M. Delle Monache

Liver Pathology in Cytomegalovirus Infection Associated with Hepatitis B Virus

A retrospective study was carried out in 56 patients to establish the association of cytomegalovirus (CMV) with active or inactive hepatitis B virus (HBV) infection as a possible risk factor in the development of severe liver disease. Patients with positive CMV serology and active or inactive HBV infection had elevated alanine aminotransferase activity and had a relatively high incidence of more severe lesions (chronic hepatitis and active cirrhosis), In the absence of CMV, only one case of cirrhosis was identified compared with seven cases of hepatic fibrosis. By analogy with hepatitis C virus, CMV may bring about activation of the host inflammatory response against hepatocytes following HBV infection, resulting in the development of severe hepatitic disease.

Faecal elimination of steroids in rats after oral administration of mepartricin.

Treatment of both male and female rats with 5 IU/day mepartricin for 7–10 days administered by gastric tubing resulted in an increased faecal excretion of some steroids. Mean rate of elimination of total oestrogens was enhanced by 45% in male rats and by 14% in female rats, and the average excretion of conjugated oestrogen was also increased in the female animals. Faecal elimination of cholesterol was 37% and 42% higher in male and female rats, respectively, after mepartricin treatment, and in male rats plasma concentrations of cholesterol were reduced following treatment. It is suggested mepartricin acts either by changing the intestinal flora or by acting directly on the steroid moieties, and it is speculated that a similar mechanism may occur in man.

Elevated alanine aminotransferase in blood donors : Role of different factors and multiple viral infections

Many different aetiological agents stimulate alanine aminotransferase (ALT) production. Viral markers and other aetiologies were investigated in 2166 individuals, randomly selected from 10 000 consecutive blood donors. Elevation of ALT was found in 10.8% of subjects. Grouping donors according to ALT level and correlating with, respectively, hepatitis B core antibody (HBcAb), cytomegalovirus antibody alone, or associated with HBcAb, showed similar findings (high ALT 11.1%, normal 11.6%; high 85.4%, normal 81.4%; high 10.2%, normal 11.0%, respectively). Hepatitis C virus (HCV) antibody was found to be significantly associated with elevated ALT levels (high 1.7%, normal 0.26%). Other causes of ALT elevation were alcohol abuse (17%), obesity (25%) and dyslipidaemia (38%), but in 11% there was no obvious aetiology. Although HCV is a rare cause of elevated ALT in blood donors, it seems to be the only virus, among those tested, to account for liver damage. This may be due to the non-protective role of HCV antibody, the low specificity of ALT, or the pathogenic role of uninvestigated viruses.

What Kind of Hepatitis

Finding one major hepatotropic virus may not be enough to identify the aetiology of liver disease when risk factors are present, particularly in patients with past or present infection with other viral agents, or chronic liver disease. The pathogenic process in these cases is often complex. In the five cases we report, acute hepatitis (initiated by halothane, cytomegalovirus or Epstein-Barr virus) preceded the reactivation of hepatitis B infection, and these events occurred in patients with chronic hepatitis C infection. Each case demonstrates how several viruses can be implicated in the development of hepatitis, either as single agents or via cross-activation of T cells. The nosography of hepatitis, therefore, and the optimum therapeutic choices, can puzzle the clinical team.

Changes in the Plasma Pattern of Sex Steroids in Patients with Liver Cirrhosis Treated with Mepartricin

Mepartricin was given to cirrhotic patients in order to evaluate its effect on the imbalance of sex steroids which is typical of this disorder. Patients were divided into two groups: one group received placebo (n=19) and the other received 150000 IU/day mepartricin for 30 days (n=19). The patients were evaluated by separate medical staff who were unaware of the treatment. Mepartricin significantly decreased the plasma concentration of testosterone, oestradiol and prolactin as compared with the values at the start of the trial, while no significant changes were seen in the occurrence of gynaecomastia. No relevant changes were seen in patients receiving the control, except for a slight increase in the peripheral concentration of androstenedione, aldosterone and follicle stimulating hormone.

Lymphocyte Function Tests in Cirrhotic Patients Under Treatment with Spironolactone and Potassium Canrenoate

This controlled study in cirrhotic patients investigated whether two antialdosteronic steroids, spironolactone (100–200 mg/day; n=12 patient pairs) and potassium canrenoate (50–100 mg/day, n=32 patient pairs) which are reported to bind to intracellular membranes and modify cytochrome P-450, could also produce nuclear changes. The model used was the response of peripheral lymphocytes to blastogenic agents by studying lymphocyte sub-populations. No changes occurred in the B- and T-lymphocyte sub-populations or in the helper and suppressor sub-types. The response to the blastogenic agents, phytohaemagglutinin and purified protein derived from mycobacteria, did not change significantly from before entry into the study to the follow-up (18.1 ± 2.9 months). All control patients (n=44 patient pairs) had slightly greater mitogenic activity compared with patients treated with spironolactone; no difference was found when control patients were compared with patients given potassium canrenoate. The difference between spironolactone and potassium canrenoate might be due to toxicity caused by the thio group of spironolactone. Overall, however, both drugs may be regarded as safe, in terms of effects on lymphatic tissue, occurring during the course of cirrhosis.

597 SERUM/ERITROCYTE RIBAVIRIN X 100 RATIO AS AN INDICATOR OF SVR IN HCV GENOTYPE-1 PATIENTS OBTAINING EVR

ackground. Virologic predictors during treatment with eg-interferon and ribavirin of hepatitis C are useful as hey allow early discontinuation of an unnecessary and xpensive treatment in non-responders. In this setting early irologic response (EVR), defined as viral load decline 2 log10 or undetectable HCV-RNA at week 12 of treatents has emerged as a useful tool to continue treatment. nfortunately, while EVR negative predictive value (NPV) s high, as approximately 2% only of patients not matchng EVR may achieve a sustained virological response SVR), the positive predictive value (PPV), in particular in enotype-1 patients, is low (∼60%). Other indicators may be eeded to predict SVR and in particular in those obtaining VR. im. To evaluate the usefulness of serum and eritrocyte ribvirin levels in predicting SVR in HCV genotype-1 patients ndergoing peginterferon + ribavirin treatment. ethods. 30 HCV genotype-1 patients (22 M/8F mean age 5.2± 13.6 years) undergoing a standard treatment schedle (Peg-IFN 180 mcg weekly + ribavirin 1000 or 1200 mg aily, according to body weight) were included in the study. lasma and eritrocyte ribavirin levels were evaluated in all atients at week 12 and at week 24 in those obtaining EVR nly. Ribavirin concentration was evaluated by high perforance liquid chromatography after solid phase extraction and mploying 3-methyl-cytidine as internal standard. Patients iochemical data were also recorded. esults. There was no difference among EVR and nonVR patients in terms of serum and eritrocyte ribavirin oncentration at week 12. At week 24, EVR patients obtainng SVR exhibited higher levels of ribavirin in serum nd lower in eritrocytes, in comparison with non-SVR atients (serum 14.1± 10.5 M vs. 5.9± 4.1 M; p< 0.02; ritrocyte 1072± 420 M vs. 1793± 903 M; p< 0.02). hen ([serum ribavirin]/[eritrocyte ribavirin]× 100) ratio as compared among these two groups, the difference was nhanced (1.6± 1.5 vs. 0.4± 0.34; p< 0.01). Receiver operting characteristic (ROC) curve analysis identified a cut-off or ([serum ribavirin]/[eritrocyte ribavirin]× 100) ratio in redicting SVR of 0.6, with a NPV of 80% and a PPV f 85%, while those related to EVR were 100% and 63%, espectively. onclusion. ([serum ribavirin]/[eritrocyte ribavirin]× 100) atio at week 24 seems to be an 85% indicator of SVR in a I p n isease 41 (2009) A1–A45 A35