Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.

MELD-GRAIL-Na: Glomerular Filtration Rate and Mortality on Liver-Transplant Waiting List.

BACKGROUND AND AIMS: Among patients with cirrhosis awaiting liver transplantation, prediction of wait-list (WL) mortality is adjudicated by the Model for End Stage Liver Disease-Sodium (MELD-Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. APPROACH AND RESULTS: We developed (2014) and validated (2015) a model incorporating eGFR using national data (n = 17,095) to predict WL mortality. Glomerular filtration rate (GFR) was estimated using the GFR assessment in liver disease (GRAIL) developed among patients with cirrhosis. Multivariate Cox proportional hazard analysis models were used to compare the predicted 90-day WL mortality between MELD-GRAIL-Na (re-estimated bilirubin, international normalized ratio [INR], sodium, and GRAIL) versus MELD-Na. Within 3 months, 27.8% were transplanted, 4.3% died on the WL, and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (hazard ratio [HR] 0.382, 95% confidence interval [CI] 0.344-0.424) and the re-estimated model MELD-GRAIL-Na (HR 1.212, 95% CI 1.199-1.224) were significant predictors of mortality or being delisted on the WL within 3 months. MELD-GRAIL-Na was a better predictor of observed mortality at highest deciles of disease severity (≥ 27-40). For a score of 32 or higher (observed mortality 0.68), predicted mortality was 0.67 (MELD-GRAIL-Na) and 0.51 (MELD-Na). For women, a score of 32 or higher (observed mortality 0.67), the predicted mortality was 0.69 (MELD-GRAIL-Na) and 0.55 (MELD-Na). In 2015, use of MELD-GRAIL-Na as compared with MELD-Na resulted in reclassification of 16.7% (n = 672) of patients on the WL. CONCLUSION: Incorporation of eGFR likely captures true GFR better than SCr, especially among women. Incorporation of MELD-GRAIL-Na instead of MELD-Na may affect outcomes for 12%-17% awaiting transplant and affect organ allocation.

Model for End-Stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease.

BACKGROUND AND AIMS: Compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased LA clearance. We hypothesized that a parsimonious model consisting of Model for End-Stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. APPROACH AND RESULTS: We examined all patients with CLD in two large and diverse health care systems in Texas (North Texas [NTX] and Central Texas [CTX]) between 2010 and 2015. We developed (n = 3,588) and validated (n = 1,804) a model containing MELD and LA measured at the time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 726). MELD-LA was an excellent predictor of inpatient mortality in development (concordance statistic [C-statistic] = 0.81, 95% confidence interval [CI] 0.79-0.82) and both validation cohorts (CTX cohort, C-statistic = 0.85, 95% CI 0.78-0.87; multicenter cohort C-statistic = 0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (C-statistic = 0.84, 95% CI 0.81-0.86) or sepsis (C-statistic = 0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality rates were 11.2% (LA = 1 mmol/L), 19.4% (LA = 3 mmol/L), 34.3% (LA = 5 mmol/L), and >50% (LA > 8 mmol/L). A linear increase (P < 0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of patients compared to MELD alone. CONCLUSIONS: MELD-LA (bswh.md/meldla) is an early and objective predictor of inpatient mortality and may serve as a model for risk assessment and guide therapeutic options.

Incidence and Risk Factors Associated With 30-Day Readmission for Alcoholic Hepatitis.

BACKGROUND: Alcohol abuse and liver disease are associated with high rates of 30-day hospital readmission, but factors linking alcoholic hepatitis (AH) to readmission are not well understood. We aimed to determine the incidence rate of 30-day readmission for patients with AH and to evaluate potential predictors of readmission. METHODS: We used the Nationwide Readmissions Database to determine the 30-day readmission rate for recurrent AH between 2010 and 2014 and examined trends in readmissions during the study period. We also identified the 20 most frequent reasons for readmission. Multivariate survey logistic regression analysis was used to identify factors associated with 30-day readmission. RESULTS: Of the 61,750 index admissions for AH, 23.9% were readmitted within 30-days. The rate of readmission did not change significantly during the study period. AH, alcoholic cirrhosis, and hepatic encephalopathy were the most frequent reasons for readmission. In multivariate analysis female sex, leaving against medical advice, higher Charlson comorbidity index, ascites, and history of bariatric surgery were associated with earlier readmissions, whereas older age, payer type (private or self-pay/other), and discharge to skilled nursing-facility reduced this risk. CONCLUSIONS: The 30-day readmission rate in patients with AH was high and stable during the study period. Factors associated with readmission may be helpful for development of consensus-based expert guidelines, treatment algorithms, and policy changes to help decrease readmission in AH.

Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors.

OBJECTIVE: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15-3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20-3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05-3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05-3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05-3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11-3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Assessment of the spectrum of hepatic encephalopathy: A multicenter study.

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

Relationship between portopulmonary hypertension and splenectomy: Mayo Clinic experience and review of published works.

AIM: Portopulmonary hypertension is a serious complication of portal hypertension that can lead to right heart failure and death. To our knowledge, an association between portopulmonary hypertension and prior splenectomy has not been described previously. The goals of this study were to describe the frequency of splenectomy in portopulmonary hypertension and compare selected parameters between portopulmonary hypertension subgroups. METHODS: This is a retrospective analysis of patients diagnosed with portopulmonary hypertension between 1 January 1988 and 30 June 2015 at Mayo Clinic (Rochester, MN, USA). We compared age, sex, right ventricle systolic pressure by echocardiography, and right heart catheterization measurements/calculations among subgroups of portopulmonary hypertension patients with splenectomy and/or autoimmune liver disease (autoimmune hepatitis/primary biliary cirrhosis/primary sclerosing cholangitis). RESULTS: The cohort consisted of 141 patients, of whom 8 (6%) had a history of splenectomy prior to the development of portopulmonary hypertension. Twenty-seven (19%) portopulmonary hypertension patients had autoimmune liver disease, and 5 of 8 (62.5%) splenectomized portopulmonary hypertension patients had autoimmune liver disease. No significant difference was noted in right heart catheterization measurements/calculations between splenectomized and non-splenectomized portopulmonary hypertension patients. Right ventricle systolic pressure by echocardiography was significantly higher in those splenectomized. CONCLUSIONS: Prior history of splenectomy in portopulmonary hypertension was 6% in this cohort. The combination of autoimmune liver disease and splenectomy in portopulmonary hypertension was not uncommon. History of splenectomy in patients with portal hypertension and/or autoimmune liver disease may have clinical implications.

Clinical and histopathologic manifestations of solid organ transplantation-associated graft-versus-host disease involving the skin: A single-center retrospective study.

BACKGROUND: Graft-versus-host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature. METHODS: We performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT-associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017). RESULTS: Of nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11-162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0-54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow-up period. CONCLUSIONS: SOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

Hepatocellular Carcinoma Is the Most Common Indication for Liver Transplantation and Placement on the Waitlist in the United States.

BACKGROUND & AIMS: Management strategies for patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) have changed, along with liver allocation policies based on model for end-stage liver disease score. We investigated etiologic-specific trends in liver transplantation in the United States during different time periods. METHODS: We performed a retrospective study, using the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry data, to identify all adult patients registered for liver transplantation in the United States from January 1, 2004, through December 31, 2015. For subjects listed with multiple diagnoses, HCC was considered the primary listing diagnosis. To determine whether availability of direct-acting antiviral agents, which began in 2011, affected pretransplant (death or drop-out) and post-transplant outcomes for patients with HCV infection, we compared data from the time periods of 2004 to 2010 and 2011 to 2014. We used competing-risk analysis to compare differences in end points between these periods. Differences between periods in pretransplantation and post-transplantation outcomes were estimated using Kaplan-Maier analysis and compared using the log-rank test. Associations between year of listing and pre-liver transplant outcome, and year of liver transplant and survival after transplant, were examined using the log-rank test. Proportional hazard regression was used to evaluate the reliability of the time period effect with potential confounders. RESULTS: Among 109,018 registrants, 18.5% were registered for liver transplantation because of HCC. In 2015, HCC was the leading diagnosis among registrants (23.9% of registrations) and recipients (27.2% of recipients). Between 2004 and 2015, the ratio of registrants with vs without HCC increased 5.6-fold for patients with HCV infection, 1.9-fold for patients with hepatitis B virus (HBV) infection, 2.7-fold for patients with alcohol abuse, and 10.2-fold for patients with nonalcoholic steatohepatitis. After adjusting for covariates, we associated the period of 2011 to 2014 with a decreased probability that HCC registrants would undergo liver transplantation (hazard ratio [HR], 0.62; P < .0001). The period of 2011 to 2014 also was associated with a decreased probability of drop-out owing to deterioration or death from HCV-induced (HR, 0.90; P = .0003), HBV-induced (HR, 0.71; P = .002), or alcohol-induced (HR, 0.90; P = .01) liver disease, and an increased probability of delisting as a result of clinical improvement in patients with HCV infection (HR, 3.4; P < .0001), HBV infection (HR, 2.3; P = .004), or alcohol abuse (HR, 2.2; P < .0001). The period of 2011 to 2014 was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients (HR, 0.76; P < .0001). CONCLUSIONS: HCC was the leading indication for liver transplantation in the United States in 2015. Despite this, the probability of liver transplantation decreased the most in registrants with HCC. Pretransplantation and post-transplantation outcomes have improved, particularly in patients with HCV infection.

Embolization of portosystemic shunts for treatment of medically refractory hepatic encephalopathy.

Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003-2015). Patient data collected included the type of HE, medications, Model for End-Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1-4 months), and longer-term (6-12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty-five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1-4 and 6-12 months, respectively. The majority (67%; 8/12) were free from HE-related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE. Liver Transplantation 22 723-731 2016 AASLD.

Evaluation of liver stiffness with magnetic resonance elastography in patients with constrictive pericarditis: Preliminary findings.

PURPOSE: To evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness. MATERIALS AND METHODS: Prospectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t-test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria. RESULTS: Nineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001). CONCLUSION: CP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81-88.

Cardiovascular disease after liver transplantation: When, What, and Who Is at Risk.

The evolution of metabolic and cardiovascular disease (CVD) complications after liver transplantation (LT) is poorly characterized. We aim to illustrate the prevalence of obesity and metabolic syndrome (MS), define the cumulative incidence of CVD, and characterize risk factors associated with these comorbidities after LT. A retrospective review of 455 consecutive LT recipients from 1999 to 2004 with an 8- to 12-year follow-up was performed. Obesity increased from 23.8% (4 months) to 40.8% (3 years) after LT. Increase in body mass index predicted MS at 1 year after LT (odds ratio, 1.1; P < 0.001, per point). CVD developed in 10.6%, 20.7%, and 30.3% of recipients within 1, 5, and 8 years, respectively. Age, diabetes, hypertension, glomerular filtration rate < 60 mL/minute, prior CVD, ejection fraction < 60%, left ventricular hypertrophy, and serum troponin (TN) > 0.07 ng/mL were associated with CVD on univariate analysis. Age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06; P = 0.019), diabetes (HR, 1.78; 95% CI, 1.09-2.92; P = 0.022), prior history of CVD (HR, 2.46; 95% CI, 1.45-4.16; P < 0.001), and serum TN > 0.07 ng/mL (HR, 1.98; 95% CI, 1.23-3.18; P = 0.005) were independently associated with CVD in the long term. Smoking history (ever), sex, hyperlipidemia, and serum ferritin levels were not predictive of CVD. Tacrolimus use versus noncalcineurin-based immunosuppression (HR, 0.26; 95% CI, 0.14-0.49; P < 0.001) was associated with reduced risk of CVD but not versus cyclosporine (HR, 0.67; 95% CI, 0.30-1.49; P = 0.322). CVD is common after LT. Independent of MS, more data are needed to identify nonconventional risk factors and biomarkers like serum TN. Curbing weight gain in the early months after transplant may impact MS and subsequent CVD in the long term.

Effect of the pretransplant serum sodium concentration on outcomes following liver transplantation.

Hyponatremia is associated with an increased risk of mortality on the liver transplantation (LT) waiting list. Although the incorporation of the serum sodium (Na) level into the Model for End-Stage Liver Disease score may reduce wait-list mortality, concerns remain about a potential association between pre-LT hyponatremia and decreased post-LT survival. Furthermore, the relationship between pre-LT hypernatremia and post-LT survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum of pre-LT serum Na levels on post-LT outcomes. We identified 19,537 patients from 2003 to 2010 for whom serum Na levels immediately before LT were available. The patients were divided into 3 groups [hyponatremic (Na ≤ 130 mEq/L), normonatremic (Na = 131-145 mEq/L), and hypernatremic (Na > 145 mEq/L)], and their post-LT outcomes were compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and patients with normonatremia. A fraction of the patients (2.4%) had hypernatremia, which was associated with increased in-hospital mortality (11.2% versus 4.2%, P < 0.001) and diminished 90-day survival (86.4% versus 94.0.%, P < 0.001). After adjustments for important clinical variables, the association of pre-LT hypernatremia with posttransplant mortality remained significant with a hazard ratio of 1.13 for each unit increase in the Na level > 145 mEq/L (P < 0.001). The duration of the hospitalization after LT was significantly longer for hypernatremic patients (P < 0.001). In conclusion, hyponatremia per se does not affect post-LT survival. Pre-LT hypernatremia is a highly significant risk factor for post-LT mortality.

From vitamin K antagonists to liver international normalized ratio: a historical journey and critical perspective.

Adoption of international normalized ratio (INR) to harmonize prothrombin time has greatly improved the safety and effectiveness of vitamin K antagonists (VKA) oral anticoagulant therapy. INR is also a major laboratory variable in calculating the widely used Model for End-Stage Liver Disease (MELD) score for liver transplant organ prioritization. However, since the conventional INR (INRVKA) is calibrated specifically for VKA patients, its interlaboratory variation has a significant impact on the accuracy of MELD score. Though still requiring further clinical validation in large numbers of waitlisted patients, the alternative liver INR calibrated by using plasma from liver disease patients instead of VKA patients may harmonize the differences and thus more suitable for MELD score calculation. The objective of this article is to review the history of INR, MELD score, and liver INR, and discuss the challenges and solutions of liver INR implementation.

Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for diagnosis and therapeutic interventions in recipients of liver transplantation (LT) who develop biliary complications. Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PEP) is the most common major adverse event after ERCP; however, the frequency of PEP in LT recipients is not well established. We aimed to determine the rate of PEP in this population and to identify its predictors, especially among immunosuppressive agents. We reviewed all ERCP procedures performed in LT recipients after duct-to-duct biliary anastomoses at 2 high-volume transplant centers. Patients who had undergone sphincterotomy or had a surgically altered pancreaticobiliary anatomy before LT were excluded. Electronic medical records and endoscopy databases were used to obtain clinical, endoscopic, and medication data. A multivariate logistic regression analysis was used to determine predictors of PEP in this cohort. In all, 730 ERCP procedures were performed in 301 patients during the study period with an observed PEP rate of 3% (22/730). A univariate analysis revealed an increased risk of PEP with index ERCP after LT [odds ratio (OR) = 4.04, 95% confidence interval (CI) = 1.40-11.65] and in cases with difficult biliary cannulation (OR = 2.89, 95% CI = 1.10-7.65), whereas prednisone use was found to have a protective effect in both univariate (OR = 0.34, 95% CI = 0.14-0.84) and multivariate analyses (OR = 0.22, 95% CI = 0.09-0.57) after adjustments for difficult biliary cannulation and post-LT index ERCP. This retrospective analysis demonstrates that corticosteroid therapy has a protective role in the development of PEP in LT recipients. Further studies are warranted to confirm our findings.

Immunizations in chronic liver disease: what should be done and what is the evidence.

Infections are common in patients with chronic liver disease, especially those with cirrhosis. Patients with advanced liver disease, who develop bacterial infections, are at a substantially higher risk of death. As liver disease progresses, most immunizations lose their effectiveness. Overall, it is important to address immunization needs in patients with chronic liver disease early on, when immunizations are most effective. Inactivated or killed-type vaccinations rather than live, attenuated vaccinations are always preferable in patients with cirrhosis. The influenza vaccination is less effective in patients with cirrhosis and in the early post-liver transplant setting as compared to healthy individuals. The influenza vaccination may prevent hepatic decompensation, but further data are needed to confirm this. Yearly inactivated influenza vaccinations should be provided to those with chronic liver disease. The pneumonia vaccination is less effective in patients with cirrhosis, with a further decline in protective serologies after liver transplantation. Standard guidelines for the administration of Pneumovax23 for immunocompromised hosts apply to patients with chronic liver disease. Chronic liver disease also leads to higher non-response rates to the hepatitis B vaccination. Early-stage chronic liver disease patients should receive conventional hepatitis B series. Cirrhotics benefit from a double-dose hepatitis B vaccination at standard intervals. Hepatitis A superimposed on chronic viral hepatitis or chronic liver disease increases risk of mortality. Hepatitis A vaccination effectiveness wanes in cirrhosis, and should if possible be given before the development of cirrhosis. More data are needed for routine use of herpes zoster and human papillomavirus in chronic liver disease.