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Background: Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital., Aims: Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites., Methods: The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached., Results: The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service., Conclusions: For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

The present study, performed in the Department of Internal Medicine and Gastroenterology of Policlinico of Modena, shows the results of the treatment with percutaneous ethanol injection of cirrhotic patients with hepatocellular carcinoma. In the period between June 1991-May 1998, 37 nodules of hepatocellular carcinoma, in 26 cirrhotic patients, were treated with ethanol injection under the ecographic guidance; the total number of sessions was 179. Ten lesions were recurrences (local or distant) in patients already treated. These patients were excluded from surgical treatment because of the high age, the high surgical risk or patient's choice. "Therapeutic success", defined as radiologic (TC or RM) demonstration of complete necrosis at the end of the first cycle of treatment, was achieved in 22/27 nodules after the first treatment (81.5%). Therapeutic success of the recurrence (second treatment) was achieved in 7/10 nodules (70%). In treated patients, survival probability (obtained with Kaplan Meier method) was 84.5%, 73.0%, 50.0%, 38.5%, 26.9%, respectively at 1st, 2nd, 3rd, 4th and 5th year. After a total number of 179 sessions, there were no relevant complications. The results obtained in our experience prove the efficacy and safety of this therapeutic technique in patients with cirrhosis and hepatocellular carcinoma.

Upper gastrointestinal bleeding is a leading cause of death in patients with liver cirrhosis. In most cases haemorrhage originates from oesophageal varices or from congestive gastropathy, and the evaluation of the bleeding risk is based on oesophagogastroduodenoscopic data. The aim of this prospective study was to determine whether the measurement of portal flow velocity by Duplex-Doppler, compared with endoscopic data, can help in detecting patients with cirrhosis at risk of bleeding. One hundred and seventy-three patients underwent endoscopy to ascertain the size of the varices and the severity of congestive gastropathy. For each patient maximal portal flow velocity measurements were obtained. No difference in portal flow velocity was observed between patients with or without oesophageal varices or congestive gastropathy. During a 2-year observation period, 27 patients (15.6%) had at least one episode of acute digestive bleeding. Stepwise multiple logistic regression analysis demonstrated a correlation between oesophageal varices and congestive gastropathy endoscopic grading and the incidence of bleeding; only the former was entered into the final regression equation (p < 0.001). No relationship between the max portal flow velocity value and incidence of bleeding was found. This study shows that portal flow velocity is unrelated to the degree of the endoscopic abnormalities in patients with liver cirrhosis and that it has no value in the identification of patients with cirrhosis at risk of upper gastrointestinal bleeding.

Spontaneous bacterial perionitis (SBP) is a relatively frequent complication of liver cirrhosis and is associated with a high mortality if not early recognized and immediately treated. The text-books of Medicine available in Italy suggest the use of traditional laboratory tests (gravity, total protein concentration, Rivalta's test) to whom add white blood cell count for the assessment of the nature transudative (not infected) or exudative (infected) of ascitic fluid; nevertheless, in every day clinical practice, the association between total protein concentration and type of ascitic fluid may be misleading with respect to the diagnosis of SPB. The aim of this retrospective study, undertaken on 86 patients with liver cirrhosis consecutively admitted and separated in two groups, one without and the other with PSB (white blood cell count > 500/mm3), was to identify criteria for diagnosis of PSB. The traditional laboratory tests were significantly different in the two groups but Rivalta's test. Yet, none of them showed a diagnostic measurement sufficient for the use in the diagnosis of PSB (positive predittive value: gravity 41%, Rivalta's test 36%, total protein concentration 40%). The results of this work show the traditional laboratory tests unable to define the nature of the ascitic fluid. For the diagnosis of PSB the only reliable parameter is the white blood cell count.

Background: Patients with liver cirrhosis and large oesophageal varices run a high risk of digestive haemorrhage due to the rupture of oesophageal varices, an event associated with a high mortality. At present, the only treatment for the prevention of first bleeding from oesophageal varices on which there is general agreement is drug-based. In order to tailor drug treatment to the requirements of individual patients more precisely, an ever-increasing number of drugs is being investigated., Design: Double-blind cross-over study., Methods: Sixteen cirrhotic patients with large oesophageal varices were studied by means of duplex-Doppler ultrasonography to determine variations in portal haemodynamics after oral administration of 0.150 mg clonidine and to compare these with the variations observed after oral administration of 40 mg propranolol., Results: Propranolol caused a significant reduction in maximum portal flow velocity (P < 0.001), whereas clonidine failed to cause any such variation (P = 0.194). Considering as responders those patients who exhibited at least a 10% decrease in maximum portal flow velocity, 11 patients responded to propranolol; of these, three also responded to clonidine. No patient responded only to clonidine., Conclusion: The absence of any effects on the parameters of portal haemodynamics would appear to deny clonidine any significant role in preventing first bleeding resulting from the rupture of oesophageal varices.

In about 50% of patients with liver cirrhosis, upper digestive bleeding is not due to oesaphageal varices rupture, but to a group of peculiar mucosal lesions usually referred as "congestive gastropathy" and "hepatogenic ulcer". The pathogenesis of such mucosal damage is still unclear: an important causative role is commonly thought to be played by portal hypertension, but the role of peptical pathway and of the mucosal barrier impairment must not be underscored as well. Aim of this study was to evaluate the effect of roxatidine in the long-term treatment of mucosal damage in 19 patients with liver cirrhosis. Patients showed a good tolerance and no side effects. The improvement of endoscopic pattern after a three months period of roxatidine therapy was statistically significant; moreover there was no occurrence of digestive bleeding. In conclusion, H2 antagonist may be considered as the drug of choice for the treatment of mucosal damage in patients with liver cirrhosis, for both its safety and effectiveness.

The coagulation parameters of fourteen patients with advanced liver cirrhosis (3 in Child class B and 11 in class C) were prospectively determined quarterly for one year in order to evaluate the possible relationship between high D-dimer levels and incidence of disseminated intravascular coagulation (DIC) and of gastrointestinal bleeding. The values of D-dimer, fibrin(ogen) degradation products, platelets, fibrinogen, prothrombin activity and antithrombin III were fairly stable in almost all patients and no patient developed an overt DIC; one patient had a significant increase in D-dimer three months after the first control. During the one year follow-up, four patients died, one by the occurrence of hepatocellular carcinoma and three by digestive bleeding. Overall, four patients had upper digestive tract bleeding, three from esophageal varices and one from hemorrhagic gastritis. Hemorrhage was more frequent in patients with high D-dimer levels (3/7, 43%) than in patients with normal D-dimer levels (1/7, 14%). In conclusion, the detection of high D-dimer levels in patients with advanced cirrhosis is not predictive for the occurrence of a overt DIC but seems to be related with an increased risk of gastrointestinal bleeding.

The cases of two patients with liver cirrhosis HCV-related, admitted in our Department in consequence of the development of ascites, anemia and clinical deterioration, are reported. Both patients had all major risk factors for hepatocellular carcinoma and anamnestic and physical findings suggesting this diagnosis; nevertheless, the alpha-1-fetoprotein serum levels and the ultrasonographic findings were not diagnostic for primary hepatic neoplasm. Explorative paracentesis was diagnostic, demonstrating the presence of hemoperitoneum (the hematocrit ratio in the ascitic fluid was 12 and 10, respectively). Magnetic resonance revealed extensive diffuse hepatocellular carcinoma on both cases. Hemoperitoneum, in patients with liver cirrhosis, in face of non diagnostic levels of alpha-1-fetoprotein and ultrasonographic findings, can be indicative of the spontaneous rupture of a diffuse type of hepatocellular carcinoma.

Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro-duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal pain and diarrhea and stopped treatment. Three months later, a new endoscopy was performed in the 11 patients that completed the study (3 patients were lost at follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6 patients (55%), with complete absence of mucosal lesions in 2 patients (P = 0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had digestive bleeding during treatment. Digestive bleeding is a common complication of liver cirrhosis, originating in about 50% of cases from gastro-duodenal mucosal damage. Misoprostol suggests itself as a possible alternative therapy to the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but individual intolerance is frequent and must be preliminary excluded.

Objectives: The aim of this prospective study was to identify the combination of parameters best able to predict the diagnosis of compensated cirrhosis., Methods: One hundred and fourteen patients with suspected chronic compensated liver disease were divided, on the basis of bioptical findings, into two groups: group A, without cirrhosis (n = 58) and group B, with cirrhosis (n = 56). A number of biochemical parameters, the extent of oesophageal varices, spleen size, portal vein diameter and maximum and mean portal flow velocity measured by duplex-Doppler ultrasonography were taken into account in a binary forward-stepwise multiple logistic regression analysis., Results: Only three variables were present in the final regression equation, maximum portal flow velocity affording the highest correlation with the histological diagnosis of cirrhosis (p = 0.0007), with an overall predictive value of 87.7%. When associated with the bipolar diameter of the spleen (p = 0.0169) and the number of platelets (p = 0.0487), the predictive value rose to 94.7%. If all three parameters were normal, a non-cirrhotic liver disease was most likely (96% probability); if two or three of the parameters were abnormal, liver cirrhosis was almost certain (98% probability); if only one parameter was abnormal, the clinical diagnosis was uncertain., Conclusions: This study emphasizes the usefulness of duplex Doppler ultrasonography in the non-invasive diagnosis of compensated cirrhosis.

Portal venous flow velocity (PFV) was measured with duplex-Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non-cirrhotic liver disease in 58 cases (CH-patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC-patients). The normal subjects and the CH-patients had similar values of max-PFV and mean-PFV (max-PFV 26.7 +/- 3.2 and 25.7 +/- 3.4 cm/s respectively; mean-PFV 22.9 +/- 2.8 and 22.4 +/- 3.8 cm/s respectively). The LC-patients' values (max-PFV 19.3 +/- 3.5; mean-PFV 16.9 +/- 2.9) were significantly lower than those of the normal subjects (P less than 0.001) and of the CH-patients (P less than 0.001). Considering the normal max-PFV to be in the range 20-33.1 cm/s (mean +/- 2 s.d. of the normal subjects, 95% confidence limits), max-PFV was reduced in 0/50 normal subjects, 1/58 CH-patients and 39/59 LC-patients (66.1% sensitivity; 98.2% specificity). In conclusion, the duplex-Doppler measurement of PFV is of great interest in the diagnostic study of patients with suspected chronic compensated liver disease and in the early diagnosis of cirrhosis. A low max-PFV is a reliable pointer to liver cirrhosis, whereas a normal max-PFV indicates a non-cirrhotic liver disease but is less probative. Each centre should standardize normal PFV values in order to establish their own threshold value for diagnosing liver cirrhosis.

Sixteen patients (15 males, aged 48-70) affected by liver cirrhosis and oesophageal varices were subjected to duplex-Doppler ultrasonographic study (DDUS). Four patients (three with a portal thrombosis and one with a hepatofugal portal flow) were excluded from the subsequent pharmacological test. The twelve remaining patients took part in a double blind cross-over study that evaluated the variations of heart rate (HR), mean systemic arterial pressure (SAP), portal vein diameter (PVD), maximal and mean portal flow velocity (PFV) after the administration of either 40 mg of propranolol or placebo per os, on two consecutive days. Propranolol caused no significant variation in mean SAP and in PVD, whereas it reduced the HR from 67.7 +/- 8.0 to 58.4 +/- 7.0 beats/min (mean +/- s.d.; P less than 0.001); the maxPFV dropped from 18.2 +/- 5.4 to 14.0 +/- 3.7 cm/s (P less than 0.001) and the meanPFV dropped from 15.3 +/- 4.1 to 13.2 +/- 3.1 cm/s (P less than 0.005). No significant variation was observed with placebo. After propranolol administration eight patients exhibited a significant maxPFV decrease, whereas the other four patients exhibited only a drop in HR, suggesting either drug inefficacy, inappropriate dosage or inadequate duration of treatment. DDUS is the only non-invasive method for the examination of the portal vein system.(ABSTRACT TRUNCATED AT 250 WORDS)

Two liver cirrhosis (LC) patients with all major risk factors for hepatocellular carcinoma (HCC) had, at presentation, serum alfa-fetoprotein levels (AFP) higher than 500 ng/ml, usually considered diagnostic for HCC. They had elevated serum ALT levels too. No neoplastic liver lesions were detected by imaging techniques in both cases. During the following three months we noted a progressive improvement of clinical conditions with contextual normalization of AFP and ALT values. Therefore we suggest, when AFP is strongly elevated in LC patients but no hepatic lesion is detectable, a check for AFP and ALT time-course, before diagnosis HCC.

Immunoglobulin (Ig) serum levels have been assayed in 729 patients with liver cirrhosis of different etiologies, in order to evaluate their prognostic value. Serum levels of three classes of Ig resulted mainly elevated in the three etiological groups (post-hepatitic, post-alcoholic, cryptogenetic) and they were significantly related to the severity of the liver disease, evaluated according to the Child-Turcotte score. The computerized analysis of the survival curves of patients with IgG, IgM, IgA values normal or elevated demonstrated an adverse prognostic rate in those with elevated Ig values. The difference among the survival curves, compared by the Lee-Desu method, was statistically significant (p less than 0.001). Our data suggest that the Ig levels can be considered as a prognostic index in liver cirrhosis patients.

In Italy the incidence of hepatocellular-carcinoma (HCC) in patients with liver cirrhosis is estimated approximately 5% per year. The new imaging technologies make it possible to perform screening programs for the early detection of HCC in these patients; early diagnosis of HCC is recommended as the best strategy in order to enable surgical approach, which seems to be the only effective therapy: screening programs must consider the cost-benefit ratio in the choice of patients and standards of investigation. In the Japanese authors' opinion all patients with liver cirrhosis must be screened every three months with an ultrasonographic liver examination (US) and a measurement of serum alpha-1-fetoprotein level (AFP) and every nine months with a computed tomography (CT) of the liver: at a 5% annual incidence of HCC the cost of a single diagnosis is estimated about 8000 +. In our opinion the cirrhotic patients in Child's C class (approximately 20%) can be excluded from the screening programs, since the survival expectation of these patients is always poor, whether HCC is present or not. Furthermore, considering the acknowledged reliability of the US in the detection of space occupying lesions of the liver, periodical CT examination seems to be unproductive. AFP has a low sensibility as a marker of HCC; nevertheless a progressive increase of its levels can be considered an index of possible blastomatous transformation of cirrhotic liver. In comparison with the Japanese screening programs, the proposed changes might obtain a 55% reduction of the cost of a single diagnosis of HCC, without significant diagnostic loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain magnetic resonance (MR) was performed in 29 liver cirrhosis patients without (N = 10) and with hepatic encephalopathy (HE) of chronic recurrent (N = 10) and of chronic persistent (N = 9) type. Sixty percent of the patients with chronic recurrent HE and 100% of the patients with chronic persistent HE showed a bilateral and symmetrical hyperintensity of the globus pallidus in the T1-weighted images while the T2-weighted images were normal, suggesting the possibility of the accumulation of a paramagnetic compound in this brain area during HE. Other findings of the study were evidence of brain atrophy of mild or moderate degree in 70% of patients with chronic recurrent HE and in 77% with chronic persistent HE and patients with liver cirrhosis without HE appeared normal on MR examination.

In patients with liver cirrhosis, especially in the advanced stage, the coexistence of low clotting factor levels, hypofibrinogenemia, thrombocytopenia and elevated fibrin(ogen) degradation product (FDP) and D-dimer levels may suggest the presence of disseminated intravascular coagulation (DIC). In this study we evaluated, in 21 patients with decompensated liver cirrhosis and elevated FDP and D-dimer levels, the time sequence of their coagulation data during a follow-up period of 15 days after the first observation; our aim was to clarify if these patients tend to develop during this time interval a severe consumption coagulopathy as an expression of overt DIC. We evaluated serum fibrinogen, platelet count, prothrombin activity, serum FDP and plasma D-dimer levels at days 1, 3, 6, 10 and 15. The coagulation data were fairly stable during the study period in all patients, even in the two patients who had upper digestive tract bleeding during the study time. Only two patients affected by infectious diseases showed a decrease of D-dimer and FDP levels after healing. Our data suggest that in decompensated liver cirrhosis the detection of elevated FDP and D-dimer levels is seldom related to the occurrence of an overt DIC, at least during a short time interval; in this condition heparin therapy seems therefore not advisable and even potentially dangerous.

Unlabelled: Serum levels of gammaglobulins were evaluated in a population of 1334 patients with liver cirrhosis (mean age +/- SD 54.8 +/- 10.9; 898 males). Hypergammaglobulinemia was not as frequently observed as described in the literature 278 patients (20.8%) had gammaglobulin levels lower than 1.5 g/dl (first group) and the other 1056 had more than 1.5 g/dl of gammaglobulins (second group). At analysis of survival curves the first group had a median survival time of over 60 months, significantly higher than the 37.6 months of the other patients, when compared with the Lee-Desu statistic (p less than 0.01). Moreover, the patients of the first group had a lower incidence of ascites as compared to the second group (28% versus 45%; p less than 0.001), hepatic encephalopathy (7% versus 14%; p less than 0.01) and hepatocellular carcinoma (5.7% versus 8.4%; n.s.). The presence and the degree of oesophageal varices were significantly lower in the patients of the first group than in the others (p less than 0.001); a number of laboratory tests for the evaluation of liver cell function and the Child class distribution were more favourable in the first group than in that of hypergammaglobulinemic patients., In Conclusion: normal blood gamma globulin level is not uncommon in liver cirrhosis and it may be considered a positive prognostic factor, which identifies a group of patients with a better quality of life, a lower incidence of decompensation symptoms and a longer survival time.

Glucose intolerance often occurs in liver cirrhosis; therefore a long-term control of plasma glucose levels appears to be important. For this purpose glycated hemoglobin A (HbA1c) determination is proposed as a suitable method, while no data are available on fructosamine test. In 98 cirrhotic patients serum fructosamine and HbA1c levels were compared with those of normal controls and among cirrhotic patients grouped in non glucose-intolerant and with non insulin-dependent (NIDDM) or insulin-dependent diabetes mellitus (IDDM). The mean HbA1c values of cirrhotic patients with normal glycemic control were significantly lower than normal, and only a few IDDM and NIDDM cirrhotic patients showed high values of HbA1c, indicating that HbA1c is often underestimated in these patients. On the contrary, serum fructosamine levels were on the average higher than normal in nondiabetic patients, but they were significantly higher in IDDM and NIDDM patients than in nondiabetics, and the 72% of NIDDM and 85% of IDDM patients had fructosamine levels higher than the upper normal value. In conclusion, in diabetic patients with liver cirrhosis fructosamine seems to be a more suitable test than HbA1c for monitoring blood glucose levels.

Laboratory diagnosis of disseminated intravascular coagulation (DIC) in liver cirrhosis (LC) could be complicated by the presence of the usual decrement of the hemocoagulative parameters and of an increase of the fibrinogen/fibrin degradation products (FDP). The D-dimer test, more sensible than the one for FDP and specific for the cross-linked fibrin degradation products is now available. A significant difference between the two tests, assayed simultaneously has been demonstrated in 217 LC patients, without any recent or present hemorrhagic signs. The D-dimer was increased in only 60 of the 108 patients with high values of FDP; therefore this test has a screening value higher than FDP. If only the D-dimer is elevated, the FDP assay is indicated: if FDP are normal a thrombosis may be present and, finally, if the FDP are also increased with a concomitant decrement of fibrinogenemia, the laboratory diagnosis of DIC is reasonably certain.

Fibrin(ogen) degradation product (FDP) and D-dimer levels were evaluated in 168 liver cirrhosis (LC) patients without evidence of bleeding. Eighty-two (48%) had FDP higher than 10 micrograms/ml; only 43 of them had a concomitant increase of D-dimer. These alterations were more frequent in older and decompensated patients and correlated to the Child-Turcotte score. In the patients with elevated FDP and/or D-dimer levels the mean values of platelets, prothrombin activity and fibrinogen were not significantly different from those of the other patients and remained fairly stable over the period of the study. Finally, an increase of FDP is frequent in LC and this may suggest a diagnosis of disseminated intravascular coagulation (DIC), but a concomitant increase of D-dimer is rarely detectable, thus excluding this diagnosis. Moreover, even in the cases with increased levels of D-dimer the presence of clinical or laboratory evidence of a consumption coagulopathy, expression of a manifest DIC, seems to be unusual.

The recent development of the duplex-Doppler technique, which combined real-time US with pulsed Doppler flowmetry, has allowed the flowmetric hemodynamic study of large abdominal vessels. As yet, however, both accuracy and possible applications of this method in the study of portal hypertension have not been fully investigated. This study was aimed at assessing whether or not the combined use of Doppler flowmetry and bidimensional US is able to detect portal hypertension in patients with liver cirrhosis (LC), and could therefore represent a valid alternative to endoscopic, angiographic, and direct pressure measurement techniques. Twenty-six patients with LC and 25 control patients were studied with a strictly standardized method; portal hypertension was detected in the patients with LC by EGDS and laparoscopy. The results demonstrated pulsed duplex-Doppler US to be able to detect portal hypertension in 92.4% of LC patients, with 2 false negatives only (7.6%). The difference in the flowmetric data of normal and LC patients was highly significant (p less than 0.001 Student's t test). In conclusion, duplex-Doppler US can be considered as a valid technique to detect portal hypertension in LC patients, and can thus be used as an alternative to more invasive techniques of general use in clinics.

The metabolic effects of selected and branched-chain amino acid (BCAA)-enriched parenteral solutions were studied in liver cirrhosis. After 3 days of an oral protein-free diet with balanced amino acid (AA) infusion, 36 cirrhotic patients without encephalopathy were randomly divided into four groups. Groups A and B were infused for 5 days with BCAA (valine, leucine, isoleucine) at doses of 0.5 and 1.0 g/kg/day, respectively, as the only nitrogen source. Group C received 0.8 g/kg of essential and nonessential AA solution with a prevalence of BCAA; the last group (D) continued the basic standard diet, as control. Routine chemistry, urinary nitrogen losses, nitrogen balance, and the whole plasma AA pattern were detected before and after the treatment period. BCAA alone led to an impressive and significant improvement in the basic AA pattern in both the A and B groups. The same results were obtained in group C for plasma AA. In particular, the ratio of BCAA to aromatic amino acids in groups A, B, and C was significantly increased (p less than 0.01, less than 0.02, less than 0.02, respectively). In group D the AA pattern and the BCAA/aromatic amino acid ratio remained unchanged. The negative nitrogen balance of the base state remained unchanged after 0.5 g of BCAA (A); it improved significantly and became positive during and after the infusions of a double dose of BCAA (B), as it did in the case of selective solutions (C), although to a lesser extent; the negative nitrogen balance of the control group showed only a slight improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

107 (8.2%) of 1297 patients with liver cirrhosis admitted to our Clinic between 1980 and 1987 had hepatocellular carcinoma (HCC). This disorder was more frequent in patients with liver cirrhosis of dual etiology, alcoholic and post-hepatitic (9.9%), than in those with liver cirrhosis of unknown (7.82%), alcoholic (9.35%) or post-hepatitic (5.16%) etiology. The mean age of the patients with HCC of dual etiology (51.2 years) was significantly lower than that of the other three groups (61.0, 62.0 and 64.5 years, respectively; p less than 0.001). The conclusion is that in patients with liver cirrhosis of dual etiology the onset of HCC is frequent and precocious. This fact must be considered in epidemiological studies, in the prognosis and in the clinical management of the patient since early diagnosis is of importance in deciding therapy.

Hepatic encephalopathy may complicate chronic liver diseases and portosystemic shunting. Recently it has been suggested that a change in the blood amino acid pattern (with elevated phenylalanine, tyrosine, methionine and depressed branched chain amino acids) and increased levels of octopamine and phenylethanolamine (a false neurotransmitter) are related causally to neurological symptoms. Previous works have suggested that an amino acid mixture of special formulation (enriched in branched chain amino acids and poor in aromatic amino acids) can normalize the plasma amino acid levels and consequently improve the neurological state. In order to test the actual therapeutic effect of these specially formulated solutions, the following therapeutic protocols were administered to 3 groups of cirrhotic patients: group 1 (15 cases): lactulose; group 2 (8 cases): special amino acid solutions; group 3 (8 cases): special amino acid solutions and lactulose. Clinical, laboratory and EEG examinations in a preliminary experiment, before and after treatment, showed that the best effect was obtained by the combined treatment with amino acid solutions and lactulose.