used in orthotopic liver transplantation (OLT). However, the efficacy and safety of T-tube usage remain controversial. This meta-analysis was conducted to assess the latest evidence of clinical outcomes.Methods: Embase, Cochrane Library, PubMed, and Web of Science were systematically searched from inception to 20 January 2021 for eligible studies. The analyses were performed using Review Manager and Stata.Results: A total of 24 trials involving 3320 participants were included in the meta-analysis. Compared with the no T-tube group, there was a higher incidence of overall biliary complications (OR:1.54; 95%CI, 1.06-2.24; P = 0.02), bile leaks (OR:2.34; 95%CI,1.57-3.48; P < 0.0001), cholangitis (OR:2.78; 95%CI,1.19-6.51; P = 0.002), and longer cold ischemia time (MD:22.27; 95%CI,0.80-43.74; P = 0.04) in the T-tube group. Furthermore, the no T-tube group had significantly higher odds of biliary strictures than the T-tube group (OR:0.60; 95%CI, 0.47-0.78; P = 0.0001).Conclusion: T-tube is still not routinely recommended, but is a good choice for OLT patients at high risk of biliary strictures. Notably, the higher rate of biliary complications in the T-tube group did not translate into an increase in endoscopic or re-operative interventions.

Asociación entre los factores socioeconómicos y las complicaciones postoperatorias de la colecistectomía / Association between socioeconomic factors and postoperative complications of cholecystectomy

El objetivo de este artículo es determinar si los factores socioeconómicos inciden en las complicaciones posoperatorias de la colecistectomía. Para ello, se definió realizar un estudio de tipo observacional, analítico y enfoque cuantitativo, en 100 pacientes en los que se les realizó colecistectomía. Se aplicó un modelo de regresión logística en el que se incorporaron como variables, factores de riesgo, características socioeconómicas, junto con una variable de control. Se aplicaron tres modelos con variables dependientes alternativas que están delimitadas por el tipo de complicación posoperatoria registrado. Los resultados encontrados mostraron que las mujeres manifiestan un mayor riesgo de presentar complicaciones posteriores a la colecistectomía, igual ocurre en los pacientes de mayor edad. Asimismo el riesgo es mucho menor en las personas con niveles de educación superior y en los pacientes en los que se realizó colecistectomía laparoscópica, alcanzando solo un 5% de riesgo de presentar complicaciones. Las complicaciones posoperatorias luego de la colecistectomía se minimizan al emplear la técnica laparoscópica y los factores socioeconómicos incidirían en el riesgo de padecer complicaciones posoperatorias luego de dicha cirugía, lo que la convierte a la colecistectomía laparoscópica en una operación segura y con muchos otros beneficios y ventajas sobre la cirugía tradicional o convencional.

The article ́s goal isto determine if socioeconomic factors influence the postoperative complications of cholecystectomy. For this, the observational study was defined, analytical and quantitative study was conducted in 100 patients who underwent cholecystectomy. A logistic regression model was applied in which risk factors, socioeconomic characteristics, along with a control variable, were incorporated as variables. Three models were run with alternative dependent variables that are delimited by the type of postoperative complication recorded. The results found showed that women show a higher risk of presenting complications after cholecystectomy, the same occurs in older patients. Likewise, the risk is much lower in people with higher education levels and in patients who underwent laparoscopic cholecystectomy, they only have a 5% risk of presenting complications. Postoperative complications after cholecystectomy are minimized by using the laparoscopic technique and socioeconomic factors would influence the risk of suffering postoperative complications after said surgery, which makes laparoscopic cholecystectomy a safe operation with many other benefits and advantages over traditional or conventional surgery.

Obstructive jaundice: Studies on predictors of biliary infection and microbiological analysis in an HIV setting.

BACKGROUND: Early diagnosis of biliary infection is critical for timely antimicrobial therapy and biliary drainage. HIV infection may influence the spectrum and severity of biliary infection in an environment with a high HIV prevalence. Charcot's triad has low sensitivity and higher specificity for biliary infection, and more sensitive markers are required. OBJECTIVES: To investigate possible predictors of biliary infection (bacteriobilia) and identify the microbiological spectrum in patients presenting with biliary obstruction to a tertiary institute in an environment with a high prevalence of HIV. METHODS: Bile was assessed for infection at endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography and surgery, and the roles of clinical/haematological factors, C-reactive protein (CRP) and procalcitonin (PCT) in determining biliary infection were evaluated. RESULTS: One hundred and six patients with obstructive jaundice had a mean age of 52 years (range 21 - 58); most were female (74%), and 36 (34%) were infected with HIV, with a mean CD4 count of 495 cells/µL. Choledocholithiasis (53%), biliary strictures (21%) and head of pancreas tumour (8%) were the main aetiopathologies. Bile was obtained for microbial culture from 104 patients (98%), and 56 (54%) were infected. Gram-negative bacteria were most frequent (58%), and 2 HIV-infected patients had fungal infections (Candida albicans and Aspergillus fumigatus). Screening for endoscopy-associated infections revealed Pseudomonas aeruginosa. PCT was a poor predictor of bacterial infection, whereas CRP was a fair predictor. CONCLUSIONS: The majority of bacteria cultured were sensitive to ciprofloxacin or amoxicillin-clavulanate. Duodenoscopes were a potential source of Pseudomonas infection.

The real incidence of biliary tract complications after adult liver transplantation: the role of the prospective routine use of cholangiography during post-transplant follow-up.

Biliary tract complications (BTCs) still burden liver transplantation (LT). The wide reporting variability highlights the absence of systematic screening. From 2000 to 2009, simultaneous liver biopsy and direct biliary visualization were prospectively performed in 242 recipients at 3 and 6 months (n = 212, 87.6%) or earlier when indicated (n = 30, 12.4%). Median follow-up was 148 (107-182) months. Seven patients (2.9%) experienced postprocedural morbidity. BTCs were initially diagnosed in 76 (31.4%) patients; 32 (42.1%) had neither clinical nor biological abnormalities. Acute cellular rejection (ACR) was present in 27 (11.2%) patients and in 6 (22.2%) BTC patients. Nine (3.7%) patients with normal initial cholangiography developed BTCs after 60 (30-135) months post-LT. BTCs directly lead to 7 (2.9%) re-transplantations and 14 (5.8%) deaths resulting in 18 (7.4%) allograft losses. Bile duct proliferation at 12-month biopsy proved an independent risk factor for graft loss (P = 0.005). Systematic biliary tract and allograft evaluation allows the incidence and extent of biliary lesions to be documented more precisely and to avoid erroneous treatment of ACR. The combination 'abnormal biliary tract-canalicular proliferation' is an indicator of worse graft outcome. BTCs are responsible for important delayed allograft and patient losses. These results underline the importance of life-long follow-up and appropriate timing for re-transplantation.

Costs Associated With Early Vascular and Biliary Complications in Liver-Transplanted Patients in a Hospital in Antioquia, Colombia 2019: A Case Series.

OBJECTIVES: Vascular and biliary complications associated with liver transplants involve high morbidity and mortality as well as cost overrun for health systems. Efforts to prioritize their prevention require not only clinical information but also information on costs that reflect the economic burden on health systems. The objective of this study was to describe cost overrun incurred from early vascular and biliary complications after liver transplant. METHODS: This cases series included liver transplant patients treated at the San Vicente Foundation University Hospital, Rionegro, Antioquia, from January 1, 2013, to December 31, 2018. All liver transplant patients treated during the above period were included; the absence of clinical records on the variables of interest was considered the exclusion criterion. A probabilistic analysis of patient cost was performed. Monte Carlo simulations as well as a 1-way sensitivity analysis per transplant cost component were performed. RESULTS: Records from 154 patients were assessed. The average patient age was 56.9 (SD 10.9) years; 42.9% of patients were women. Of all, 36.4% patients were classified as Child C, and the average Model for End-Stage Liver Disease score was 19.6. The average cost for patients without complications was $27 834.82, whereas that for patients with early vascular complications was $36 747.83 and for those with early biliary complications was $38 523.74. CONCLUSION: Early vascular and biliary complications after liver transplant increase healthcare costs, with the increase being significant in patients with biliary complications.

Nonanastomotic Biliary Strictures After Liver Transplantation.

Biliary strictures constitute a major source of morbidity and mortality following liver transplantation (LT). However, studies on the impact of nonanastomotic biliary strictures (NABS) on grafts after LT are limited. 649 patients who underwent LT between January 2013 and June 2017 at our center were retrospectively analyzed and 2.6% (n = 17) of the recipients developed NABS following LT. There were no differences between recipients with and without NABS in indication of LT, graft ischemia time, and type of biliary anastomosis. The incidence of post-LT hepatic artery thrombosis (HAT) (odds ratio [OR]: 15.75, P < .001) and the use of livers from donation after cardiac death (DCD) donors (OR: 8.292, P = .004) were identified as independent significant predictors of NABS by multivariate analysis. Graft survival in those with NABS was significantly worse than in patients without NABS (1-, 3-, and 5-years survival: 64.7%, 57.5%, 0%, vs. 89.8%, 84.0%, 76.4%, P < .001). In conclusion, while the incidence of NABS in our study was relatively low compared to previous reports, NABS was still found to be associated with poor graft survival. Special attention should be paid to NABS occurrence in grafts that develop HAT as well as those from DCD donors.

Antenatally detected liver and biliary pathology.

Liver and biliary pathology in the neonate are rare and include a broad range of structural, neoplastic, infectious, genetic, and metabolic diseases. While most conditions present postnatally, antenatal detection is increasing given recent advances in antenatal imaging capabilities. In certain structural or obstructive liver diseases, antenatal detection now proves essential to help guide treatment and prevent morbidity. We review the epidemiology, pathophysiology, common antenatal diagnostic findings, and recommendations for surgical liver and biliary pathology in the neonate.

Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors.

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

Endoscopic treatment of biliary complications after liver transplantation.

BACKGROUND: biliary complications are an important cause of morbidity and mortality after liver transplantation. Endoscopic retrograde cholangiopancreatography (ERCP) is a therapeutic option, which is less invasive than surgical management. MATERIALS AND METHODS: the endoscopic management with ERCP of patients with biliary complications after liver transplantation in the Complexo Hospitalario Universitario de A Coruña between 2012 and 2018 was reviewed. RESULTS: there were 232 liver transplant recipients and biliary complications occurred in 70 (30.1 %) patients. Anastomotic strictures, most of them choledocho-choledochal, constituted the most frequent complication in 43 (61.4 %) patients. Biliary leak occurred in 16 (22.9 %) patients, non-anastomotic strictures in six (8.6 %) and choledocholithiasis in five (7.1 %). ERCP was performed in 39/43 patients with anastomotic strictures, achieving clinical success in 36 (92.3 %). All patients with a biliary leak were treated with CPRE, with a clinical resolution in 10/16 (62.5 %). ERCP was successful in 3/5 patients (60 %) with bile duct stones. In non-anastomotic strictures, ERCP was not effective in any case. Regarding complications, five (7.7 %) patients presented mild-moderate bleeding after biliary sphincterotomy. CONCLUSION: in our study, ERCP is useful in most biliary anastomotic strictures, early biliary leaks and choledocholithiasis after liver transplantation. The rate of ERCP complications in these patients was low and none were lethal.

Risk of biliary tract disease in living liver donors: A population-based cohort study.

BACKGROUND & AIMS: Whether living liver donors have a higher risk of biliary tract disease compared with non-donors remains unknown. METHODS: Data were collected from the Taiwan Longitudinal Health Insurance Database for the 2003-2011 period. The study cohort comprised 1,446 patients aged ≥ 18 years who had served as living liver donors. The primary outcome was the incidence of biliary tract disease. Cox proportional hazards modeling was used to determine the hazard ratios. RESULTS: The incidence density rate of biliary tract disease was 13.9-fold higher in the liver donor (LD) cohort than in the non-LD cohort (10.2 vs. 0.71 per 1,000 person-years), with an adjusted hazard ratio (HR) of 14.2 (95% confidence interval [CI] = 7.73-26.1). Stratified by comorbidity, the relative risk of biliary tract disease was higher in the LD cohort than in the non-LD cohort for both patients with or without comorbidity. The incidence density rate of biliary tract disease was significantly higher in the first 3 years (13.5 per 1,000 person-years in the LD cohort). The highest adjusted HR of biliary tract disease for LD patients compared with the non-LD cohort was 22.4 (95% CI = 10.8-46.1) in the follow-up ≤ 3 years. CONCLUSION: Living liver donors had a higher risk of biliary tract disease compared with non-donors.

Aeromonas dhakensis is not a rare cause of Aeromonas bacteremia in Hiroshima, Japan.

Aeromonas dhakensis, a newly recognized species, is often misidentified as A. hydrophila, A. veronii, or A. caviae by commercial phenotypic tests. Limited data about A. dhakensis are available in Japan. We retrospectively analyzed the patients with monomicrobial Aeromonas bacteremia at Hiroshima University Hospital from January 2011 to December 2017, and species re-identification was conducted using rpoD and gyrB gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Of the 19 strains from blood isolates, A. caviae (n = 9, 47.4%), A. dhakensis (n = 4, 21.1%), A. hydrophila (n = 3, 15.8%), and A. veronii (n = 3, 15.8%) were re-identified. A. dhakensis was phenotypically misidentified as A. hydrophila (n = 3, 75%) or A. sobria (n = 1, 25%). A. dhakensis was also misidentified as A. caviae (n = 2, 50%), A. hydrophila (n = 1, 25%), and A. jandaei (n = 1, 25%) in MALDI-TOF MS system. Malignancies (n = 12, 63.2%) and liver cirrhosis (n = 7, 36.8%) were common comorbidities. Biliary tract infection was the most frequent source of Aeromonas bacteremia (n = 11, 57.9%). The major source of A. dhakensis bacteremia was also biliary tract infection (n = 3, 75%), and the 14-day infection-related mortality of A. dhakensis was 25%. A. dhakensis isolates showed similar clinical characteristics, antimicrobial susceptibility, and mortality with those of other Aeromonas species isolates. This study demonstrated that A. dhakensis is not a rare cause of Aeromonas bacteremia, but is often misidentified as A. hydrophila in Hiroshima, Japan. Further studies should be conducted to identify the geographical distribution and clinical impact of A. dhakensis in Japan.