Reliability of the bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCV-related hypertransaminasaemia.

AIM: To evaluate the reliability of the bright liver (BL) echo pattern on ultrasound to detect histological steatosis in chronic cryptogenic hypertransaminasaemia (CCH) and hepatitis C virus (HCV)-related forms of hypertransaminasaemia. MATERIALS AND METHODS: One hundred and fifty patients, 54 with CCH and 96 with HCV hypertransaminasaemia (76 genotype 1/2 and 20 genotype 3), were enrolled. Histological steatosis was measured as the percentage of hepatocytes involved. The reliability of the BL sign was estimated using the sensitivity, specificity, positive and negative predictive values. RESULTS: Histological steatosis was present in 102/150 patients (68%) divided into 59/96 (62%) in the HCV group and 43/54 (79.6%) in the CCH group (chi(2)=4.4; p=0.035). In a multivariate analysis, the variable associated with the BL echo pattern was steatosis percentage (p=0.0018). Steatosis percentage was higher in CCH group than in the HCV genotype 1/2 and 3 groups (p=0.02). The sensitivity of the BL echo pattern was 88% in the CCH group [confidence interval (CI) 95% 74-95] versus 61% (CI 95% 44-73) in the HCV genotype 1/2 group. The CI indicates that ultrasound can provide evidence for steatosis in a statistically significant way in the CCH versus HCV genotype 1/2 patients. In the genotype 3 group, the sensitivity was high (90%), but the limited number of cases limited the statistical significance due to the high CI. CONCLUSION: In CCH the BL echo pattern has excellent reliability in diagnosing steatosis, better than in HCV hypertransaminasaemia because of the higher prevalence and extent of steatosis.

Interferon-alpha alone versus interferon-alpha plus ribavirin in patients with chronic hepatitis C not responding to previous interferon-alpha treatment.

OBJECTIVE: To study the effects of monotherapy with leucocyte interferon-alpha (IFNalpha) versus IFNalpha + ribavirin in patients with chronic hepatitis C who were nonresponders to previous courses of recombinant or lymphoblastoid IFNalpha. DESIGN AND SETTING: This was a nonblind randomised study of outpatients at 3 centres in Palermo, Sicily, Italy. PATIENTS AND PARTICIPANTS: We recruited 72 patients (48 males, 24 females), mean age 48.8 +/- 6.6 years (range 31 to 63 years), with biopsy-proven chronic hepatitis C, predominantly genotype 1b. INTERVENTIONS: 24 patients (group A) received IFNalpha 6MU 3 times weekly for 6 months, and 48 patients (group B) received IFNalpha 6MU 3 times weekly + ribavirin 1200 mg/day for 6 months. ALT levels and adverse effects were monitored monthly, and hepatitis C virus (HCV) RNA levels were measured at study entry, at the end of treatment and after a 6-month follow-up. RESULTS: At baseline all patients were HCV-RNA positive and had ALT levels greater than twice normal. Mean post-treatment serum HCV-RNA levels were below baseline in group A, but the virus was eradicated in only 1 patient; 6 patients had normalised serum ALT levels. In group B at end of treatment, 12 patients were negative for HCV-RNA and serum ALT levels were normal in 18. At follow-up, all group A patients had elevated ALT levels and positive HCV-RNA. In group B, 3 patients were still negative for HCV-RNA and 4 had normal ALT. In 4 patients in group B, therapy was suspended because of anaemia, depression and decrease in neutrophil count; a flu-like syndrome was recorded with no frequency difference between groups. CONCLUSIONS: These results suggest that patients with chronic hepatitis C unresponsive to IFNalpha monotherapy could benefit from combination therapy with IFNalpha + ribavirin.

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis.

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.

[Serum zinc concentration and antibody response to hepatitis B vaccine in hemodialysis patients]. / Concentrazione sierica dello zinco e risposta anticorpale al vaccino anti-epatite B negli emodializzati.

The serum zinc concentration seems unlikely to be an important factor influencing immune response to hepatitis B vaccination in hemodialysis patients, on the basis of the following results: the absence of statistically significant differences in serum zinc concentrations between patients with absence of post-vaccine seroconversion or non protective seroconversion and patients with excellent seroconversion (anti-HBs concentrations over 124.6 mUI/ml); the association of protective antibody responses in 50% of non responders after an additional dose of HBV vaccine, without preliminary corrections of zinc balance.

[Correlation between values of alpha-1-fetoprotein and clinical manifestations of cirrhosis in the evaluation of a carcinomatous course of the disease. Preliminary data on case material on elderly patients]. / Correlazione fra valori di alfa-1-fetoproteina e manifestazioni cliniche della cirrosi nella valutazione di una evoluzione carcinomatosa della malattia. Dati preliminari su una casistica di pazienti anziani.

Early diagnosis of PHC development in cirrhosis is sometimes difficult through common tests excluding invasive diagnostic procedures; liver biopsy as a routine periodical control during the course of the disease is not advisable and AFP monitoring as a diagnostic test is preferable. The present study shows the results of a screening for AFP levels in a series of 113 cirrhotic patients aged over 50. 11.5% of them presented increased levels of serum AFP, indicating development of PHC. AFP elevated values resulted in 76.5% of cases associated with a previous HBV infection, and the risk of PHC development resulted sixfold greater in anti-HBc positive male cirrhotic patients. In patients with elevated AFP levels the prevalence of complications of cirrhosis resulted up to tenfold greater than in AFP negative patients.

[Incidence of anti-HCV positivity in a Sicilian population with liver diseases]. / Frequenza di positività per anti-HCV in una popolazione di epatopatici siciliani.

The discovery of virus C as an etiological agent of chronic liver disease (CLD) has modified previously-held concepts concerning the etiology of this disease. In a study of 581 consecutive patients with CLD, we confirmed that virus C was the sole agent responsible for it in 64.2% of all cases. Moreover, virus C was characteristically associated with virus B, alcohol consumption, and autoimmunity. When the various CLD were separated into subgroups, i.e., chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), and liver cirrhosis (LC), virus C continued to be the main etiological agent, varying from 60.5% to 68.3%: this suggested constant evolution from milder to more severe forms of liver disease. Virus B alone was found less frequently, probably thanks to the virtual elimination of post-transfusion hepatitis B and the anti-B virus vaccination which is now widely administered. Frequency was 15.2% in the CPH group but lower in the LC and CAH groups (7.4% and 6.3% respectively), suggesting that evolution from the milder to the more severe forms of liver disease may not occur. Finally, we confirmed a statistically significant difference in mean age between hepatitis C virus positive men and women (p < 0.0001): in men, frequency was higher in the 20- to 50-year-old group; in women it was higher in the 50+year-old group.

Acetylcysteine therapy for chronic hepatitis C: are its effects synergistic with interferon alpha? A pilot study.

OBJECTIVE: This trial reports the 6-month results of a pilot study using lymphoblastoid interferon alpha (IFNalpha) and acetylcysteine (N-acetylcysteine) separately and in combination in patients with chronic hepatitis C, genotype 1b, who were nonresponders to previous treatment with recombinant IFNalpha alone. PATIENTS AND METHODS: 21 patients were randomly divided into three groups of seven each. Group A was treated with lymphoblastoid IFNalpha 6MU three times a week for 6 months; group B received the same schedule of lymphoblastoid IFNalpha as group A plus acetylcysteine 1200 mg/day per os in two administrations, and group C received only acetylcysteine 1200 mg/day per os in two administrations. RESULTS: Mean serum alanine aminotransferase (ALT) levels at 6 months in groups A and B, but not in group C, were significantly lower than baseline values (p < 0.05 and p < 0.03, respectively). Two patients in group A (28.6%) and three in group B (42.9%), but none in group C, had normalised ALT levels at 6 months. During follow-up, levels flared in one group A and in one group B patient. Thus, at the end of follow-up one group A and two group B patients were sustained responders. At the end of therapy and follow-up, hepatitis C virus (HCV)-RNA was negative in one patient in group A and two patients in group B. As no serious adverse effects were observed, therapy was never interrupted or suspended. CONCLUSION: Acetylcysteine alone had no effect on hepatic cytolysis and viral replication; lymphoblastoid IFNalpha showed a modest, but better, response than recombinant IFNalpha, and the combination therapy, although in a limited number of patients, appeared to be more efficient than lymphoblastoid IFNalpha alone.

[Procollagen III and laminin in chronic viral hepatopathies]. / Procollagène III et laminine dans les hépatopathies chroniques d'origine virale.

OBJECTIVES: We measured serum concentrations of the N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in patients with chronic viral liver disease in the various stages of the clinical course, to judge their value in assessing liver fibrogenesis, and also compared them with a number of liver function tests and histological scores of inflammation and fibrosis. METHODS: Twenty-nine patients with chronic persistent hepatitis, 39 with chronic active hepatitis and 42 with liver cirrhosis were studied. The control group was composed of 45 healthy blood donors. Serum PIIIP and Lamp-P1 were determined by radioimmunoassay; hepatic function was measured by routine assay; liver fibrosis and inflammation were graded on a 0-3 score scale. RESULTS: A significantly higher increase in serum levels of PIIIP and Lam-P1 was found in the liver cirrhosis group compared with the other groups (p < 0.05). Serum PIIIP correlated with transaminase levels in the chronic active hepatitis group and with gammaglobulin and total bilirubin in the liver cirrhosis group. A positive correlation was found only with gammaglobulin and total bilirubin in the cirrhosis group. A positive correlation was found between serum PIIIP levels and the rating scale of liver necrosis. In contrast, for Lam-P1 values, a correlation with the rating scale of necrosis and fibrosis was found. CONCLUSION: Our findings confirmed the increase of PIIIP and Lamp-P1 in chronic viral liver disease, but because of the frequent overlap values, they cannot be used as substitutes for liver biopsy for diagnosis. The correlations with the histological findings indicate that these two markers can be used during the follow-up of patients receiving anti-inflammatory or anti-fibrotic treatment.

[Factors predicting the response to alpha-interferon therapy in patients with chronic hepatitis C]. / Fattori predittivi di risposta al trattamento con alfa interferone in pazienti con epatopatia cronica anti-HCV positiva.

Objective of the study was to identify predictive factors of response to treatment with interferon in patients with anti-HCV positive chronic liver disease. 92 anti-HCV positive patients, 51 with chronic hepatitis and 41 with active cirrhosis, were treated for 12 months with recombinant alpha 2a interferon at a starting dose of 6 MU TIW/6 months, followed by 3 MU TIW/6 months. Patients were considered responders (RS) when they presented normal serum ALT values both at the end of treatment and after 6 months of follow-up; relapsers (RC) those with normal ALT values at the end of treatment but with increase during the 6 months of follow-up and non-responders (NR) patients who had no beneficial effect on ALT levels during treatment. 21 patients were RS, 11 RC and 60 cases NR. Univariate analysis of pre-treatment factors showed that response to interferon was associated with absence of cirrhosis and lower gamma-GT levels in RS than in RC. Multiple logistic regression of these variables showed that gamma-GT levels and absence of cirrhosis were the only independent factors associated with response to treatment. In conclusion, in our series of patients, only two factors were confirmed useful in predicting response to interferon treatment and it is concluded that they must always be evaluated before starting treatment with interferon which is not without side effects and may not have beneficial effect.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

BACKGROUND/AIM: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center. PATIENTS: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al. RESULTS: Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR. CONCLUSIONS: This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.

[Counterimmunoelectrophoresis on cellulose acetate membrane with a commercial lyophilized antigen in diagnosis of human hydatidosis]. / Controimmunoelettroforesi (CIEP) su membrana di acetato di cellulosa, con un antigene liofilizzato del commercio, nella diagnostica della idatidosi umana.

A very simplified method of crossed over electrophoresis (CIEP) was employed with a lyophilized commercially produced antigen (previously submitted to several freezing and thawing) and cellulose acetate membrane, for the diagnosis of human hydatidosis. Results are as follows: active hydatidosis (surgically confirmed): number of sera tested 35; positive 32 (91%). Sera of patients with parasitic and non parasitic illnesses (especially malignancies of liver and lung) did not show any precipitin lines. The pattern of immunoprecipitation is characteristically in the form of an "upper lip" or a thick and undulating "streak". The very thin arcs of precipitation which are occurring in some control sera, are to be considered negative. These results indicate that with regard to the rule of the "three S" (specificity, sensitivity and simplicity) the method appears sufficiently satisfactory.

Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy.

This study was designed to assess patients with chronic hepatitis C (CHC) for the presence of thyroid autoimmunity and dysfunction, to evaluate the risk of thyroid disorders associated with interferon (IFN) therapy, and to survey the outcome of possible treatment-related thyroid injury. Out of 104 consecutive untreated patients (30 women and 74 men; mean age, 52.7 years), 8 (7.7%) were found seropositive for thyroid autoantibodies (ThyAb), whereas seropositivity in healthy controls was 1/98 (1.3%). The relative increase in risk of developing thyroid autoimmunity associated with CHC was 760% (95% CI, 220-1300%). No patients had abnormalities of thyroid function tests, but on IFN treatment, 3/3 patients showed a rapid over-range rise in circulating thyrotropin, which returned to normal after therapy discontinuation. In the other 5 seropositive patients who refused treatment, thyroid function remained normal. Out of the 58 initially seronegative patients who consented to IFN treatment, 9 (15.5%) developed thyroid autoimmunity. Seven of them (77.7%) had thyroid dysfunction: hypothyroidism in 4 cases, transient thyrotoxicosis in 2 cases. The last patient developed TSH-receptor antibodies and Graves' disease, requiring methimazole therapy. Thyroid function recovered in the former 6 cases following IFN discontinuation. In the 28 initially seronegative patients who refused IFN and participated in a preliminary tauroursodeoxycholic acid trial, antithyroglobulin antibodies alone appeared in one case, but no thyroid dysfunction was observed. The relative risk of thyroid autoimmune disorder associated with IFN therapy was 342% (28-636%). The patients with CHC were unlikely to develop thyroid dysfunction in the absence of IFN therapy, in spite of being ThyAb seropositive. Moreover, a considerable proportion of seronegative patients, when IFN-treated, developed thyroid autoimmunity and then thyroid dysfunction. Both in seropositive and seronegative patients immediate IFN discontinuation normalized thyroid function and hormone replacement therapy was not necessary.

Platelet thromboxane production in liver cirrhosis.

To determine whether platelet prostaglandin production in patients with liver cirrhosis was as impaired as platelet aggregation, serum thromboxane production was studied in 52 patients with liver cirrhosis; 12 patients had consumed more than 80 gr of alcohol/day, for more than ten years; 13 patients had also had diabetes mellitus for more than two years. A reduced thromboxane synthesis by platelets of liver disease patients was observed; the parallel decrease of both platelet thromboxane and serum PGE2 formation may also suggest a decrease in arachidonic acid availability for prostaglandin and thromboxane production. A smaller reduction of thromboxane and PGE2 formation in cirrhotics with diabetes mellitus or chronic alcohol intake was also observed.

HBV infection risk in hospital workers.

Prevalence of HBV infection markers and its association with some risk factors has been studied on hospital staff of the University Polyclinic of Palermo. The results show that male sex, job category (technicians, nurses, cleaners) and age are significantly associated with a higher prevalence of HBV infection markers; length of service and working in departments with a presumably higher exposure to blood did not result as a risk factor of higher prevalence of HBV infection when submitted to multiple regression logistic analysis. It is suggested that results of this study may be affected by the elevated spread of HBV infection in this area, and extra risk associated to hospital exposure is too small to be demonstrated.

[Hepatitis B virus infection in habitual sexual partners]. / Infezione da virus della epatite B in partners sessuali abituali.

Habitual heterosexual contacts of chronic HBV infection carriers show high prevalence of infection markers that does not result to be sex related, and results significantly associated to increase of age, presumably as a consequence of duration of exposure. Concomitance of habitual sexual contacts does not represent in an infected family setting a risk factor of higher prevalence of HBV infection, in respect of multitude of occurrences of unperceivable expositions to contagion.

Prevalence of hepatitis B virus infection in chronic users of hepatotoxic drugs and alcoholic cirrhotic patients.

Anti-HBc prevalence in alcoholics, chronic hepatotoxic drugs users, exposed to both these factors, and not exposed to alcohol and drugs cirrhotic patients was compared. Anti-HBc prevalence was significantly higher both in alcoholics and in hepatotoxic drugs users cirrhotic patients, and no statistically significant difference was found between the prevalence of anti-HBc in these two groups. In male cirrhotic patients the risk of HBV infection was 4.4 times higher in chronic hepatotoxic drugs users, 4.7 times higher in alcoholics, and 6.9 times higher in patients exposed both to alcohol and drugs. These results support the hypothesis that also chronic consumption of hepatotoxic drugs may be associated with a greater prevalence of HBV infection.