High MELD Score Research Articles

Interferon‐free therapy of chronic hepatitis C with direct‐acting antivirals does not change the short‐term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols. 158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000)days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups. IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5years of follow-up.

Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis. data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed. There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation. ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking. No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.

A Review of Paracentesis Performance in Ascites Following Simulation-Based Training

Introduction: Guidelines recommend that a diagnostic paracentesis be performed in all patients with cirrhosis and ascites upon hospital admission. Paracentesis is often performed by internal medicine (IM) residents however few institutions have a formal training program. Delays in paracentesis >12 hours have also been linked to increased patient mortality. Methods: We implemented a simulation-based training (ST) course for IM residents to improve resident confidence and competence in paracentesis. 130 IM residents underwent ST which included precourse reading, small group discussions, and task training. We performed a retrospective review of all patients with ascites admitted in two 12-month periods, before and after ST at 2 academic teaching hospitals. The primary outcome was time from admission to paracentesis. Secondary outcomes included in-hospital mortality, hospital length of stay (LOS), and development of acute kidney injury (AKI). Results: A pre-course survey revealed that most residents had never performed a paracentesis, had little prior training and were not confident in performing paracentesis. A total of 678 charts were reviewed, and a total of 89 paracenteses were performed pre-ST and 65 post-ST. IM residents performed more paracenteses following ST (23.6% vs. 33.9%). The remainder were performed by interventional radiology (IR). Mean time to paracentesis decreased for housestaff (49.1h to 39.9h) and increased for IR (57.5h to 82.2h) after ST. IM residents were more likely to perform paracentesis on patients with higher MELD scores and rate of ICU admission (see Table). There was a statistically significant decrease in development of AKI in the resident cohort (47.6% to 18.2%, p= 0.04) and remained unchanged in the IR-cohort (32.4% to 34.9%). Mean hospital LOS and in-hospital mortality decreased in the resident cohort, while they remained unchanged and increased in the IR-cohort (see Table).Table: Table. Results of Paracentesis Performance Following Simulation-Based TrainingConclusion: Our study shows that after implementation of a simulation-based paracentesis course, IM residents performed a greater proportion of procedures, a decreased time to paracentesis, and had improved patient outcomes. ST improved resident confidence in performing paracentesis and this likely explains the increase in procedures performed by them and in higher acuity patients. Increase in clinical knowledge post-ST regarding paracentesis may explain decreased time to procedure, lower rates of AKI, decreased hospital LOS, and in-hospital mortality seen in the post-intervention period.

PGI6 - How does high meld score increases total expenditure on health system? A micro-costing prospective cohort study

PGI6 - How does high meld score increases total expenditure on health system? A micro-costing prospective cohort study

Heterozygous Hemochromatosis (HH) and Heterozygous Alpha 1 Antitrypsin Deficiency (AAT) as a Cause of Cirrhosis Requiring Liver Transplant

Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations of HFE gene that increases iron absorption in the intestine. It is commonly found in Caucasians. Men have 24 times higher rate of iron overload compared to women. 85-90% of patients with homozygous HFE gene mutation C282Y will be affected. 10% of them will develop clinical symptoms or end organ damage like cirrhosis of liver. Role of heterozygous C282Y or H63D mutations in the development of cirrhosis is still questionable. Alpha 1-Antitrypsin (AAT) deficiency is usually characterized by impaired secretion of α-1 AT from liver cells.This disorder is usually inherited as autosomal co-dominant. AAT deficiency usually is associated with Pi ZZ, Pi SZ, or Pi Null haplotypes and can progress to liver cirrhosis. On the contrary, Pi MZ which is considered the most common heterozygous type often does not lead to liver disease. We are reporting a rare case of both heterozygous HH and AAT deficiency that developed cirrhosis requiring liver transplant. 57 yr old white male who received a liver transplant for end stage liver disease with complications of cirrhosis. Both his father and grandmother had liver disease. Patient was found to have elevated liver enzymes at age 17 during routine physical exam. Lab exam showed elevated iron saturation (83%) and elevated Ferritin (1061) with low α-1 AT. Genetic testing showed HFE heterozygous for C282Y wild type and heterozygous for alpha 1 antitrypsin deficiency MZ phenotype. MRI showed cirrhosis with evidence of portal hypertension. Liver biopsy showed cirrhotic liver with grade 2/4 intra hepatocyte iron deposition. Immunohistochemical stain and PAS- D stains were positive with presence of α-1 AT globule. As Ferritin level continued to rise, patient underwent multiple sessions of phlebotomy. In matter of few years he developed intractable ascites, hepatic encephalopathy, and hepatic hydrothorax. Transjugular intrahepatic portosystemic shunt was not performed due to high MELD score. After thorough workup patient underwent a successful orthotopic liver transplant. Conflicting evidence on the association of the two disorders and on the severity of the condition in patients in whom these disorders coexist have rised from reviewing small numbers of patients. Our case is the first reported case of cirrhosis developed from heterozygous HH C282Y wild type and heterozygous AAT deficiency Pi MZ type which required liver transplant.Figure: Hepatocellular siderosis (Iron stain).Figure: Alpha-1-antitrypsin globules within hepatocytes (Immunostain).Figure: Alpha-1-antitrypsin globules within hepatocytes (PASD stain).

Chronic pancreatitis in patients with liver cirrhosis negatively affects graft survival after liver transplantation

BackgroundLimited data exists concerning the coincidence of chronic pancreatitis (CP) and liver cirrhosis with respect to the patient outcome after liver transplantation (LT). The aim of the study was to identify risk factors for graft loss after liver transplantation and to evaluate the impact of CP on graft survival. MethodsWe analyzed the data of 421 cirrhotic patients who underwent evaluation for primary liver transplantation from January 2007 to January 2014. Diagnosis of CP based on morphologic findings which were graded according to the Cambridge and Manchester classification. (Graft) survival after LT was analyzed by Cox regression analysis. Recipient- and donor-related risk factors for graft loss were evaluated using univariate and multivariate analysis. Results40/421 cirrhotic patients suffered from CP (9.5%). 250/421 (59.4%) patients underwent LT between January 2007 and January 2014. In total, 89 patients died or were in need of a re-transplantation during follow-up until August 2017. Patients with CP (N = 26) were at increased risk for graft loss after LT (hazard ratio = 2.183; 95% confidence interval = 1.232–3.868). CP (P = 0.001), a MELD score ≥24 (P = 0.021), absence of esophageal or gastrical varices (P = 0.018), the age of the donor (P = 0.008) and infections after transplantation (P = 0.030) were independent risk factors for organ loss after transplantation in the multivariate Cox regression analysis. ConclusionPatients with chronic pancreatitis are at increased risk for graft loss after LT. A high MELD score, the absence of esophageal or gastrical varices, an advanced donor age and post-transplant infections negatively affect graft survival, too.

Incidence, predictive factors and impacts of acute kidney injury in cirrhotic patients hospitalized for cellulitis.

Cellulitis is a common infection in patients with cirrhosis but its impact on progression of liver disease has been hardly addressed. This study examines the incidence of acute kidney injury (AKI), predictive factors and its impacts on mortality in cirrhotic patients hospitalized for cellulitis. Retrospective data from cirrhotic patients hospitalized for cellulitis over the period January 2006 to September 2015 were analysed. AKI was defined according to revised criteria of the International Club of Ascites. A total of 101 episodes of cellulitis were examined (70.3% men; mean age 60.6±13.6years). Of patients, 27% met criteria for acute on chronic liver failure (ACLF) (grade 1: 63%; grade 2: 22%; grade 3: 15%). AKI was recorded in 50.5% (type 1: 67%; type 2: 19%; type 3: 14%). AKI was present on admission in 21 of the 51 patients (41%) who developed it. In the remaining 30 patients (59%), AKI appeared during hospitalization and its development was associated with a MELD score >14 (70% vs 30%, P=.024). In-hospital mortality was 10% and all patients who died had AKI. A high MELD score on admission, AKI and ACLF were associated with in-hospital mortality (P<.05). One-month transplant-free survival was 84% (70% vs 98% in patients with and without AKI, P=.001). In cirrhotic patients, cellulitis is a serious infection that often leads to AKI and ACLF. AKI is a strong predictor of mortality in this setting.

Absolute quantification of microparticles by flow cytometry in ascites of patients with decompensated cirrhosis: a cohort study

BackgroundMicroparticles (MPs) are small (<1 μm) cell membrane-derived vesicles that are formed in response to cellular activation or early stages of apoptosis. Increased plasma MP levels have been associated with liver disease severity. Here we investigated the clinical impact of ascites MPs in patients with decompensated liver cirrhosis.MethodsAscites and blood samples of 163 patients with cirrhosis (ascites n = 163, blood n = 31) were collected between February 2011 and December 2012. MPs were obtained from ascites and from blood by two-step ultracentrifugation and quantified by flow cytometry. Quantitative absolute MP levels were correlated with clinical and laboratory baseline parameters as well as patient outcomes. Ascites microparticles were stained with antibodies against CD66b (neutrophils) and CD3 (lymphocytes) in a subgroup of 60 matched patients.ResultsMPs were detected in all ascites and blood samples. Absolute ascites MP levels correlated with blood levels (r = 0.444, p = 0.011). Low ascites MP levels (<488.4 MP/μL) were associated with a poor 30-day survival probability (<488.4 MP/μL 71.1% vs. >488.4 MP/μL 94.7%, log rank p = 0.001) and such patients had a higher relative amount of ascites microparticles derived from neutrophils and lymphocytes. Low levels of ascites MPs, high MELD score and antibiotic treatment were independent risk factors for death within 30 days.ConclusionsAscites MP levels predict short-term survival along with the liver function in patients with decompensated cirrhosis. Further studies which evaluate ascites MPs as disease specific biomarker with a validation cohort and which investigate its underlying mechanisms are needed. Neutrophils and lymphocytes contributed more frequently to the release of microparticles in patients with low ascites levels, possibly indicating an immune activation in this cohort.

SX-Ella Stent Danis Effectively Controls Refractory Variceal Bleed in Patients with Acute-on-Chronic Liver Failure

Almost 10% of bleeding episodes are refractory to combination of vasoactive agent and endotherapy, and are associated with a mortality up to 50%. Severity of liver disease and high portal pressure are mainly responsible for it. TIPS cannot be used in these patients due to high MELD score. We aimed to evaluate the efficacy of self-expandable DE stents for control of refractory variceal bleeds in patients with ACLF. Acute-on-chronic liver failure patients (n=88, mean age 47.3±10.9years) with refractory variceal bleeds received either DE stent (Gr. A, n=35) or continued with repeat endotherapy and vasoactive drug (Gr.B, n=53). Matching by propensity risk score (PRS) was done to avoid selection bias. Competing risk Cox regression analysis was done to identify event-specific, i.e., gastrointestinal bleed-related death. Majority (78.4%) of patients were alcoholic with MELD score of 45.9±20.1. Control of initial bleeding was significantly more in the DE stent group as compared to controls in both pre-match (89 vs. 37%; p<0.001) and PRS-matched cohorts (73 vs. 32%; 0.007). Further, bleed-related death was also significantly lower in DE group as compared to controls in both pre-match (14 vs. 64%; p=0.001) and PRS-matched cohorts (6 vs. 56%; p=0.001). In a multivariate competing risk Cox model, patients who underwent DE stenting had reduced mortality in both pre-match (p=0.04, HR 0.36, 95% CI 0.13-0.96) and PRS-matched cohorts (p<0.001, HR 0.21, 95% CI 0.08-0.51). Self-expandable DE stents are very effective in control of refractory variceal bleeding and reduced mortality in patients with severe liver failure.

The impact of infections on delisting patients from the liver transplantation waiting list.

Approximately 20% of the patients listed for liver transplantation die before transplantation can be accomplished. Understanding risk factors for waiting list mortality may help to improve survival and organ allocation. Infections are very common in patients with cirrhosis and are associated with significant morbidity and mortality. This study analysed the frequency and characteristics of infections in patients awaiting liver transplantation, identified risk factors for withdrawal from the waiting list and evaluated the impact of infections on the clinical outcome. A retrospective analysis of consecutive patients listed for liver transplantation in Rotterdam, the Netherlands from 2007 to 2014 was conducted. Infections occurred in 144 of 327 studied patients (44%). In this cohort, 23.4% of the patients on the liver transplantation waiting list were delisted or died before transplantation. Patients with an infection were 5.2 times more likely to become delisted than noninfected patients. In the 30days after the first infection, patients were 33.8 times more likely to become delisted compared to noninfected patients. High age, high MELD score, refractory ascites and inappropriate antibiotic therapy were independent predictors for delisting due to infection. Infections occur frequently in patients on the liver transplantation waiting list. Emphasis on appropriate and timely antimicrobial therapy is required.

Hospital mortality in cirrhotic patients at a tertiary care center.

Cirrhosis of the liver is known for its high risk of mortality associated with episodes of acute decompensation. There is an even greater risk in patients that present with acute-on-chronic liver failure. The identification of patients at higher risk for adverse outcomes can aid in making the clinical decisions that will improve the prognosis for these patients. To determine in-hospital mortality and evaluate the epidemiologic and clinical characteristics of patients with cirrhosis of the liver seen at a tertiary referral hospital. A descriptive, observational, cohort study was conducted on adult patients with cirrhosis of the liver, admitted to a tertiary care center in Bucaramanga, Colombia, within the time frame of March 1, 2015 and February 29, 2016. Eighty-one patients with a mean age of 62 years were included in the study. The main etiology of the cirrhosis was alcoholic (59.3%). In-hospital mortality was 23.5% and the most frequent cause of death was septic shock (68.4%), followed by hypovolemic shock (10.5%). A MELD score≥18, a leukocyte count>12,000/ul, and albumin levels below<2.5g/dl were independent factors related to hospital mortality. In-hospital mortality in cirrhotic patients is high. Sepsis and bleeding are the 2 events leading to acute-on-chronic liver failure and death. A high MELD score, elevated leukocyte count, and low level of albumin are related to poor outcome during hospitalization. Adjusted prevention-centered public health measures and early and opportune diagnosis of this disease are needed to prevent the development of complications and to improve outcome in cirrhotic patients.

Hospital mortality in cirrhotic patients at a tertiary care center

IntroductionCirrhosis of the liver is known for its high risk of mortality associated with episodes of acute decompensation. There is an even greater risk in patients that present with acute-on-chronic liver failure. The identification of patients at higher risk for adverse outcomes can aid in making the clinical decisions that will improve the prognosis for these patients. AimsTo determine in-hospital mortality and evaluate the epidemiologic and clinical characteristics of patients with cirrhosis of the liver seen at a tertiary referral hospital. MethodologyA descriptive, observational, cohort study was conducted on adult patients with cirrhosis of the liver, admitted to a tertiary care center in Bucaramanga, Colombia, within the time frame of March 1, 2015 and February 29, 2016. ResultsEighty-one patients with a mean age of 62 years were included in the study. The main etiology of the cirrhosis was alcoholic (59.3%). In-hospital mortality was 23.5% and the most frequent cause of death was septic shock (68.4%), followed by hypovolemic shock (10.5%). A MELD score≥18, a leukocyte count>12,000/ul, and albumin levels below<2.5g/dl were independent factors related to hospital mortality. ConclusionsIn-hospital mortality in cirrhotic patients is high. Sepsis and bleeding are the 2 events leading to acute-on-chronic liver failure and death. A high MELD score, elevated leukocyte count, and low level of albumin are related to poor outcome during hospitalization. Adjusted prevention-centered public health measures and early and opportune diagnosis of this disease are needed to prevent the development of complications and to improve outcome in cirrhotic patients.

Bacterial meningitis complicating the course of liver cirrhosis.

Patients with cirrhosis and bacterial meningitis were enrolled. Cirrhosis was defined by liver histology or clinical, laboratory, and ultrasonographic and endoscopic findings. Bacterial meningitis was defined by cerebro-spinal fluid pleocytosis (>10/mcl) and characteristic clinical presentation. Fisher exact test and Wilcoxon rank-sum test were employed as appropriate for statistical analysis. Forty-four patients with bacterial meningitis and cirrhosis were enrolled in the study. Sex ratio (male:female) was 1.4:1 and median (IQR) age was 64 (55-72) years. Cirrhosis was viral in 40 patients. At admission, median (IQR) MELD score was 12 (9-14), and median (IQR) Child-Pugh score was 8 (6-10). Other conditions associated with immunodepression were present in 22 (50%) cases. Streptococcus pneumoniae and Listeria monocytogenes were the agents more frequently identified. An extra-meningeal focus of infection was identified in 17 (39%) cases. Main symptoms at admission were fever, nuchal rigidity, and an obtunded or comatose status, and at least 2 of these were reported in 37 (84%) episodes. Cerebro-spinal fluid showed high cells, low CSF/serum glucose ratio, and elevated protein. Seventeen patients (39%) died and 8 (18%) reported sequelae. High MELD and Child-Pugh scores were related to the mortality risk (p<0.001). The findings of blood and cerebro-spinal fluid analysis were not predictive of outcome. Bacterial meningitis should be considered in cirrhotics presenting with fever and altered conscience status. MELD and Child-Pugh scores predicted prognosis.

African Americans have a lower prevalence of portal vein thrombosis at the time of liver transplantation

BackgroundPerioperative vascular thrombotic events in patients undergoing liver transplantation (LT) are associated with significant morbidity and mortality. MethodsIn this retrospective UNOS database analysis, we evaluated the prevalence of portal vein thrombosis (PVT) and factors contributing to PVT development in different ethnic groups. ResultsOf the 47 953 LT performed between 2002 and 2015, we identified 3642 cases of PVT. African Americans (AA) had a significantly lower prevalence of PVT compared to other ethnic groups (p = 0.0001). Multivariable regression analysis confirmed that AA were less likely than other ethnicities to have PVT (OR = 0.6). AA cohort was more likely to have infectious or autoimmune causes of liver failure (OR = 1.6, 1.7 respectively) as well as higher creatinine and INR compared to other groups (OR = 1.6, 1.3 respectively). AA's were less likely to have encephalopathy, ascites, or variceal bleeding, which might indicate lower portal pressures. AA's were listed for LT later than other ethnicities and had both a lower functional status and higher MELD score at the time of registration. DiscussionAA's had a significantly lower prevalence of preoperative PVT despite having a greater number of factors predisposing to thrombosis. This predisposition should be considered before instituting perioperative antithrombotic therapy.

Cost of achieving equivalent outcomes in sicker patients after liver transplant

Objective: Determinants of cost after liver transplant (OLT) are unknown. We aimed to characterize the variability in cost after uncomplicated OLT and determine impact on graft and overall survival. Methods: Using a linkage between the University Health Systems Consortium and Scientific Registry of Transplant Recipients databases, we identified 12,245 patients who underwent OLT between 2011 and 2014. Patients who met criteria for uncomplicated OLT, defined as length of stay (LOS) <14 days with discharge to home, were selected (n=5,763). Patients were grouped into tertiles (low, medium, high) according to cost of perioperative stay. Results: Patients undergoing uncomplicated OLT were of similar age, gender, insurance status, and etiology of liver disease across all three groups. High cost patients were more likely on hemodialysis preoperatively, had higher severity of illness, and had higher MELD score (all p < 0.01). High cost patients required increased utilization of resources including lab tests, blood transfusions, and opioids (all p < 0.01). Despite higher burden of disease necessitating increased resource utilization, high cost OLT patients with an uncomplicated perioperative course were shown to have identical 2-year graft and overall survival compared to lower cost patients (p=0.66 and p=0.94, respectively). Conclusion: Improved perioperative outcomes in OLT patients with higher severity of illness and disease burden will require increased cost and resource utilization; however doing so provides these patients with equivalent long term survival. These findings support a recipient risk-based bundled reimbursement for liver transplantation.

Hepatocellular carcinoma in Danish patients: a single Copenhagen center experience

Objective: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival.Methods: All patients diagnosed with HCC from January 2008 to December 2014 were retrospectively enrolled in this study. Overall survival was estimated by using the Kaplan–Meier method. A multivariate Cox regression analysis was performed to identify predictive factors for survival.Results: Sixty-seven patients were diagnosed with HCC (incidence rate 3.55/100,000 people/year). Ninety-three percent had underlying cirrhosis. Alcohol-related liver disease and chronic viral hepatitis B or C were responsible for 55 and 31% of cases, respectively. Median survival was 81 days and 1-month, 3-months and 1-year cumulative survival rates were 74, 40 and 17%, respectively. We identified the presence of portal vein thrombosis, high Child–Pugh score, high MELD score and high AST as independent negative prognostic factors for survival. Survival was poorer in patients seen for the first time when the diagnosis of HCC was made than in patients followed in the outpatient clinic (p = .06) indicating a substantial delay in diagnosis.Conclusions: Survival was poor in this cohort of patients, almost exclusively caused by delay in diagnosis and admittance to hospital. An increased general information about HCC and the possibilities of therapy seems warranted.

High MELD score and extended operating time predict prolonged initial ICU stay after liver transplantation and influence the outcome.

BackgroundThe aim of the present study is to determine the incidence of a prolonged (>3 days) initial ICU-stay after liver transplantation (LT) and to identify risk factors for it.Patients and methodsWe retrospectively analyzed data of adult recipients who underwent deceased donor first-LT at the University Hospital Essen between 11/2003 and 07/2012 and showed a primary graft function.ResultsOf the 374 recipients, 225 (60.16%) had prolonged ICU-stay. On univariate analysis, donor INR, high doses of vasopressors, “rescue-offer” grafts, being hospitalized at transplant, high urgency cases, labMELD, alcoholic cirrhosis, being on renal dialysis and length of surgery were associated with prolonged ICU-stay. After multivariate analysis, only the labMELD and the operation’s length were independently correlated with prolonged ICU-stay. Cut-off values for these variables were 19 and 293.5 min, respectively. Hospital stay was longer for patients with a prolonged initial ICU-stay (p<0.001). Survival rates differed significantly between the two groups at 3 months, 1-year and 5-years after LT (p<0.001).ConclusionsLabMELD and duration of LT were identified as independent predictors for prolonged ICU-stay after LT. Identification of recipients in need of longer ICU-stay could contribute to a more evidenced-based and cost-effective use of ICU facilities in transplant centers.

Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates

Isoniazid daily for 9months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited. Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1month after treatment completion and at routine follow-up visits with their transplant providers. Eleven patients were men, and the median age was 60years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40months following transplantation. Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

Adult Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure in High-Model for End-Stage Liver Disease Score Patients.

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.

MicroRNA-155 is upregulated in ascites in patients with spontaneous bacterial peritonitis

MircoRNA’s (miR) have been recognised as important modulators of gene expression and potential biomarkers. However, they have been rarely investigated in bio fluids apart from blood. We investigated the association of miR-125b and miR-155 with complications of cirrhosis. Ascites was prospectively collected from patients with cirrhosis undergoing paracentesis at our department. miR’s were determined in the supernatant using qPCR and normalized by SV-40. Clinical parameters were assessed at paracentesis and during follow-up. 76 specimens from 72 patients were analysed. MiR’s were not associated to age, sex or aetiology of cirrhosis. MiR-125b levels differed between patients with low and high MELD score, and miR-125b levels showed an inverse correlation to serum creatinine (r2 = −0.23; p = 0.05). MiR-155 was elevated in patients with spontaneous bacterial peritonitis (SBP) (n = 10; p = 0.04). MiR-155 levels differed between patients with and without 30-day survival (p = 0.02). No association of ascites levels of investigated miR’s to size of varices, episodes of gastrointestinal bleeding or hepatorenal syndrome was observed. While miR-125b levels in ascites seem to be associated with liver and renal dysfunction, miR-155 might be implicated in local immune response in SBP.