OLT Candidates Research Articles

P343 VALIDATION OF ESC 2014 GUIDELINES PROTOCOL FOR CORONARY ARTERY DISEASE DETECTION IN PATIENTS CANDIDATES TO LIVER TRANSPLANTATION

Abstract Introduction Orthotopic liver transplantation (OLT) is the only effective treatment in patients with end–stage liver disease. Coronary artery disease (CAD) is associated with increased peri–operative OLT mortality. Thus, identification of CAD is crucial in pre–OLT evaluation. There is not a specific pre–OLT accepted diagnostic algorithm for CAD detection. 2014 ESC guidelines for non–cardiac surgery management consider OLT as a high–risk abdominal surgery and only patients with CAD history, suspected symptoms and low exercise capacity are invited to undergo to specific functional exams such as stress–echo. Purpose of the present study was to compare the ESC protocol with our cardiologic pre–OLT protocol, in which tests of ischemia and coronary CT are largely administered on based on presence of risk factors. Methods. From 2014 to 2021 all OLT candidates have been evaluated by visit, electrocardiography, rest and, when possible, stress echocardiography. In subject aged > 50 years with diabetes and/or two or more of the following risk factors: smoking, CAD family history, peripheral vascular disease, CT was performed. CGF was scheduled when CAD history and typical symptoms of angina. We theoretically re–analyse our database in order to consider the potential destiny of each patient in case of application of ECS 2014 protocol. We were able to calculate the differences in the number of potentially loss CAD diagnosis. Results. 367 patients (58.2%, age 57±5.7 years, males 74%) underwent OLT. Stress Echo was performed in 239 (65.1%) and positivity was found in 24 pz (6,5%). Coronary CT was performed in 95 (25,8%). CGF was performed in 75 patients (20.1%), 38 (9,2%) directly for known CAD and/or symptoms. Critical coronary lesions were found in 12 patients (3,2 %): 7 revascularized by PTCA, 1 by CABG and 4 medically managed, 25 patients had non critical lesions (7.8%), 31 patients (9.6%) referred to CGF were subsequently removed by transplant list, whereas OLT was successfully performed in PTCA patients (n = 8). During follow–up (35±20 months) 28 patients died (14.2%), 5 with symptoms of congestive heart failure, but no ischemic events were observed. Conclusions CAD detectionis remains a clinical challenge in candidates to OLT. The large number of normal stress echoes and normal CGF, even in presence of cardiovascular risk factors, demonstrates that CAD prevalence in ESLD is no higher than in general population, but a gold method to detect CAD is still unclear.

Standardized measures of frailty predict hospital length of stay following orthotopic liver transplantation for hepatocellular carcinoma.

Frailty in liver transplant (LT) waitlisted patients has been shown to predict waitlist mortality. While not currently used to allocate organs, the relationship between preoperative frailty and postoperative outcomes following orthotopic LT needs further elucidation. We determined the frailty status of 50 OLT candidates listed for hepatocellular carcinoma (HCC) and examined relationships between frailty and outcomes on the waitlist and, if transplanted, 30-day mortality, hospital length of stay (LOS), ICU LOS, and several other secondary outcomes. The overall prevalence of frailty was 30%, and the median natural MELD score for patients was 13. The overall hospital LOS for the frail group was longer (14.5days [IQR 12-19]) as compared to the non-frail group (8days [IQR 7-13]); P=.015. Groups also differed in the time to their first PT session (6days [IQR 4-15] for the frail vs 4days [IQR 3-7] for the non-frail patients; P=.042). There was no statistically significant difference in other outcomes measures, including ICU LOS and 30-day mortality. Frailty in OLT patients with diagnosed HCC is a predictor of longer hospital stay and longer time to the first completed PT session independent of preoperative MELD scores.

Multiple Ways to Manage Portal Thrombosis During Liver Transplantation: Surgical Techniques and Outcomes

BackgroundPortal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. Materials and MethodsWe performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. ResultsAmong the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). ConclusionAlthough PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

Extracorporeal Membrane Oxygenation as Bridge to Lung Transplantation

Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in selected patients with satisfactory long-term results. However, the paucity of available donors engenders a prolonged stay on the waiting list with progressive decline of lung function. In cases of sudden respiratory failure, admission to an intensive care unit with institution of extracorporeal membrane oxygenation (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we started ECMO because of acute decline of lung function. Eleven patients had cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral OLT was performed after a mean waiting time of 6 days from ECMO institution; 5 patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2 patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient died in the perioperative period and 1-year survival was 85.7%. ECMO represents a valid option as a bridge to urgent OLT for selected candidates.

Recurrence after liver transplantation for hepatocellular carcinoma according to up-to-seven criteria.

The Up7 criteria for HCC have recently emerged to identify potential candidates for OLT. The aim of this study was to assess the validity of the Up7 criteria according to the pathological analysis of the explanted livers. For recurrence risk calculation 669 HCC transplanted patients were classified according to both the pathological Milan and Up7 criteria. In order to identify potential predictors of recurrence, selected biological tumor markers and morphological features were then tested by Cox regression. The 5-year HCC recurrence rate for the Milan out/Up7 in subgroup (n=87), was significantly higher than patients meeting Milan criteria (n=299), 15.8% vs. 9.4% (p=0.0290). For patients within the Up7 criteria (n=383), only pre-OLT AFP level >1000ng/mL and microvascular invasion were significant predictors for recurrence, and for those beyond the Up7 criteria (n=286), pre-OLT AFP level >1000ng/mL, poor differentiation grade and microvascular invasion remained significant. Compared to the current Milan staging system, HCC patients within the pathological Up7 criteria were associated with a higher, but acceptable risk of recurrence after OLT, and along with tumor burden, other parameters can potentially be used for further refinement of HCC staging, such as AFP levels and microvascular invasion.

Liver Failure and the Need for Transplantation in 6 Patients With Hepatoportal Sclerosis

Hepatoportal sclerosis (HPS), first reported by Mikkelsen et al in 1965, is a pathologic condition that does not cause cirrhotic portal hypertension. The primary hepatic lesion in HPS is found in portal vein branches with preserved synthetic function. Rarely do patients with HPS need liver transplantation. The aim of this study was to describe the clinical and pathologic features of 6 HPS cases who underwent liver transplantation (OLT). From 2000 to 2008, 6 OLT candidates were diagnosed with HPS: 3 displayed bleeding varices and 4 ascites. Child-Pugh evaluation was class B (n = 4) or C (n = 2). The Model for End-stage Liver Disease scores were 18 (n = 2), 20 (n = 3), and 22 (n = 1). Cirrhosis resulted from presumed diagnoses of alcohol n = (1), autoimmune n = (2) or cryptogenic cirrhosis n = (3). On histologic examination, there was marked phlebosclerosis in all cases, including nonocclusive portal vein thrombosis (n = 3), intense portal fibrosis (n = 1), moderate portal fibrosis (n = 5), and uniform moderate sinusoidal dilatation without megasinusoid formation, but with ductal biliary proliferation and ductal biliary fibrosis in all cases. Cholestasis was observed in 1 and incomplete septal cirrhosis in 4 cases. None of the subjects showed histological features of the presumed underlying liver disease. The overall survival of this group was no different from that of other OLT patients. HPS causing hepatic failure may require liver transplantation. Fhlebosclerosis andportal fibrosis may contribute to the loss of hepatic synthesis leading to the need for hepatic transplant. Significant portal fibrosis and phlebosclerosis can contribute to hepatic parenchymal and posterior synthetic loss.

Prevalence of Hepatitis B and A Virus Markers and Vaccination Indication in Cirrhotic Patients Evaluated for Liver Transplantation in Spain

In the absence of immunity, vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic liver disease and those evaluated for liver transplantation (OLT) HAV and HBV infections after OLT which are frequent in this setting, are associated with a worse prognosis. The aim of this study was to estimate the need for vaccination against HBV and HAV among cirrhotic patients who were candidates for OLT and associations with gender, age, and etiologic factors. HBV and HAV serological markers HBsAg, anti-HBc, antiHBs, immunoglobulin G (IgG)-anti-HAV were investigated among 568 patients, including 75% men. The overall mean age was 53.6 ± 8.9 years range 17–69, and 20% were diabetic. This etiologies were alcohol (68%), hepatitis C virus (35%) or other causes (10.4%). Child-Pugh classes were: A (26%), B (44%), and C (30%). In contrast with 359 patients (63.2%) who had negative HBV markers, 209 (36.8%) were positive: HBsAg (+), 43 (7.6%), isolated anti-HBc (+), 57 (10%), isolated anti-HBs (+), 19 (3.3%), anti-HBc (+)/anti-HBs (+), 90 (15.8%). HBV vaccine indication was performed in 416 patients (73.2%) who either had negative HBV markers or isolated anti-HBc (+). It was more frequently performed in women (82.3% versus 70.3%, P = .005), albeit with no differences according to age or etiology. There were only 8.2% (44/538) IgG-anti-HAV-negative, an indication for vaccination against HAV, which was more frequent affecting patients who were younger [≤45 years (27.6%), 46–55 (7.2%), >55 (2.6%); P < .0001)]; nondiabetic (9.5% versus 2.8%, P = .023); nonalcoholic (11.4% versus 6.6%, P = .056); and displayed negative HBV markers (10.2% versus 4.6%, P = .023). Only three patients with IgG-anti- HAV (−) were over 60 years. In conclusion, there is a frequent indication for HBV vaccination among cirrhotic and especially HAV vaccine for under 45 year old patients undergoing evaluation for OLT.

Cystatin C Level as a Predictor of Death and Cardiovascular Events After Liver Transplantation

Background The diagnosis of renal failure is important in cirrhosis. Cystatin C (Cys) has been suggested not only to be a sensitive marker of renal function, but also a stronger predictor of the risk of death and cardiovascular events in heart failure. Our aims were to investigate plasma Cys concentrations for the detection of moderately impaired renal function and its association with mortality and cardiovascular events among cirrhotic patients after liver transplantation (OLT). Methods Clinical and biochemical data, including Cys levels, were analyzed in 99 cirrhotic candidates for OLT. We recorded cardiovascular events. Results Receiver-operator characteristics curves showed a similar efficiency to detect a creatinine clearance <60 mL/min per 1.73m 2 (Cys = 0.753; creatinine [Cr] = 0.799; glomerular filtration rate [GFR, Cockcroft–Gault formula] = 0.842; urea = 0.823; P = .001). However, at cutoff concentrations of 1.3 mg/dL, Cr showed great specificity (96%) but poor sensitivity (13%), while the sensitivity of Cys was superior (83%) with moderate specificity (55%) at a cutoff of 1400 ng/mL. Over a median follow-up of 2.7 years, 14 patients developed a cardiovascular event, including, 11 who displayed Cys levels >1400 ng/mL before OLT, showing a significant difference ( P < .05) compared to patients who showed no cardiovascular event. Kaplan–Meier analysis Cys discriminated significantly better than the Model for End-Stage Liver Disease score between survivors and nonsurvivors ( P < .05). Conclusion Cys determinations could be a valuable tool for early diagnosis of renal dysfunction among cirrhotic patients. Furthermore, it may predict the risk of death and cardiovascular events after OLT.

Chronic Kidney Disease–Epidemiology Formula and Model for End-Stage Liver Disease Score in the Assessment of Renal Function in Candidates for Liver Transplantation

Assessment of renal function in patients with end-stage liver disease (ESLD) awaiting liver transplantation (OLT) is critical. Various conditions may cause renal damage in ESLD. Renal and liver functions are intertwined due to splanchnic hemodynamic relationships; renal failure rarely occurs in patients without advanced decompensated cirrhosis. The recent literature suggests that evaluation of renal function should include an assessment of liver function. The aim of this study was to evaluate different methods to estimate glomerular filtration rate (GFR) in patient among ESLD candidates for OLT over 1 year. We also correlated renal and hepatic functions. Fifty-two cirrhotic patients Model for End-Stage Liver Disease [MELD] > 10) were enrolled in the study. All patients were evaluated at baseline and every 4 months (T1–T4) thereafter for 1 year. The GFR was calculated by creatinine clearance, and estimated by Cockroft and Gault, Modified Diet Renal Disease (MDRD) 4 and 6 variable and Chronic Kidney Disease-Epidemiology (CKD-EPI) formulae. Hepatic functions were evaluated by MELD score, albumin, bilirubin, and International Normalized Ratio (INR). We observed not statistically significant increase mean value of MELD score, bilirubin, serum creatinine, and blood urea nitrogen and a reduced serum sodium. There were no significant differences among various methods to evaluate GFR at each time over 1 year. We did not observe any association between renal and hepatic function, except at T4 for MELD and GFR estimated with MDRD 4 ( P = .009) and 6 ( P = .008) parameters or CKD-EPI ( P = .036), and MELD and sodium ( P = .001). Our results showed that evaluation of renal function in cirrhosis should include an evaluation of hepatic function. In our case, MDRD and CKD-EPI seemed to be the more accurate formulae to evaluate renal function in relation to hepatic function.

Liver transplantation in HIV-1-infected patients

With the advent of highly active antiretroviral therapy in 1996, patients infected with HIV are now living longer and dying from illnesses other than acquired immunodeficiency syndrome (AIDS). Liver disease due to chronic hepatitis B and C is now a leading cause of mortality among HIV-infected patients in the developed world. For these patients, liver transplantation (OLT) is the only therapeutic option and HIV infection alone is not a contraindication. The current HIV selection criteria for HIV-infected OLT candidates are as follows: 1) ideally no history of opportunistic infections or HIV-related cancer, although some treatable and preventable opportunistic infections are not exclusion criteria; 2) CD4 cell count >100 cells/mm3; and, 3) plasma HIV RNA viral load that is undetectable or can be suppressed with antiretroviral treatment. Drug users must abstain from heroin and cocaine, although patients can be in a methadone programme. Accumulated experience in North America and Europe in the last few years indicates that five-year survival in liver recipients coinfected with HIV and HCV is lower than that of HCV-monoinfected recipients, being the five-year survival of around 50%. Conversely, 3-5--year survival of non-HCV-HIV-coinfected liver recipients is very good and it was similar to that of HIV-negative patients. Pharmacokinetic (PK) and pharmacodynamic interactions between NNRTI- or protease-inhibitor based regimens and immunosuppressors have been one of the most important problems in the post-trasplant period, although with the new NNRTI- and protease inhibitor-sparing raltegravir-based regimens we can avoid them. Other problems in the post-transplant period are the high rates of acute rejection, and the HCV re-infection in HIV-infected liver recipients, that is the main cause of mortality. Better anti-HCV management and therapy could improve the long-term outcome of OLT recipients coinfected with HIV and HCV.

Significance of Serum Tumor Markers Carcinoembryonic Antigen, CA 19-9, CA 125, and CA 15-3 in Pre-Orthotopic Liver Transplantation Evaluation

Tumor markers are elevated in a variety of nonneoplastic clinical situations, including liver diseases. Their sensitivity and specificity are lower for tumor screening in these cases. In this study, we investigated the frequency and significance of elevated tumor markers in the pre-orthotopic liver transplantation (OLT) evaluation among patients with end-stage liver disease who did not develop tumors after a long follow-up post-OLT. We performed a retrospective analysis of clinical and biological parameters of 100 OLT candidates comparing data for CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA) levels. CA 125, CA 19-9, CA 15-3, and CEA levels were elevated in 59%, 53%, 29%, and 28% of cases, respectively. CA 125, CA 15-3, and CEA were associated with disease severity (Child-Pugh classification). CA 125 was also elevated among patients with ascites, esophageal varices, or alcohol-related cirrhosis. Elevated CA 19-9 levels were associated with increased CA 15-3 and CEA levels. CA 15-3 levels were also increased among patients with elevated alkaline phosphatase, while elevated CEA was related to ascites, bilirubin, and prothrombin time (PT) levels, as well as alcohol-related cirrhosis. There was no association between hepatocellular carcinoma and tumor markers. In conclusion, CA 125, CA 19-9, CA 15-3, and CEA were frequently elevated among end-stage liver disease patients. These elevations were not associated with tumor diseases in this population.

Intrapulmonary Shunt in the Course of Pediatric Liver Transplantation

The hepatopulmonary syndrome occurs when an intrapulmonary shunt (IPS) causes hypoxemia in patients with cirrhosis. Because IPS has not been clearly defined in children, we investigated the prevalence, clinical characteristics, and outcomes of IPS in children undergoing liver transplantation (OLT). Of the 107 pediatric OLT recipients between December 1994 and March 2005, 18 (16.8%) had IPS, as evaluated by contrast-enhanced echocardiography (CEE) at 9 months to 16 years of age. The degree of IPS was classified into five grades according to the extent of microbubbles in the left ventricle, with significant IPS defined as grade II or higher. Baseline characteristics, including serum total bilirubin, albumin, aminotransferase, and prothrombin time, did not differ in patients with or without IPS. The patients with IPS had significantly lower Pa o 2 and Sa o 2, longer duration of mechanical ventilation and hospital stay, and higher postoperative morbidity and mortality than patients without IPS ( P < .05 each), but there were no other significant differences between the groups. The six patients with significant IPS (one grade II, three grade III, and two grade IV) showed a significantly greater morbidity and mortality than patients with grade I IPS ( P < .05). Most of the positive CEE findings of IPS regressed within 6 months after OLT. These findings indicated that IPS is not uncommon among children undergoing OLT, but is reversible. Because severe IPS may increase patient morbidity and mortality, early assessment of IPS status using CEE is essential for pediatric OLT candidates.

Utilizing generalized autocalibrating partial parallel acquisition (GRAPPA) to achieve high-resolution contrast-enhanced MR angiography of hepatic artery: Initial experience in orthotopic liver transplantation candidates

Objective To evaluate feasibility of using GRAPPA to acquire high-resolution 3D contrast-enhanced MR angiography (CE-MRA) of hepatic artery and value of GRAPPA for displaying vessels anatomy. Materials and methods High-resolution CE-MRA using GRAPPA was performed in 67 orthotopic liver transplantation recipient candidates. Signal intensity (SI) and relative SI, i.e., Cv-ro (vessel-to-liver contrast) of the aorta and the hepatic common artery (HCA), were measured. The SI and the relative SI were compared and analyzed using T-test. For purpose of qualitative evaluation, the vessel visualization quality and the order of depicted hepatic artery branches were evaluated by two radiologists independently and assessed by weighted kappa analysis. The depiction of hepatic arterial anatomy and variations was evaluated, and results were correlated with the findings in surgery. Results The mean SI values were 283.29 ± 65.07 (mean ± S.D.) for aorta and 283.16 ± 64.07 for HCA, respectively. The mean relative SI values were 0.698 ± 0.09 for aorta and 0.696 ± 0.09 for HCA, respectively. Homogeneous enhancement between aorta and HCA was confirmed by statistically insignificant differences ( p-values were 0.89 for mean SI values and 0.12 for mean relative SI values, respectively). The average score for vessel visualization ranged from good to excellent for different artery segments. Overall interobserver agreement in the visualization of different artery segments was excellent (kappa value > 0.80). The distal intrahepatic segmental arteries were well delineated for majority of patients with excellent interobserver agreement. Normal hepatic arterial anatomy was correctly demonstrated in 53 patients, and arterial anomalies were accurately detected on high-resolution MRA image of all 14 patients. Conclusion High-resolution hepatic artery MRA acquired using GRAPPA in a reproducible manner excellently depicts and delineates small vessels and can be routinely used for evaluating OLT candidates.

Characteristics and Outcome of Portopulmonary Hypertension

Purpose: Pulmonary artery (PA) hypertension developing in patients with portal hypertension (PH), also called portopulmonary hypertension (PPHTN), caries significant mortality in patients undergoing liver transplant (OLT). With OLT becoming the standard of care, implications of PPHTN are increasingly recognized. However, PPHTN remaines rather poorly characterized. Aim: To define the clinical, biochemical, homodynamic and outcome characteristics of PPHT. Methods: PPHTN was defined as PA systolic pressure ≥ 40 mm Hg (PAs), PA mean pressure ≥ 25 mm Hg (PAm), Pulmonary capillary wedge pressure (PCW) <15 mm Hg, Pulmonary vascular resistance (PVR) ≥ 120 dynes.s.cm−5. During evaluation of candidates for OLT eleven patients identified to have PPHTN were followed for 19 to 48 months. Their clinical, biochemical, hemodynamic parameters, natural history and outcome were analyzed. Results: There were 8 females and 3 males with age of 51.4 ± 2.3 years. Etiology of liver disease was alcoholism and autoimmune hepatitis in one each, cryptogenic in 2, Primary sclerosing cholangitis in 2 and chronic hepatitis C in 5. Shortness of breath was experienced by one, 9 had ascites, and 6 had significant splanchnic varices. Biochemical parameters revealed MELD score of 13.2 ± 1.0 (range 8–18), total s. bilirubin 2.0 ± 0.3 mg%, s. albumin 3.3 ± 0.2 Gm%, AST 109.4 ± 28.3 IU and ALT 72.4 ± 20.5 IU. Cardiac output was 7.4 ± 0.9 L/min (range 4.6–11.4), PAs was 57.5 ± 4.2 mm Hg, PAm was 33.8 ± 3.7 mm Hg, PCW was 13.5 ± 2.1 mm Hg, PVR was 299.5 dynes.s.cm−5, 2-D echocardiography showed tricuspid regurgitation (TR) in all. Treatment (calcium channel blockers, sildenafils, endothelin receptor antagonists, or intravenous prostacyclin analogue) for 19.4 ± 4.3 months (range 1–48) dropped the PAs to 49.1 ± 4.6 mm Hg. Four patients were given OLT, seven denied OLT because of high PA pressure. From the time diagnosis of PPHTN was made, six are alive for 33.3 ± 4.1 months and 5 died after 17.6 ± 6.3 months. Conclusions: PPHTN occurs in patients with cirrhosis of all etiologies with significant PH and is more frequent in females. PA hypertension remains asymptomatic in most patients. All of the patients have hyperdynamic cardiac hemodynamics and increased PVR. The finding of TR on 2 D echocardiography is a good screening indicator of PA hypertension. Response to treatment is variable and less than desirable. Significant PPHTN often prohibits OLT and those not transplanted have decreased survival.

Management of fulminant hepatic failure in the USA: Results from a survey of 14 liver transplant programs

Acute liver failure (ALF) is an uncommon condition of high mortality requiring urgent diagnosis and facilities for intensive care and liver transplantation (OLT). With few therapeutic trials in the USA, little is known about standard management of ALF. Aims: To assess the therapeutic approach to ALF in USA and to identify accepted and controversial aspects of care. Methods: A questionnaire to assess the management of ALF was completed by the physician representative of each of 14 liver transplant centers participating in the muiticenter Acute Liver Failure Study Group; these centers perform 30% of all liver transplants in USA. Results: The following care is instituted in most centers (# of centers): peptic ulcer prophylaxis, mainly H2 blockers (13); enteral nutrition if tolerated (13); hemostatic monitoring by PT/INR and platelet count (14); FFP (14) and platelets (13) prior to invasive procedure; use of N-acetylcysteine in acetaminophen overdose (13); surveillance cultures of blood and urine (12); elevation of head of bed (11 ); liver biopsy only with clinical suspicion of unusual diagnosis (11). With stages Ill/IV encephalopathy and/or need for mechanical ventilation, therapy includes hemodynamic monitoring by arterial (14), central venous (14) and pulmonary artery catheters (13); intracranial pressure monitoring (ICP) with epidural or subdural catheters in OLT candidates (13); head scanning by CT (14); hyperventilation as first line therapy to treat Cerebral edema (11); mannitol therapy to treat cerebral edema (14); renal dialysis by CWHD (13); and use of King's College criteria for assessment for OLT (13). More controversial areas include use of medical agents for PSE (10), barbiturate coma to treat cerebral edema (10), prophylactic therapy of cerebral edema (6), vitamin K therapy (10), surveillance cultures, use and type of prophylactic antibiotics, blood products to prevent bleeding (4), and nutritional support with TPN (6) or BCAA (4). Conclusions: The patient with ALF requires specialized care in a liver transplant center where aggressive measures intensive hemodynamic, ICP monitoring, use of CWHD are almost universal. Also universal are some less invasive measures (e.g. surveillance cultures, peptic ulcer prophylaxis) which can be instituted early in the referring center prior to transfer. Many areas of supportive care remain controversial and optimal therapy for ALF requires further investigation.

Hypothermia for fulminant hepatic failure: A cool approach to a burning problem

Background Increased intracranial pressure as a complicationof acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. Methods We studied seven consecutivepatients aged 16–48 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32–33°C. Patients who were not suitable candidates for OLT (patients 1–3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37°C. Patients who were suitable candidates for OLT (patients 4–7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. Findings The four patients who were candidates for OLTwere successfully maintained until transplantation with 13 h (range 10–14 h) of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25–49 mm Hg) and was reduced in all patients to 16 (13–17) mm Hg (p < 0.05). Cerebral blood flow decreased from 103 (25–134) ml 100 g −1 mint before cooling to 44 (24–75) ml 100 g −1 min −1 after cooling (p < 0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 mm Hg (37–56) mm Hg to 70 (60–78) mm Hg (p < 0.05) and for cardiac index a decrease from 9.8 (7–13) to 5.1 (4.3–6.1) L per min per m 2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. Interpretation Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure

Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.

CHEMOEMBOLIZATION-INDUCED TUMOR NECROSIS: CORRELATION OF MRI, PATHOLOGY AND CLINICAL OUTCOME IN CIRRHOTICS WITH HEPATOCELLULAR CARCINOMA.

345 Purpose: We set out to determine how well MRI estimates of chemoembolization (CE) - induced tumor necrosis correlate with explant pathology and whether either is a predictor of outcome following OLT and chemo for the treatment of hepatocellular carcinoma (HCC). Methods: MRI is performed in all OLT candidates to estimate liver volume, to detect mass lesions, and to assess portal vein patency. Patients with known HCC undergo CE, OLT, and chemo. Biopsy for diagnosis of HCC was not performed routinely. Following each CE an MRI was done to determine percent necrosis of the targeted tumor(s), change in tumor size, and to check for additional lesions. Following OLT the explanted livers were examined and CE-induced tumor necrosis was quantified. Results: 360 OLT's were performed in 342 patients. CE was performed prior to OLT on 23 patients with known HCC. Three patients were excluded from analysis: two died of sepsis within 30 days of OLT and one patient had persistent disease after OLT. 16/20 patients are alive (median follow-up = 19 months). Six patients had recurrent HCC. MRI and pathologic data were complete for 13 patients with a total of 17 lesions. Pathologically nine tumors demonstrated >80% necrosis. Four tumors showed no necrosis and four demonstrated 20%, 30%, 70%, and 70% necrosis. In addition to necrosis it was noted that chemoembolized tumors were surrounded by a thick fibrous capsule. Estimates of tumor necrosis by MRI were within 10% of their pathologic assessment in 13/17 (76%) lesions. Percent necrosis by MRI and pathology in the 4 lesions that showed poor correlation were, respectively, 31% vs. 100%, 29% vs. 90%, 27% vs. 70%, and 87% vs. 70%. Cumulative adriamycin doses during CE of < 50 mg were used to treat 12 lesions whose mean necrosis was 14% whereas CE doses of >50 mg were used for 23 lesions whose mean necrosis was 74% (p<0.05). The number of CE treatments (1 vs. multiple) and the interval from CE to OLT (within 1 month vs. > 1 month prior to OLT) was not correlated with percent necrosis. There was no correlation between necrosis and clinical outcome. The six patients whose disease recurred had a mean tumor necrosis in 11 lesions of 44%. The fourteen patients who remain disease-free had a mean tumor necrosis in 24 lesions of 58%. Conclusions: The timing and frequency of CE did not have an impact on the degree of tumor necrosis but adriamycin doses > 50 mg administered during CE resulted in significantly more tumor necrosis than doses < 50 mg. MRI estimates of tumor necrosis compared very well with actual necrosis as determined by pathologic examination. There was no correlation between extent of tumor necrosis and recurrence rates. The presence of the fibrous capsule may be critical since the beneficial effect of CE in the treatment of HCC does not correlate with the degree of tumor necrosis induced by CE.

Recurrence of nonalcoholic steatohepatitis following liver transplantation.

Patients with nonalcoholic steatohepatitis (NASH) may develop progressive liver dysfunction necessitating liver transplantation (OLT). We report the incidence of recurrent disease and outcome in patients undergoing OLT for NASH. Patients transplanted for NASH were identified according to pretransplant and explant liver histology. Patients with significant alcohol consumption were excluded. Medical records were reviewed to extract pre- and posttransplant data, including sequential body weight, biochemistry, and graft histology. Of 622 liver explants, eight patients had features consistent with NASH. All patients were female with a median age of 58. Seven patients were diagnosed with NASH preoperatively, including three who had undergone jejunoileal bypass. One patient was diagnosed as cryptogenic cirrhosis. At a median of 15 months following OLT, all of the eight patients were alive with no graft failure. Six patients developed persistent fatty infiltration in their graft, three of whom had accompanying hepatocellular degeneration, consistent with a diagnosis of recurrent NASH. In two patients, transition from mild steatosis to steatohepatitis and early fibrosis was observed over one to two years. The patients who did not develop recurrent steatosis had significant weight loss following transplantation, although the length of follow-up was relatively short. Patients undergoing OLT for NASH may develop recurrent steatosis shortly after transplantation, with possible progression to steatohepatitis and fibrosis. Although longer follow-up is necessary to determine the eventual prognosis related to the recurrent fat and fibrosis in the graft, patients with endstage liver disease due to NASH should be considered good candidates for OLT.