Transgender Males on Gender-Affirming Hormone Therapy and Hepatobiliary Neoplasms: A Systematic Review.

OBJECTIVE: Behavioral therapy, gender-affirming hormone therapy (GAHT), and surgery are all components of a successful gender transition, but due to a historical lack of access, there is paucity of long-term data in this population. We sought to better characterize the risk of hepatobiliary neoplasms in transgender males undergoing GAHT with testosterone. METHODS: In addition to the 2 case reports, a systematic literature review of hepatobiliary neoplasms in the setting of testosterone administration or endogenous overproduction across indications was conducted. The medical librarian created search strategies using keywords and controlled vocabulary in Ovid Medline, Embase.com, Scopus, Cochrane Database of Systematic Reviews, and clinicaltrials.gov. A total of 1273 unique citations were included in the project library. All unique abstracts were reviewed, and abstracts were selected for complete review. Inclusion criteria were articles reporting cases of hepatobiliary neoplasm development in patients with exogenous testosterone administration or endogenous overproduction. Non-English language articles were excluded. Cases were collated into tables based on indication. RESULTS: Forty-nine papers had cases of hepatocellular adenoma, hepatocellular carcinoma, cholangiocarcinoma, or other biliary neoplasm in the setting of testosterone administration or endogenous overproduction. These 49 papers yielded 62 unique cases. CONCLUSION: Results of this review are not sufficient to conclude that there is an association between GAHT and hepatobiliary neoplasms. This supports current evaluation and screening guidelines for initiation and continuation of GAHT in transgender men. The heterogeneity of testosterone formulations limits the translation of risks of hepatobiliary neoplasms in other indications to GAHT.

Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation.

BACKGROUND: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS: Single-center retrospective cohort study of SOT recipients. RESULTS: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.

Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.

UNLABELLED: Hepatitis C virus (HCV)-mediated liver diseases are one of the major health issues in the United States and worldwide. HCV infection has been reported to modulate microRNAs (miRNAs) that control various cell surface receptors and gene-regulatory complexes involved in hepatic inflammation and liver diseases. We report here that specific downregulation of miRNA-107 and miRNA-449a following HCV infection in patients with HCV-mediated liver diseases modulates expression of CCL2, an inflammatory chemokine upregulated in patients with chronic liver diseases, by targeting components of the interleukin-6 receptor (IL-6R) complex. Computational analysis for DNA-bound transcription factors in the CCL2 promoter identified adjacent binding sites for CCAAT/CEBPα, spleen focus-forming virus, proviral integration oncogene (SPI1/PU.1), and STAT3. We demonstrate that CEBPα, PU.1, and STAT3 interacted with each other physically to cooperatively bind to the promoter and activate CCL2 expression. Analysis of IL-6R and JAK1 expression in HCV patients by quantitative PCR showed significant upregulation when there was impaired miRNA-107 and miRNA-449a expression, along with upregulation of PU.1 and STAT3, but not CEBPα. miRNA-449a and miRNA-107 target expression of IL-6R and JAK1, respectively, in vitro and also inhibit IL-6 signaling and impair STAT3 activation in human hepatocytes. Taken together, our results demonstrate a novel gene-regulatory mechanism in which HCV-induced changes in miRNAs (miRNA-449a and miRNA-107) regulate CCL2 expression by activation of the IL-6-mediated signaling cascade, which we propose will result in HCV-mediated induction of inflammatory responses and fibrosis. IMPORTANCE: Hepatitis C virus (HCV)-induced hepatitis is a major health concern worldwide. HCV infection results in modulation of noncoding microRNAs affecting major cellular pathways, including inflammatory responses. In this study, we have identified a microRNA-regulated pathway for the chemokine CCL2 in HCV-induced hepatitis. Understanding microRNA-mediated transcriptional-regulatory pathways will result in development of noninvasive biomarkers for better disease prediction and development of effective therapeutics.

Liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasing problem in the USA and worldwide. Current treatments for HCC include chemoembolization, radioembolization, liver resection, and liver transplantation in the setting of selected cirrhotic patients. Liver transplantation for HCC was controversial initially, but is now widely accepted as a curative approach. Cirrhotic patients who meet standards for transplantation and have a tumor burden within Milan criteria are eligible for transplantation and receive Model for End-Stage Liver Disease (MELD) exception points once listed. Given the decline in availability of donor organs, rewarding MELD exception points and performing liver transplants in these patients remain controversial. Despite this, various guidelines propose expanding eligibility criteria for cirrhotics with HCC, due to post-transplant outcomes comparable to patients transplanted without HCC. Following the transplant, issues include optimizing the type and amount of immunosuppression and screening for and treating recurrence of HCC.

Assessment of hepatitis C risk factors and infection prevalence in a jail population.

OBJECTIVES: We sought to validate previous reports of HCV prevalence in jails, identify HCV risk factors prevalence, and identify risk factors associated with HCV infection in this population. METHODS: Inmates at the Buzz Westfall Justice Center (BWJC) in St. Louis, Missouri, were offered risk factor screening for HCV and anti-HCV antibody testing from December 2012 through May 2013. Demographic and risk factor information were assessed for significant associations with positive HCV antibody results. Risk factors that were significantly associated in univariate analysis were assessed using binary logistic regression to model the relationship between positive HCV results and the risk factors and demographics. RESULTS: Fifty of 304 inmates were positive for HCV, with a prevalence of 16.4%. The risk factors significantly associated with increased risk for positive HCV antibody were age (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.04, 1.15 for each year), injection drug use (OR = 53.87; 95% CI = 17.78, 163.21), sex with HCV-positive partner (OR = 7.35; 95% CI = 1.41, 38.20), and tattoos by a nonlicensed provider (OR = 2.62; 95% CI = 1.09, 6.33). Prevalence for women was 3 times that of men (38% vs 12%). CONCLUSIONS: Prevalence of HCV at BWJC was similar to previous jail studies, which is lower than reported prison rates and higher than the general population.

Liver volume in the cirrhotic patient: does size matter?

BACKGROUND: While it is established that cirrhosis results in a decrease in liver volume (LV), whether LV itself predicts patient survival is unknown. We hypothesize that estimated LV is an important prognostic indicator in patients with cirrhosis. METHODS: Data was gathered retrospectively from consecutive patients evaluated for a liver transplant from January 2001 to June 2006. Of 500 patients identified, 323 patients met both inclusion and exclusion criteria. LV per ideal body weight (IBW) was used to correct for body size, and LV/IBW was stratified by median split for survival analyses. Patients were classified into one of three clinical groups: hepatocellular disease (n = 229), cholestatic disease (n = 56), and miscellaneous (n = 38). One of three possible clinical outcomes (survival, liver transplantation, or death) was recorded during the 5-year follow-up, the latter two grouped together as "transplant/death." RESULTS: Transplant/death occurred in 283 (88 %) subjects. Overall, there was a significant increase in transplant/death in those with lower LV/IBW (χ(2) = 5.27, p = 0.022). When considering the subset with hepatocellular disease, lower LV/IBW was a robust predictor of transplant/death (χ(2) = 9.62, p = 0.002). In multivariate analyses, the LV/IBW trended toward predicting transplant/death (ExpB = 0.943, p = 0.053) independent of Model for End stage Liver Disease (MELD) (ExpB = 1.13, p = 0.001). DISCUSSION: LV has important predictive value in patients with cirrhosis from hepatocellular disease. This observation appears to be independent of MELD, suggesting LV may impart important prognostic information that is not captured by the MELD score alone. Thus, LV may serve as an important adjunct to the MELD score in patients with hepatocellular disease.

Parenchymal alterations in cirrhotic livers in patients with hepatopulmonary syndrome or portopulmonary hypertension.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are distinct pulmonary vascular complications of cirrhosis. Little is known about possible associated hepatic histopathological features. Explanted livers from patients clinically diagnosed with HPS (n = 8) or PPH (n = 7) and cirrhotic explants from controls (n = 30) without HPS or PPH were evaluated with trichrome histochemistry, anti-glutamine synthetase (anti-GS), and anti-CD34 immunohistochemistry (IHC). Trichrome stains were characterized by cirrhotic nodules (CNs) of various sizes, including incomplete septal cirrhosis (ISC). ISC was overrepresented in the HPS (4/8 or 50%) and PPH livers (3/7 or 43%); in addition, neither group had micronodular cirrhosis. The control explants showed the entire spectrum of nodules: micronodular, macronodular, mixed CNs, and ISC (P = 0.04). The variability of cirrhosis severity was shown with the Laennec grading system (0-6). The cirrhosis of the majority of the HPS (6/8) and PPH livers (6/7) was scored as mild, whereas the control explants were more evenly distributed across the mild (14/30) and moderate/severe grades (16/30). GS positivity was retained in a perivenular location as the dominant pattern in each explant group. CD34 staining detected capillarized sinusoids of CNs as well as vascular channels within septa, but no significant differences were found between the groups. None of the observed light microscopy or histochemistry and IHC patterns showed a correlation with the underlying liver disease. Although our results demonstrate variable architectural and vascular remodeling within and between explant livers regardless of the presence or types of pulmonary complications, there were differences in explants with HPS or PPH versus controls that correlated with less severe cirrhosis.

Once weekly fluconazole for antifungal prophylaxis post-liver transplantation.

BACKGROUND: Invasive fungal infections (IFI) remain a significant cause of morbidity and mortality in orthotopic liver transplantation (OLT) recipients. In this retrospective study, the outcomes of a protocol using once weekly fluconazole for 3 months after OLT in low- and high-risk patients were reviewed. METHODS: In total, 221 OLTs were evaluated in the 3-year period after institution of the new protocol to determine the incidence of IFI within 6 months post-OLT. RESULTS: In this cohort, 11 IFIs developed during the 6-month post-transplant period, with the majority being non-albicans Candida. High-risk patients had a greater rate of IFI (16.7% versus 3.4%, P = 0.038) and a significantly longer intensive unit care (ICU) and hospital lengths of stay compared with low-risk patients. Patient and graft survival were similar between the groups. Our patient population appeared to be at low risk for IFI, with 92% of the entire cohort considered low risk. DISCUSSION: Given the low incidence of IFI in the low-risk group and the possibility of such protocol selecting out for fluconazole-resistant fungi, the use of weekly fluconazole for 3 months may not be justifiable in low-risk OLT recipients. Given the increased resource utilization observed with IFI, further examination of a more intensive prophylactic strategy in high-risk patients may be warranted.

Immune response to extracellular matrix collagen in chronic hepatitis C-induced liver fibrosis.

Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h) 2) and T helper 17 (T(h) 17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly T(h) 2 and T(h) 17 cytokine profile.

The psychiatric diagnosis of alcohol abuse and the medical diagnosis of alcoholic related liver disease: effects on liver transplant survival.

The present study investigated whether differing diagnostic criteria for alcoholism used by mental health professionals versus hepatologists lead to different outcomes in predicting liver transplant survival as determined by the medical record and without a priori judgments. This was in contrast to past studies, particularly in the liver transplant literature, demonstrating comparable survival rates between alcoholics and non-alcoholics that have typically employed a diagnosis of Alcoholic Liver Disease (ALD), which does not capture the salient maladaptive behavioral and interpersonal features associated with DSM-IV-TR diagnoses of Alcohol Abuse (AA) and Alcohol Dependence (AD). A series of survival analyses were conducted using data culled from the psychological and medical records of 358 first-time liver transplant recipients at Barnes-Jewish Hospital in St. Louis, Missouri. The primary outcome investigated was liver graft survival following transplant surgery. Follow-up times varied from 0 days to 13 years, depending on the time of transplant and length of graft survival, with a median follow-up time of 6.2 years. Diagnoses of AA and AD predicted significantly poorer survival rates, while diagnoses of ALD did not. DSM-IV-TR alcoholism criteria appear to have greater utility for predicting survival differences beyond pathophysiologically defined alcoholic liver failure.

Liver transplantation for hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study.

INTRODUCTION: Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT). METHODS: Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014-2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) RESULTS: 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for "condition improved" (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's. CONCLUSIONS: DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.

Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation.

PURPOSE: To evaluate outcomes of downstaging patients with advanced (American liver tumor study group stage III/IV) hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) to allow eligibility for orthotopic liver transplant (OLT). METHODS: From 1999 to 2006, 202 patients with HCC were referred for transplant evaluation. Seventy-six (37.6%) patients with stage III/IV HCC were potential transplant candidates if downstaging was achieved by TACE. OLT was considered based on follow-up imaging findings. The number of patients who were successfully downstaged within the Milan criteria, tumor response using Response Evaluation Criteria in Solid Tumors criteria, findings at explant, and outcomes after transplant were tracked. RESULTS: Eighteen of 76 (23.7%) patients had adequate downstaging to qualify for OLT under the Milan criteria. By Response Evaluation Criteria in Solid Tumors, 27/76 (35.5%) patients had a partial response, 22/76 (29%) had stable disease, and 27/76 (35.5%) had progressive disease. Seventeen of 76 (22.4%) patients who met other qualifications underwent OLT after successful downstaging (13/38 stage III;4/38 stage IV). Explant review demonstrated 28 identifiable tumors in which post-TACE necrosis was greater than 90% in 21 (75%). At a median of 19.6 months (range 3.6-104.7), 16/17 (94.1%) patients who underwent OLT are alive. One patient expired 11 months after OLT secondary to medical comorbidities. One of 17 (6%) OLT patients had recurrent HCC. This patient underwent resection of a pulmonary metastasis and is alive, 63.6 months from OLT. CONCLUSION: Selected patients with stage III/IV HCC can be downstaged to Milan criteria with TACE. Importantly, patients who are successfully downstaged and transplanted have excellent midterm disease-free and overall survival, similar to stage II HCC.

Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection.

BACKGROUND: Alpha-fetoprotein has been used as a predictor of recurrence for hepatocellular carcinoma and disease-free survival post-resection. Studies in East Asia have shown that serum alpha-fetoprotein per total tumor volume ratio is a better prognostic indicator than alpha-fetoprotein alone. Similar studies in the United States evaluating serum alpha-fetoprotein to total tumor volume ratio have not been conducted. Its relevance is incompletely understood. METHODS: Consecutive patients undergoing resection for hepatocellular carcinoma at a single tertiary center between 2000 and 2013 were identified for inclusion in this retrospective cohort study. Patient demographics, associated liver disease, Child-Pugh and Model for End-Stage Liver Disease scores, preoperative imaging, surgical pathology, alpha-fetoprotein at diagnosis, last alpha-fetoprotein before surgery, and peak alpha-fetoprotein levels were recorded. Actual tumor volume by imaging volumetrics was used when available (n = 70). For the remaining cases, total tumor volume was calculated using the sum of the volumes of all the tumors ((4/3)πr3) where "r" is the mean radius of each lesion. Peak serum alpha-fetoprotein was used to calculate the alpha-fetoprotein to total tumor volume ratio. RESULTS: A total of 124 patients resected for hepatocellular carcinoma between 2000 and 2013 were identified. Overall 1-, 3-, and 5-year survival post resection was 76%, 53%, and 35%, respectively. On multivariate analysis, peak alpha-fetoprotein to total tumor volume ratio > 20 (P < .001, HR = 3.72, 95% CI [1.82-7.58]) and lymphovascular space invasion (P = .002, HR = 3.30, 95% CI [1.57-6.94]) were found to affect hepatocellular carcinoma recurrence-free survival. CONCLUSION: A variety of prognostic values predict the recurrence of hepatocellular carcinoma postresection. Peak preoperative alpha-fetoprotein to total tumor volume > 20 and lymphovascular space invasion has been shown to predict recurrence of hepatocellular carcinoma. Our study confirms findings from East Asian studies. But larger series are needed to establish this correlation in patients with hepatocellular carcinoma not treated by resection.

Management of hepatitis C in the setting of liver transplantation.

Each year, 5000 to 6000 liver transplantations are performed in the United States, 40% of which are for hepatitis C-related end-stage liver disease. Infection of liver allograft is universal and is associated with an accelerated rate of disease progression. Unfortunately, antiviral therapy after transplantation is less effective and often is beset with complications. This article reviews antiviral therapies and the factors that may influence the response in patients who have HCV infection both immediately before and after liver transplantation.

Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival.

BACKGROUND: Preorthotopic liver transplantation locoregional therapy (LRT) for hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting orthotopic liver transplantation (OLT). In this study, we investigated the efficacy of LRT as a strategy to improve longterm survival after transplantation. STUDY DESIGN: A retrospective analysis of prospectively collected data identified 100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46 received LRT in the form of transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or a combination of these. RESULTS: The 1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%, respectively. Demographic data and waiting time for OLT were similar between LRT and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74 versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p = 0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01), but this improvement was observed in patients with HCC stages II, III, and IV (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated, revealed complete tumor necrosis with no viable tumor cells on explant pathology (pT0). These patients did not experience any longterm recurrence, in contrast to those with similar pre-OLT tumors. CONCLUSIONS: OLT is a viable treatment option for primary HCC. LRT substantially downstages the primary tumor and improves longterm survival in patients with advanced disease. Complete tumor necrosis with LRT is associated with excellent longterm recurrence-free survival.

Is tube feeding an option in patients with liver disease?

Tube feeding in patients with liver disease is often approached with trepidation because of fears of bleeding with tube placement due to the presence of esophageal varices or coagulopathy. However, the amount of published data supporting these fears is limited. This manuscript examines the issues surrounding tube feedings in patients with liver disease.

Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.

BACKGROUND: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition. OBJECTIVE: To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure. DESIGN: Prospective cohort study. SETTING: 17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group. PATIENTS: 308 consecutive patients with acute liver failure, admitted over a 41-month period. MEASUREMENTS: Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission. RESULTS: 73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not. CONCLUSIONS: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.

Motion - patients with primary sclerosing cholangitis should undergo early liver transplantation: arguments against the motion.

Liver transplantation is an accepted form of treatment for patients with primary sclerosing cholangitis (PSC) and can provide long term survival. Cholangiocarcinoma occurs in 10% to 20% of patients with PSC, is difficult to diagnose and has a poor prognosis. It has been proposed that liver transplantation be undertaken early in the course of the PSC, before cancer develops. Such a proposal would have significant implications for the method of assigning priority to patients awaiting liver transplantation. Other patients on the waiting list would experience further delays, while there is no proven benefit for PSC patients. Few patients with this disease are removed from the waiting list because they developed cancer. If one were to state that PSC patients warrant special consideration because of the hypothetical risk of cholangiocarcinoma, the same argument could be applied to patients with hepatitis C and other causes of cirrhosis, who are at increased risk of hepatocellular carcinoma. The transplant allocation system is applied in an equitable fashion to patients with a large variety of liver diseases. Alteration of this system to benefit a small number of patients with PSC would violate the principles on which it was created, and cannot be justified.

Aortic balloon valvuloplasty prior to orthotopic liver transplantation: a novel approach to aortic stenosis and end-stage liver disease.

The combination of severe aortic stenosis and end-stage liver disease increases the morbidity and mortality of surgical aortic valve replacement or orthotopic liver transplantation resulting in a prohibitive operative risk. We propose a staged approach of balloon aortic valvuloplasty prior to orthotopic liver transplantation as a bridge to definitive aortic valve replacement. Between 2010 and 2012, four patients with severe aortic stenosis and end-stage liver disease underwent staged balloon aortic valvuloplasty followed by orthotopic liver transplantation. All patients had been deemed to be inappropriate candidates for liver transplantation or aortic valve surgery due to their comorbidity. One patient died of complications from a perivalvular abscess. Three patients went on to successful graft implantation and function and surgical recovery. Two of the three patients proceeded to definitive surgical aortic valve replacement with the remainder currently undergoing evaluation. In this case series, we present a novel approach of balloon aortic valvuloplasty prior to liver transplantation as a potential bridge to definitive treatment of severe aortic stenosis in the end-stage liver patient.