Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

Use of alcohol and drugs in the view of people living with HIV/AIDS: a qualitative study.

OBJECTIVE: To investigate the meaning of the experiences of patients infected by HIV using antiretroviral therapy, regarding the use of alcohol and drugs. STUDY DESIGN: A qualitative phenomenological study. METHOD: A total of 25 patients receiving antiretroviral treatment participated in the investigation, of which 14 were male and 11 were females, who expressed their feelings and perceptions through participation in focus groups and the interpretation of costumes. The empirical material was transcribed in full and later organized and analyzed using the phenomenological method. RESULTS: Based on this amusing experience we realized that participants were unaware of the effects of the use of alcohol and drugs in the AIDS progression. Since they have kept with their smoking and alcoholism habits to be accepted in a social group and consequently prevent prejudice. We believe that our health education strategy was adequate to improve antiretroviral therapy, since it helped in subject comprehension and patients self-care body expression. CONCLUSION: This phenomenological study made it possible to understand the experience of patients living with HIV regarding the use of alcohol and drugs, and contributes to the planning and implementation of intervention programs based on a participative model of care, with a view to prioritizing the holistic aspects involved in the treatment of people living with HIV/AIDS.

Successful treatment of hepatitis C virus infection with sofosbuvir and simeprevir in the early phase of an allogeneic stem cell transplant.

Currently, a lack of consensus exists on how to manage a hepatitis C virus (HCV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ribavirin alone, or in combination with interferon, has been the mainstream therapy for HCV infection after transplantation. However, very few patients have been regularly treated owing to concerns about poor tolerability, frequent side effects, and limited efficacy. The present case illustrates the striking efficacy of the combination therapy of sofosbuvir with simeprevir, early after transplantation, as it was able to completely eliminate viral replication within 1 month of initiation of treatment. Moreover, tolerance was good, with only minor interactions between the immunosuppressive drugs. This case report supports the feasibility of using this combination therapy early after allo-HSCT for patients with HCV infection.

Preliminary X-ray crystallographic study of adenylosuccinate synthetase from Escherichia coli.

Adenylosuccinate synthetase, a dimeric enzyme of 96,000 Mr, catalyzes the first committed step toward the de novo biosynthesis of AMP. Large, single crystals of adenylosuccinate synthetase from Escherichia coli grow from solutions of polyethylene glycol and ammonium sulfate. Crystals from ammonium sulfate belong to the orthorhombic space group P212121 with unit cell parameters a = 79.0 A, b = 70.2 A and c = 152.6 A. Crystals from polyethylene glycol belong to the space group P21, having unit cell parameters of a = 71.16 A, b = 71.99 A, c = 82.95 A, and beta = 71.52 degrees. The asymmetric units of both crystal forms probably contain the entire dimeric enzyme.

Clinical evaluation of drug-induced hepatitis.

OBJECTIVE: To ascertain the epidemiological characteristics, clinical symptoms, and evolution of drug-induced hepatitis over the last 22 years. EXPERIMENTAL DESIGN AND SUBJECTS: An observational, retrospective study between 1982 and 1993, and prospective study between 1994 and 2003. All patients in our department diagnosed with having drug-induced hepatitis were studied analyzing epidemiological (age, sex, cases per year, hospitalization) and clinical features (previous liver disease, hepatic symptoms, laboratory results), and follow-up (complete recovery or chronicity). RESULTS: A total of 61 patients were diagnosed as having drug-induced hepatitis, 26 men and 35 women (57%), mean age 52.4 years +/- 17 years, of which 72.2% were older than 40 years. A total of 43% were admitted to hospital. In 87% of cases, two or more drugs were involved, the most frequent being antituberculosis (19 cases), psychotropic (26 cases), and non-steroidal anti-inflammatory drugs (45 cases). Evolution showed that 94% of patients recovered after the withdrawal of suspected causal drugs. CONCLUSIONS: The incidence of drug-induced hepatitis is higher in patients over 40 years of age, it being more common in females. Non-steroidal anti-inflammatory, psychotropic, and anti-tuberculosis agents were the main drugs involved. Most patients made a complete recovery after withdrawal of the suspected causal drug.

Interferon decreases serum lipid peroxidation products of hepatitis C patients.

Thiobarbituric acid reactive substances (TBARS) concentration in serum has been determined in healthy subjects and in patients suffering acute hepatitis and chronic cases of hepatitis C. Treatment with interferon of the chronic active hepatitis C patients, 5 x 10(6) U three times a week during 2 months, led in those patients whose SGPT activity normalized in serum, to a concomitant decrease in serum TBARS content. The possible theoretical involvement of peroxidation and antioxidants in this beneficial effect of interferon in hepatitis C patients is discussed. The results presented confirm the value of TBARS as laboratory test in the management of liver diseases and as a useful tool for the study of pathogenic and/or therapeutic mechanisms of this viral infection.

Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients.

Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than before it (p < .002). Associating the histopathological findings in each of the 48 biopsies performed, with serum malondialdehyde and alanine aminotransferase activity levels, of the sample obtained the same day of biopsy, a much better correspondence with the histopathological severity was observed for malondialdehyde concentration than for alanine aminotransferase activity. These levels decreased significantly after interferon treatment. However, when the patients were grouped in responding (group I; n = 9) and non-responding (group II; n = 15) to interferon treatment, according to the histopathological findings before and after interferon, the values of group I before interferon treatment were significantly higher than group II (p < .03). Thus, a potential predictive value could be ascribed to the serum malondialdehyde levels before interferon treatment in these patients. We propose the utility of the specific assay of malondialdehyde for the clinical management of chronic hepatitis C patients.

Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis.

PURPOSE: To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS: 967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study. Monitoring for hepatocellular carcinoma was scheduled at 3- to 6-month intervals. The mean (+/-SD) length of follow-up was 60.3+/-51.7 months (range 6 258). RESULTS: During the observation period, hepatocellular carcinoma developed in 64 patients. The calculated annual incidence was 2.1%. The probability of being free of liver cancer was 92% at 5 years, 80% at 10 years, and 69% at 15 years. Age was the only independent risk factor for the development of malignancy in the multivariate analysis. There were no differences according to male sex, alcohol abuse, and chronic hepatitis B and C virus infection. CONCLUSIONS: The annual incidence of hepatocellular carcinoma was 2.1%. These results, although confirming that age is a risk factor for hepatocellular carcinoma in cirrhosis, indicate that alcohol abuse, male sex, and concurrent hepatitis B and C virus infection do not involve a higher risk of developing liver cancer.

Nickel-induced proteins in human HaCaT keratinocytes: annexin II and phosphoglycerate kinase.

It has been established in previous in vitro experiments with human HaCaT keratinocytes that nickel becomes cytotoxic at concentrations higher than 100 microM and that it is accumulated mainly in the cytosolic fraction (Ermolli et al., 2000). The aim of this work was to search possible biomarkers of metal insult, i.e. nickel-binding proteins or proteins differentially expressed in the cytosolic fraction of nickel-exposed cells (up to 1 mM nickel) as compared to controls. Cytosolic proteins were studied by isoelectric focusing (IEF) and two-dimensional gel electrophoresis (2-DE). Separation by IEF revealed nickel-induced changes in the abundance of cytosolic proteins as visualised with nickel-nitrilo-triacetic-alkaline phosphatase (Ni-NTA-AP) in blots. The cytosolic fraction of cells incubated with nickel, at concentrations over 100 microM, showed nickel binding components which were absent or present in significantly lower amounts in control cells. These proteins had isoelectric points (pIs) 6.9, 7.7 and 8.5. After 2-DE silver- and protein staining significantly increased abundance of four proteins was observed. Their pI values corresponded to those of the nickel binding ones seen after IEF. A protein with pI 6.9 had a molecular weight estimated to 38 kDa, two proteins with pI around 7.7 showed molecular weights of 57 and 22 kDa, respectively and another protein with pI of 8.5 had a molecular weight of 33 kDa. The increased abundance of these components, both in IEF experiments and in 2-DE, correlated with the nickel concentration in the culture media. N-terminal amino acid sequencing and database search allowed identification of one a protein as phosphoglycerate kinase and another one as annexin II. The involvement of these proteins in cellular functions and their possible implications in the mechanism of nickel toxicity in keratinocytes are discussed. Some of these proteins may be biomarker candidates for effects of nickel exposure in human keratinocytes.

Nickel, cobalt and chromium-induced cytotoxicity and intracellular accumulation in human hacat keratinocytes.

Nickel, cobalt and chromium can induce allergic contact dermatitis (ACD) and may provoke irritant reactions in the skin. This study aimed at investigating cytotoxicity and cell viability along with intracellular metal accumulation in HaCaT human keratinocytes exposed to soluble forms of nickel, cobalt or chromium. The EC50 (24 h) values as detected by MTT test were 30 microM for sodium chromate (Na2CrO4), 475 microM for cobalt chloride (CoCl2) and 600 microM for nickel chloride (NiCl2). Chromium chloride (CrCl3) was not toxic up to 1 mM. No clear effects were observed after 4 h, but 24-h treatments with 1 mM CoCl2 or 10 microM Na2CrO(4) were found to almost completely abolish the ability of the cells to form colonies, whilst 1 mM NiCl2 reduced cellular survival to only 70% of control cultures. Intracellular accumulation of metals was evaluated by the use of radioisotopes at the EC50 value and at 1/10-1/5 of this concentration. Accumulation of Na2(51)CrO4 was linear with increasing dose. This was not the case for 63NiCl2 and 58CoCl2. All the metals were accumulated preferentially in the cytosols; 96% or more for 63NiCl2, approximately 90% for 58CoCl2 and 60-70% for Na2(51)CrO4. Finally, it was observed that HaCaT human keratinocytes can concentrate the metals present in the media up to 3.9 and 12.5 times for NiCl2 and CoCl2, respectively, and up to 167 for Na2CrO4. These striking metal intracellular accumulation patterns, which have not been earlier described in keratinocytes, highlight the relevance of searching for specific biomarkers of early cellular toxic effects, such as cytosolic proteins that bind the metals.

Vanadium effect on the activity of horseradish peroxidase, catalase, glutathione peroxidase, and superoxide dismutase in vitro.

The effect of vanadium (V) on the activity of horseradish peroxidase, catalase, glutathione peroxidase, and superoxide dismutase has been studied. A competitive inhibition pattern was evident for vanadate ions on the activity of horseradish peroxidase (Ki = 41.2 microM). No significant inhibitory effects were found when V(V) was tested with catalase and when either V(IV) or V(V) were assayed with glutathione peroxidase. For the latter, the effect of V on the different components of the reaction system was investigated. V(V) did not significantly affect SOD activity when assayed with the sulfite method, which is devoid of interferences with V(V); however, there was an apparent inhibitory dose-response pattern for either V(IV) or V(V) using the pyrogallol assay, owing to an interference of pyrogallol with the metal. Besides, no significant binding of V(IV) or V(V) to the enzyme could be demonstrated. The lack of a direct inhibitory effect of V on the activity of the main antioxidant enzymes suggests that many biological and toxicological effects of V may be mediated more by oxidative reactions of the metal or of its complexes with physiologically relevant biomolecules than by a direct modulation of enzymatic activities.

Effect of L-carnitine upon ammonia tolerance test in cirrhotic patients.

In a group of liver cirrhosis (LC) patients subjected to a rectal ammonium overload test, the effect of L-carnitine on ammoniemia and on the type A numerical connection and star clock psychomotor tests has been evaluated. On comparing 40 LC patients given L-carnitine with 40 control cirrhotics given a placebo, no significant differences were observed in ammonium levels after performing the overload test in both groups. However, on studying the patients with the greatest liver involvement, those given L-carnitine showed smaller elevations in ammoniemia and better responses to the psychometric tests than those receiving the placebo. The results obtained emphasize the need to continue testing the effect of L-carnitine using either similar tests or carrying out long-term evaluations to determine its protective effect in the appearance of hepatic encephalopathy, perhaps even including its evaluation in the treatment of established encephalopathy.

Plasma sulfobromophthalein disappearance in Gilbert's syndrome.

BACKGROUND/AIMS: We studied the metabolism of sulfobromophthalein and its relationship with serum bilirubin levels in 40 patients with Gilbert's syndrome (type I 30; type II 6; type III 4). MATERIAL AND METHODS: Plasma sulfobromophthalein disappearance studies were carried out and 72 hours later, serum bilirubin concentrations (total and unconjugated fraction) were determined at baseline and after 24 and 48 hours of dietary restriction to 400 calories/day. RESULTS: The fractional transfer rate of sulfobromophthalein from plasma to liver was significantly higher in types I (14.7 +/- 3.4 ml/min) and II (14.9 +/- 2.7 ml/min) than in type III (8.7 +/- 1.5 ml/min). The fraction of the plasma sulfobromophthalein pool irreversibly cleared per min was significantly higher in type I (12.2 +/- 2.6 ml/min) than in types II (9.5 +/- 1.5 ml/min) and III (9.3 +/- 3.8). In all patients, serum bilirubin concentrations were significantly higher after fasting as compared with baseline. There was a significant correlation between the increments of serum unconjugated bilirubin levels after the fasting test and the transfer rate of sulfobromophthalein from plasma to liver (F = 9.8411, r = -0.4535, p = 0.003). CONCLUSION: These findings indicate the presence of an active uptake system shared by bilirubin and sulfobromophthalein.

Aluminum effect on the activity of superoxide dismutase and of other antioxygenic enzymes in vitro.

The effect of Al on superoxide dismutase (SOD) and on other antioxygenic enzymes: horseradish peroxidase, catalase, and glutathione peroxidase, has been investigated in vitro. In the case of SOD, the effect of metal chelators (EDTA and deferoxamine) and a possible synergistic effect with iron salts have also been tested using the pyrogallol assay. There is no significant inhibitory effect of Al on the activity of any of the above-mentioned enzymes. Noticeable increases in SOD activity were observed when metal chelators were added to the medium, but not when high concentrations of Al were present too, in the case of deferoxamine (DFO). The former fact seems to be a consequence of the chelation of transition metal ions that catalyze pyrogallol autoxidation by a mechanism not inhibitable by SOD, interfering in its action, which may account for part of the DFO antioxidant effect observed in vivo. The latter phenomenon could be owing to a saturation of the chelating capacity of DFO by an excess of Al present in the medium, which should bring the system back to the interfering conditions explained above. It can be concluded that Al, either in the presence or in the absence of iron salts, does not inhibit SOD activity in vitro. Moreover, no significant binding of Al to SOD was demonstrated, and the amounts of its metal constituents, Cu and Zn, were not affected by preincubation of the enzyme with Al. The effect of the different compounds tested on the rate of autoxidation of the indicating scavenger, pyrogallol, and a suitable hypothesis on their role in the oxidation process are also discussed.

Vanadate as an inhibitor of plant and mammalian peroxidases.

Vanadate ions are shown to inhibit horseradish, squash, and rat intestinal peroxidases by following the reaction spectrophotometrically in a wide range of vanadate concentrations. I50 in phosphate buffer were 43, 9.4, and 535 microM, respectively. No inhibitory effect was found on cow milk lactoperoxidase and beef liver catalase. Gel filtration of peroxidases in the presence of vanadate, as carried out by radioactive 48V for horseradish peroxidases (either in aerobic or anoxic conditions) and neutron activation analysis (NAA) for squash peroxidase, demonstrated a binding of vanadium to these enzymes in stoichiometric amounts. Electron paramagnetic resonance spectra of the eluted peaks for the former peroxidase indicated that vanadium is in the +5 oxidation state, but an equilibrium between V (V) and V (IV) in the assay conditions cannot be discarded. Although the inhibitory mechanism remains obscure, some hypotheses are considered. The potential implications that the inhibitory effect of vanadium might have on plant and animal metabolism are also discussed.

Effects of trace metal compounds on HIV-1 reverse transcriptase: an in vitro study.

The effect of 44 different metal ions (Ag+, Al3+, As(O-)2, Au3+, Ba2+, Be2+, Bi3+, Cd2+, Ce3+, CO2+, Cr(O2-)4, Cr3+, Cs+, Cu2+, Fe3+, Fe2+, Ga3+, Ge4+, Hg2+, Ir4+, La3+, Li+, Mn2+, MO6+, Ni2+, OS4+, Pb2+, Pt4+, Rb+, Rh3+, Sb5+, Se(O2-)4, Se(O2-)3, Sn2+, Sr2+, Th4+, T1+, U(O2+)2, V(O-)3, VO2+, W(O2-)4, Y3+, Zn2+, and Zr4+) on the activity of the reverse transcriptase (RT) of the human immunodeficiency virus (HIV-1) was investigated in vitro. For this study, the RT activity assay was carried out by means of an enzyme-linked immunosorbent assay (ELISA) kit, using the template/primer hybrid poly(A) oligo(dT)15, which required some modifications: (1) possible interfering metal chelators (such as EDTA) in the original lysis buffer were avoided, and a new buffer (50 mM Tris-NO3, pH 7.8) was used throughout; (2) an amount of 2 ng of RT per well was considered to be optimal after checking the linearity of the reaction with increasing amounts of enzyme; (3) an incubation temperature of 37 degrees C and an incubation time of 1 h were chosen after preliminary studies in a wide range of temperature and time. At an incubation temperature > or = 40 degrees C, there was a dramatic loss of enzymatic activity. In addition, when RT alone was preincubated for 1 h at 5 degrees C, 25 degrees C, and 37 degrees C, there was a large (83%) loss of activity at 37 C as compared to that at 5 degrees C. These results are indicative of enzyme thermolability, which is higher in the absence of substrates. The effect of metal ions on RT activity was tested using two different metal salt concentrations (10(-4) M and 10(-5) M). Under such experimental conditions, the presence of five metal ions (Pt4+, Ag+, Rh3+, Zn2+, and Hg2+) decreased the RT activity in a dose-response fashion. The observed order of effectiveness with respect to inhibition was Pt4+ > Ag+ > Rh3+ > Zn2+ = Hg2+. Estimated mean inhibitory concentrations (IC50) were 7.8 microM for (NH4)2PtCl6, 14.1 microM for AgNO3, 46.8 microM for RhCl3, 53.7 microM for Zn(SO)4, and 56.2 microM for Hg(NO3)2. Because these data are of the same order of magnitude as the corresponding values related to other RT inhibitors used in anti-AIDS therapy, metal compounds or their derivatives could give an interesting contribution in the development of new RT inhibitors for clinical use.

[Epidemiologic observations on the subject of phlebopathy of the legs and its dermatologic complications]. / Osservazioni epidemiologiche in tema di flebopatie degli arti inferiori e loro complicanze dermatologiche.

The authors carried out an epidemiological study on a group of 10032 patients with chronic venous insufficiency, composed of 2686 males (26.77%) and 7346 females (73.23%). The case report is divided into varicose diseases (83.30%) and sequelae of deep vein thrombosis (16.70%). As well as the relationship between sex and age is considered rate of dermatological complications, with regard both to the type of venous diseases (65.54% varicose and 34.46% post-thrombotic) and to their clinical manifestations. As well as any family connection, various environmental factors are taken into account such as the patient's work, noxae iatrogenic, pregnancy and obesity.

[A meta-analysis of controlled studies of the treatment of chronic hepatitis due to the hepatitis B virus]. / Metaanálisis de los estudios controlados de tratamiento de la hepatitis crónica por el virus B de la hepatitis.

BACKGROUND: Since the results obtained in controlled studies of antiviral treatment of chronic hepatitis by the hepatitis B virus are frequently insignificant the authors have undertaken a combined study of the different controlled trials with the meta-analysis technique. METHODS: The results of 7 controlled trials of treatment with adenosin arabinoside (AAR) and 18 published studies on therapy of a control group with interferon were studied. Meta-analysis was performed by two methods: Mantel expressing the results in odds ratio (OR) and Cochram-Dersimonian-Laird which consider the results in differences of risk (RD). RESULTS: The meta-analysis of AAR treatment shows a mean difference of response of 11% with no homogeneity among the different studies published. This lack of homogeneity may be due to the different selection criteria of the patients which determine very variable degrees of response. The controlled studies with interferon showed a mean difference of response of 20% with homogeneity of effects. No differences were observed in the degrees of response according to whether recombinant lymphoblastoid interferon was used or if the dose was of 5 or 10 megaunits per day. Non were differences observed in degrees of response with respect to the time in which the loss of viral DNA was evaluated. CONCLUSIONS: Following analysis of the results it was concluded that interferon is clearly effective in the treatment of chronic hepatitis B and based on published studies adenosin arabinoside demonstrate less efficacy.

Maximal biliary transport of sulfobromophthalein in patients with a T-tube placed in the common bile duct.

In 19 adult patients with choledocholithiasis who were operated on, excretion of free and conjugated sulfobromophthalein (BSP) in the bile collected through a T-tube inserted in the common bile duct was determined. The transport maximum (Tm) for BSP was calculated by the constant-infusion technique after an intravenous infusion of the dye at a rate of 0.3 and 0.09 mg/kg/min for the first and second hour, respectively. Free and conjugated BSP were measured in blood samples obtained at 30, 40, and 50 min of each hourly-infusion period, and in bile collected during the first 30 min (sample A) and between 30-50 min (sample B) after starting the first BSP infusion, and during the first 30 min (sample C) and between 30-50 min (sample D) after starting the second infusion. No correlations between Tm of BSP and glutathione transferase activity and between Tm and bilirubin and alkaline phosphatase in serum were found. Although there was an overall correlation between Tm of BSP and biliary excretion of BSP after 30 min of starting the BSP infusion (samples B, C and D) (r = 0.4716; P = 0.41), Tm values were always lower than recoveries of free BSP in bile. It seems that Tm of BSP (measured with the Wheeler's method) overestimates the actual values of biliary excretion of free BSP, and that the percentage of conjugated BSP in serum is related to the degree of impairment of biliary transport of BSP.

Clinical and morphological study of hepatocellular carcinoma associated with liver cirrhosis.

We studied 104 patients diagnosed with hepatocellular carcinoma on the basis of pathological findings, in order to establish differences between patients with and without liver cirrhosis in addition to carcinoma. Among the former we also tried to identify differences between patients with previously diagnosed cirrhosis and those in whom cirrhosis was diagnosed at the same time as carcinoma. No significant differences were observed between patients in whom cirrhosis was diagnosed before or at the same time as carcinoma in relation to age, sex, etiologic factors or Child-Pugh grade. Differences were found with regard to motives for suspecting a tumor, frequency of splenomegaly, and platelet and leukocyte counts. No significant differences were found between patients with and without cirrhosis except in some laboratory findings (leukocytes, platelets, erythrocyte sedimentation rate and gammaglutamyl transpeptidase higher in the latter group, and alpha-fetoprotein higher in the former). There were no significant differences between cases of hepatocellular carcinoma that appeared as the first manifestation of liver cirrhosis and those that were diagnosed in patients with known cirrhosis. The clinical and biological differences between patients with and without cirrhosis can be explained by the associated chronic hepatic disease.