Microvascular autonomic dysfunction may justify false-positive stress myocardial perfusion imaging in patients with liver cirrhosis undergoing liver transplantation.

BACKGROUND: Up to 15% of liver transplant candidates have asymptomatic coronary artery diseases, which increase the risk of cardiac complications during and after transplantation. The aim of this study was to prospectively investigate the usefulness of an integrated cardiological approach in cirrhotic patients undergoing liver transplantation. METHODS: Twenty-four consecutive patients undergoing evaluation for liver transplantation were studied by assessing risk factors for coronary artery diseases, electrocardiogram with QTc interval determination, chest X-ray, echocardiography, 24-hour Holter monitor, myocardial perfusion scintigraphy (99mTc)MIBI-GSPECT at rest and after dipyridamole infusion. Cardiac (123)I-metaiodobenzylguanidine (MIBG) scan and coronarography were performed in patients with myocardial perfusion defects. Twenty three of 24 patients underwent successful liver transplantation; one patient died on the waiting list. RESULTS: Before liver transplantation, 29% of patients were diabetic and 41% were smokers. Eleven of 24 patients had a prolonged QTc interval, and 3/24 had positive myocardioscintigraphy after dipyridamole infusion: in two coronarography was negative, while the (123)I-MIBG washout was altered. No cardiac events were recorded during the short-and long-term follow-up after surgery. CONCLUSIONS: Predictive value of positive cardiac (99mTc)MIBI-GSPECT in patients with liver cirrhosis is low, and this may be due to alterations of cardiac microvascular tone as showed by cardiac (123)I-MIBG scan.

Neuropsychological and neurophysiological evaluation in cirrhotic patients with minimal hepatic encephalopathy undergoing liver transplantation.

BACKGROUND: Cirrhotic patients without overt hepatic encephalopathy may have cerebral function alterations called minimal hepatic encephalopathy (MHE). Our goal was to evaluate the role of partial pressure of ammonia (pNH3), neuropsychological, and neurophysiological assessment in detecting cognitive changes in cirrhotic patients awaiting liver transplantation. MATERIALS AND METHODS: Fourteen cirrhotic patients listed for liver transplant were studied. All patients underwent the neuropsychological battery called PSE. Neurophysiological assessment including spectral EEG (sEEG), evoked potential P300 and pNH3 and venous and arterial ammonia levels was performed in all patients. Four patients were transplanted. RESULTS: Liver disease etiology was alcoholic in four patients, viral in six mixed in two, and cryptogenic in two. PSE scores revealed MHE in 8 patients; sEEG was altered in 6, and P300 in 1. No correlations were detected between P300, sEEG, and PSE. pNH3 and arterial ammonia levels were significantly higher in the subgroup of patients with altered sEEG and were correlated with theta band increase in sEEG but not with pathological PSE scores or P300 wave abnormalities. CONCLUSIONS: The combination of sEEG and PSE, and possibly also pNH3 and arterial ammonia, is useful in detecting cerebral function alterations in cirrhotic patients with no apparent encephalopathy, whereas P300 is not. The diagnosis of MHE obtained using the multimodal approach adopted in this study may enable the adequate treatment of these patients prior to surgery, which includes advising them not to drive and adjusting their priority on the waiting list for OLTx in the light of a condition that cannot be evaluated by Child Pugh score and MELD score.

Does liver-disease aetiology have a role in cerebral blood-flow alterations in liver cirrhosis?

BACKGROUND: Studies using brain-imaging techniques have shown changes in regional blood flow (rCBF) in patients with liver cirrhosis. It remains unknown whether the aetiology of liver disease accounts for these changes. AIMS: To evaluate whether the aetiology of liver cirrhosis is associated with different patterns of rCBF. MATERIALS AND METHODS: A total of 50 patients with end-stage liver disease and no overt encephalopathy were studied. Thirteen age-matched subjects admitted to the neurology department for headache were used as controls. Exclusion criteria were focal brain lesions, severe brain atrophy and any abnormalities found on computed tomography scan suggesting other central nervous system diseases, alcohol intake or use of neuroactive drugs for at least 6 months. rCBF was assessed using single-positron-emission tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HM-PAO) as a tracer in all patients and controls. The Mann-Whitney U test was used for statistical analysis. RESULTS: The liver-disease aetiology was as follows: alcoholic (A) in 19 patients; viral (V) (hepatitis B virus, hepatitis D virus, hepatitis C virus) in 14 patients; alcoholic with concomitant viral (A + V) in five patients; and cholestatic (C) (primary biliary cirrhosis, primary sclerosing cholangitis) in 12 patients. SPECT showed significantly lower rCBF in cirrhotic patients than in controls for most cortical and subcortical regions and in alcoholic and viral patients than in cholestatic liver disease patients for some cortical regions. When patients were grouped according to previous alcohol abuse (including cases with a concomitant viral aetiology), rCBF was significantly lower in the frontal superior, medial and temporal inferior regions in the alcoholic group. CONCLUSIONS: Cerebral blood flow is significantly lower in patients with liver cirrhosis than in controls and, among cirrhotics, it is lower in alcoholic and viral cirrhosis than in cholestatic liver disease. In patients with previous alcohol abuse, cerebral blood flow was significantly more reduced in the frontal and temporal regions compared with patients without previous alcohol abuse.

Liver transplantation for the management of hepatoblastoma.

INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. RESULTS: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

Adjuvant chemotherapy for transplanted hepatocellular carcinoma patients: impact on survival or HCV recurrence timing.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. In the Western world the current epidemic of cirrhosis due to the hepatitis C virus (HCV) is increasing the number of new cases. Liver transplantation (OLTx) represents a radical treatment for HCC and the underlying cirrhosis. Whether adjuvant chemotherapy is indicated in the postoperative period to prevent recurrence is controversial. MATERIAL AND PATIENTS: Forty-eight HCC patients underwent liver transplantation during 11 years, including 21 who were chemo-treated (CT) patients. Thirty-one patients (65%) had post-necrotic virus-C cirrhosis (PNC-C). Twenty-one cases (44%) were p-TNM stages III-IV, and 15 cases (31%) incidental HCC detected in the explanted liver. Seven HCV patients (15%) received chemotherapy (before 1998). RESULTS: One-, 3-, and 5-year overall survival rates were 100%, 85%, 79% (CT group), and 89%, 71%, 71% (no CT group), respectively. The HCV recurrence-free survival rates at 3, 6, and 12 months were 29%, 14%, 0% for the CT group, versus 76%, 38%, 25% for the no CT group (P =.005). CONCLUSIONS: Discontinuation of HCV-HCC patients by chemotherapeutic adjuvant protocols after transplantation appears rational due to the early hepatitis C recurrence confirmed in our series. Moreover, few studies have demonstrated that CT prolongs survival of HCC transplanted patients. New pharmacological approaches are necessary to solve these questions.

Extreme marginal donor: severe hypothermia as a rare preservation condition for explantable organs--a case report.

UNLABELLED: The progressive increase in patients with end stage liver disease has lengthend the waiting- list for liver transplantation. Unfortunately this has not been followed by a suitable increase in the number of donors. The expanding "donor pool" has required use of "marginal" donors (ICU stay > 10 days, sepsi; steatosis > 30-40%, hypernatremia > 155 mmol/L, inotropic drugs). We report the case of a skier who remained for more than 1 hour in cardio-respiratory arrest under the snow; the 49-year-old women was extracted from the snow after 1 hour and 12 minutes and found to be asystolic, fixed pupils and deep hypothermia (27.2 degrees C). After cardiopulmonary resuscitation, partial cardio-respiratory activity was re-established. In the ICU severe hypothermia (26.7 degrees C) was treated with extracorporeal circulation until a re-establishment of satisfactory cardio-circulatory conditions was obtained. Unfortunately cerebral anoxic cerebral death was established and multiorgan procurement performed 3 days later. After liver transplantation into a 59 year-old patient with PNC-C was performed. The course was uneventful and the patient was discharged on the 19th postoperative day. CONCLUSIONS: Organ procurement from donors involved in accidental traumatic events with cardio-respiratory arrest and hypothermia, is similar to the non-heart-beating donor (NHBD) condition. Correct cardiopulmonary resuscitation and the use of extracorporeal circulation for gradual restoration of body temperature are necessary for optimal organ perfusion. In the present case the anoxic insult induced by the cessation of the cardio-respiratory function, was probably mitigated (if not even annulled) by the hypothermia.

Functional and morphological graft monitoring after liver transplantation.

The development of effective immunosuppressive drugs and the refinement of surgical procedures have led to remarkable improvements in the long-term success of liver transplantation. This procedure is now widely recognised as an effective, preferable therapeutic option for the treatment of end-stage liver disease. The early diagnosis of dysfunction is an indispensable tool for the successful management of the hepatic allograft recipient. Liver function is usually assessed by biochemical and morphological examinations, usually based on coagulation factors (fibrinogen, fibrinogen degradation peptide, factor V, prothrombin time and prolonged thromboplastin time), transaminases, gamma-GT, ALP, bilirubin and lactic acid, and histology. Liver biopsy is usually performed before the implantation of the graft to assess the viability of the liver and following liver transplantation, whenever clinical events warrant it or as part of a routine biopsy schedule.

GH/IGF system, cirrhosis and liver transplantation.

The GH-related effects are primarily mediated by insulin-like growth factor I (IGF-I), a peptide hormone almost completely produced by the liver. Liver cirrhosis is usually accompanied by a fall in protein turnover. Furthermore, an important consequence of chronic liver disease (CLD) is growth hormone/insulin-like growth factor (GH/IGF) axis modification and growth failure. Nutritional status also suffers in this condition, and IGF-I has been proposed as a marker of hepatocellular dysfunction, malnutrition and survival. CLD is characterised by alterations of various clinical biochemistry laboratory parameters. Aminotransferases, bilirubin, plasma proteins, together with prothrombin time and gamma globulins, are usually examined for laboratory diagnostic and/or monitoring purposes. These traditional parameters are also used in the perioperative liver transplantation, but an early signal of graft functioning has still not been established. The aim of the present work is a review of the possibility offered by the clinical biochemistry laboratory GH/IGF investigation in the outcome of liver transplantation.

Physiological and clinical implications of proANP(1-98) circulating levels in the perioperative phase of liver transplantation.

BACKGROUND: ProANP(1-126), the prohormone synthesized and secreted by atrial myocites, generates an ANP peptide family, the main forms of which are proANP(1-30), proANP(31-67), proANP(1-98) and proANP(99-126). These molecular circulating forms are involved in hemodynamic and electrolyte homeostasis. In cirrhotic patients, volume homeostasis is almost impaired due to abnormal sodium retention, which results in ascites formation and hemodynamic changes, including high cardiac output and low systemic vascular resistance. During liver transplantation, in the anhepatic phase, hemodynamic instability may occur because of decreased venous return due to surgical manipulation of inferior vena cava, considerable blood loss or cross-clamping. Moreover, marked hemodynamic instability is often observed at the reperfusion of the graft. AIMS: The aims of present study are to investigate the changes of ANP during the perioperative phases of Orthotopic Liver Transplantation (OLTx) in end-stage cirrhotic patients. PATIENTS AND METHODS: From July to September 1999, 11 cirrhotic patients undergoing to OLTx were included in the study: seven males and four females (average age 46+/-10.4 years) affected by post-alcoholic cirrhosis [Hypertension 15 (1990) 9], post-hepatitis cirrhosis [D.G. Gardner, M.C. Lapointe, B. Kovacic-Milivojevic, C.F. Deschepper, Molecular analisys and regulation of the atrial natriuretic factor gene, in: A.D. Struphers (Ed.), Frontiers in Farmacology and Therapeutics: Atrial Natriuretic Factor, Blackwell, Oxford, England, 1991, pp. 1-22], Wilson disease [Life Sci. 28 (1981) 89] and polycystic disease [Life Sci. 28 (1981) 89], autoimmune cirrhosis [Life Sci. 28 (1981) 89]. In each patient, a hemodynamic assessment was achieved using a Swan-Ganz catheter. Periferical venous samples were performed during and immediately after OLTx for the determination of ANP(1-98) and other biohumoral parameters. RESULTS: Mean ANP(1-98) (pmol/ml mean+/-SD) basal levels resulted higher than that recorded in the group of healthy subjects. A significant correlation between 24-h post-reperfusion ANP and intra-operative RBC and RIS requirement was found (p<0.05). The basal values resulted significantly higher than that observed at phase II degrees (p<0.04) and lower than that at phase VI degrees (p<0.05); the anesthetic induction values were significantly lower than that observed at phase VI degrees (p<0.03). CONCLUSIONS: ANP(1-98) values may represent a useful marker of hemodynamic derangements during and after OLTx. Further clinical correlations will need a larger patient basis.

Liver transplantation. A summary of our surgical practice.

At the turn of the new century, liver transplant procedures can finally be considered an efficient treatment option. Technology has helped transplant intervention become a preferred treatment for patients with progressive and irreversible liver failure. New immuno-suppressive drugs have been introduced which reduce the patient's immunological reaction to the implanted organ, entail minimal side effects and improve practical applications of liver transplantation. As a result of these technological advanced and proper disease management, liver transplant procedures are no longer thought of as an elite therapy, reserved for selected patients with end stage liver disease. In our opinion, it is now a sound and valid surgical option with strictly defined characteristics, indications and well-understood limits. Throughout the past decade, we have studied and applied this type of intervention and have come to terms with its rapid expansion at both the theoretical and practical levels. The most significant obstacle remaining today is the discrepancy between the ever increasing demand and limited supply of organs. The future of liver transplant lies in overcoming this obstacle. Liver transplant practice began at our Institute on 23 November 1990 with the first surgical intervention to replace an organ. In the past 10 years, we have exceeded 200 liver transplant procedures.