Prognostic models in end stage liver disease.

Cirrhosis is a major cause of death worldwide, and is associated with significant health care costs. Even if milestones have been recently reached in understanding and managing end-stage liver disease (ESLD), the disease course remains somewhat difficult to prognosticate. These difficulties have already been acknowledged already in the past, when scores instead of single parameters have been proposed as valuable tools for short-term prognosis. These standard scores, like Child Turcotte Pugh (CTP) and model for end-stage liver disease (MELD) score, relying on biochemical and clinical parameters, are still widely used in clinical practice to predict short- and medium-term prognosis. The MELD score, which remains an accurate, easy-to-use, objective predictive score, has received significant modifications over time, in order to improve its performance especially in the liver transplant (LT) setting, where it is widely used as prioritization tool. Although many attempts to improve prognostic accuracy have failed because of lack of replicability or poor benefit with the comparator (often the MELD score or its variants), few scores have been recently proposed and validated especially for subgroups of patients with ESLD, as those with acute-on-chronic liver failure. Artificial intelligence will probably help hepatologists in the near future to fill the current gaps in predicting disease course and long-term prognosis of such patients.

Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry).

Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10,943 VIR, 1478 ALD+VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p=0.04, p=0.05). By multivariate analysis, ALD+VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.

Transjugular intrahepatic portosystemic shunt in non-cirrhotic portal hypertension related to cystic fibrosis in a lung transplant patient.

Liver involvement is not uncommon in patients with cystic fibrosis (CF). Even if serious complications as non-cirrhotic portal hypertension, cirrhosis and liver failure rarely occur, they are associated with impaired survival and reduced quality of life. Herein, we have reported the first case of a patient with CF and non-cirrhotic portal hypertension who underwent transjugular intrahepatic portosystemic shunt placement for recurrent variceal bleeding after bilateral lung transplantation, and we have reviewed the available literature pertaining to this field.

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.

HCV histological recurrence and survival following liver transplantation in patients with and without hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatitis C virus (HCV)-related cirrhosis is one of the leading indication for liver transplantation (LT) and a major risk factor for the development of hepatocellular carcinoma (HCC). HCV recurrence after LT is universal. This study evaluated HCV recurrence and survival in patients transplanted for HCV and HCC. METHODS: We evaluated all adults transplanted for HCV cirrhosis between January 1999 and December 2006, HCC was diagnosed on the explant and HCV recurrence confirmed on protocol liver biopsies performed at 6 months and yearly after LT. The sustained viral response (SVR) was defined as HCV-RNA undetectable at 6 months after therapy discontinuation. The patient survival rates were assessed with Kaplan-Meier curves and the chi-square test was used when appropriate. RESULTS: Two hundred sixteen patients underwent LT for HCV including 153 men and 63 women of mean age 54 years with a mean follow-up of 35 months. There were 71 (33%) HCC(+) patients. At 1, 3, and 5 years from LT severe fibrosis (Scheuer 3-4) due to the HCV recurrence was reported in 18%, 14%, and 11% for HCC(+) and 14%, 16%, and 28% for HCC(-) patients respectively (P=NS). HCC recurred only in 3 (4%) patients at a mean follow-up of 3 years. Patients who received antiviral treatment after LT were 10% HCC(+) and 12% HCC(-) patients (P=NS). SVR was seen in 3/7 (43%) of HCC(+) and in 10/18 (55%) of HCC(-) patients (P=NS). At 1, 3, and 5 years the patient survivals was 91%, 86%, and 86% for HCC(+) and 94%, 86%, and 83% for HCC(-) patients, respectively (P=NS). CONCLUSIONS: Severe fibrosis due to HCV recurrence, which increases over time, involves one third of transplanted patients at 5 years after LT. The long-term survival was identical among HCC(+) compared to HCC(-) recipients. The recurrence of HCC was negligible and did not affect patient survival.

The transjugular route: the key hole to the liver world.

Portal hypertensive complications are major causes of morbidity and mortality in patients with liver cirrhosis. The advent of the transjugular route with its minimal access allows non-surgical management of portal hypertension, therapy of venous complications of liver transplantation, monitoring of therapy for portal hypertension, hepatic venous pressure gradient and is also the major route to treat hepatic venous obstruction syndromes. In addition, the transjugular route is a safe route to perform a liver biopsy (transjugular liver biopsy) and allows retrograde evaluation of the portal vein. All these procedures can be combined in the same session. These hepatic interventional radiological skills should be incorporated into the expertise of the liver team in specialised hepatological centres, particularly in liver transplant centres as they are especially useful in improving outcomes of cirrhotic patients on the liver transplantation waiting list. A limitation in achieving this goal, could be the number of experienced radiologists, but hepatologists can be trained, at least for the most simple procedures (transjugular liver biopsy and hepatic venous pressure gradient). This would allow wider applicability and use of these diagnostic and therapeutic techniques, all through a 2 mm hole in the neck--the key hole to the liver world.

The effects of glycosaminoglycans on coagulation: a thromboelastographic study.

Endogenous heparinoids impair coagulation, evidenced by thrombelastography in cirrhotic patients with bacterial infection, but it is not clear which glycosaminoglycans can be detected by native and heparinase-modified thrombelastography. To assess the effects of different glycosaminoglycans on thrombelastography parameters and the reversibility of these effects by heparinase-I-modified thrombelastography. Twenty volunteers were enrolled. Solutions of heparan sulphate, dermatan sulphate, and chondroitin-4-sulphate were prepared at 'equivalent' concentrations, based on the composition and anticoagulant activity of danaparoid. Serial dilutions of each glycosaminoglycan were prepared to achieve 1.0, 0.5, 0.1, and 0.05 U/ml. Native and heparinase-modified thrombelastography, anti-activated factor X activity and heparin cofactor II activity were evaluated at each concentration. A statistically significant heparin-like effect was seen with 1 and 0.5 U/ml heparan sulphate, and 1 and 0.5 U/ml dermatan sulphate, which was completely reversed by heparinase-modified thrombelastography. Anti-activated factor X activity was significantly increased in samples containing heparan and dermatan sulphates. The heparin cofactor II activity decreased with 1.0 and 0.5 U/ml dermatan sulphate and chondroitin-4-sulphate, but not with heparan sulphate. Heparan and dermatan sulphates affect haemostasis when added to whole blood in vitro, detectable by native thrombelastography and completely reversed by heparinase-I-modified thrombelastography. They may therefore be responsible for the heparin-like effect seen by thrombelastography in patients with cirrhosis and bacterial infection.

Veno occlusive disease: update on clinical management.

Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation (STC) and is also seen after solid organ transplantation. The incidence of veno occlusive disease (VOD) after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient > 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic acid, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a transjugular intrahepatic portosystemic shunt (TIPS) can be tried, especially to treat VOD after liver transplantation and when multiorgan failure (MOF) is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure.

The concept of quality of life in organ transplantation.

The goal of organ transplantation is not only to ensure the survival of individuals with end-stage heart, lung, liver, kidney, pancreas, and small bowel diseases, but also to offer patients the health they enjoyed before the disease, achieving a good balance between the functional efficacy of the graft and the patient's psychological and physical integrity. Quality of life (QoL) assessments are used to evaluate the physical, psychological, and social domains of health, seen as distinct areas that are influenced by a person's experiences, beliefs, expectations, and perceptions, and QoL is emerging as a new medical indicator in transplantation medicine too.

Algorithm for prioritization of patients on the waiting list for liver transplantation.

UNLABELLED: Prioritization of patients on the waiting list (WL) for OLT is still a critical issue. Numerous models have been developed to predict mortality before and after OLT. AIM: The aim of the study was to prospectively evaluate cirrhotics with and without hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) severity of liver disease on the WL and at transplant, mortality on the WL and after OLT, and their correlations. MATERIALS AND METHODS: An algorithm based on seven patient variables (MELD, CTP, UNOS, HCC, BMI, waiting time, age) was created by software dedicated to prioritize patients on the waiting list. RESULTS: We evaluated 118 patients including 75 men and 43 women of age range 19 to 66 years, who underwent OLT from July 2004 to June 2006. Mean CTP and MELD at listing were 8.44 (range 6-12) and 13 (range 2-24), respectively. Overall mortality on the WL at 24 months was 13%, which was significantly higher among patients with MELD > 25 compared to patients with MELD 0 to 15 (P < .0001) or MELD 16 to 25 (P = .0007) at listing. Mean MELD at OLT was 15 (range 7-36), which was significantly lower in patients with than without HCC (MELD 12 vs 16; P = .0003). Six hundred-day patient survival was significantly lower among patients with MELD > 25 compared to patients with MELD < 25 at OLT (P = .017), whereas no difference in survival was observed between patients with and without HCC. CONCLUSIONS: The sickest patients are characterized by high mortality both on the waiting list and after liver transplantation. Patients with HCC are transplanted in better condition compared to patients without HCC with the same survival.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

BACKGROUND: Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. AIM: To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. METHODS: We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. RESULTS: We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. CONCLUSIONS: General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

BACKGROUND: Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients. AIMS: To evaluate 6-week mortality in cirrhotic patients admitted to an ICU, and to compare general and liver-specific prognostic scores. METHODS: A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child-Pugh, Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves. RESULTS: Major indication for admission was respiratory failure (35.6%). Median (range) Child-Pugh, APACHE II, MELD and SOFA scores were 11 (5-15), 18 (0-44), 24 (6-40) and 11 (0-21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, > or =3 = 90%), higher FiO(2), lactate, urea and bilirubin; resulting in good discrimination [area under receiver operating characteristic curve (AUC) = 0.83], similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child-Pugh (AUC = 0.78 and 0.72, respectively). CONCLUSIONS: Cirrhotics admitted to ICU with > or =3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child-Pugh scores.

Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with and without cavernous transformation.

BACKGROUND: Treatment options for patients with portal vein thrombosis are limited. AIM: To evaluate the feasibility and efficacy of transjugular intrahepatic portosystemic shunt for portal vein thrombosis with/without cavernomatous transformation. METHODS: A survey of such patients, referred for transjugular intrahepatic portosystemic shunt between 1994 and 2005, was performed. Success rates, complications, transjugular intrahepatic portosystemic shunt patency and clinical progression were examined. RESULTS: Transjugular intrahepatic portosystemic shunt was attempted in 28 patients (13 cirrhotics). Indications were: presurgery/transplantation (2), worsening of ascites (2), variceal bleeding (15 - 8 elective), refractory ascites (3), portal biliopathy (3) and portal vein thrombosis complicating Budd-Chiari syndrome (2). Transjugular intrahepatic portosystemic shunt was placed successfully in 19 of 28 (73%); 23 of 28 had complete portal vein thrombosis and 9 of 23 had cavernous transformation and transjugular intrahepatic portosystemic shunt was successfully placed in six of these. In the 19 patients with transjugular intrahepatic portosystemic shunt, the mean follow-up was 18.1 months (range 5-70): six patients had stent revisions; three had liver transplantation, one died of bleeding. Most cirrhotic patients had an improvement in the Child-Pugh score. In the failed transjugular intrahepatic portosystemic shunt group, two of nine died, and three had further bleeding. CONCLUSIONS: Transjugular intrahepatic portosystemic shunt should be considered for selected patients with symptomatic complete portal vein thrombosis with/without cavernous transformation, as clinical improvement and less rebleeding occur when transjugular intrahepatic portosystemic shunt placement is successful.

New insights into the coagulopathy of liver disease and liver transplantation.

The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

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.

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.

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.

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.