Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.

The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies. Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL.

[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.

Serum Levels of Soluble IL-2R, CD4 and CD8 in Chronic Active HCV Positive Hepatitis.

The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation ofthe immune system, in patients with histologically verified chronic active hepatitis associated to hepatitis C virus infection, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD8 were found in patients with chronic active hepatitis compared with controls. In contrast no difference was found for soluble CD4 values in the two groups. No correlations were found for both sIL-2R and sCD8 and these two molecules with other parameters of liver function. These results indicate that in these patients there is a general activation of the immune system, but the lack of correlation with parameters of liver function strengthens the suggestion that this activation does not play a role in the pathogenesis of chronic type C hepatitis.

[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.

[Maternal-fetal transmission of infection with hepatitis B virus: evaluation of viral markers in maternal and fetal biological materials and relation with the vaccine response]. / Trasmissione materno-fetale dell'infezione da virus dell'epatite B (HBV): valutazione dei marcatori virali in materiali biologici materni e fetali e relazione con la risposta vaccinale.

From July 1984 to September 1987, 981 women at third trimester of pregnancy were screened for HBsAg. 26 women were identified as being HBsAg carrier. The study of HBV markers and anti-HBV antibodies was conducted on these women and their offspring to evaluate the presence of intrauterine infection, and the newborns response to passive active immunization in relationship to their markers status during pregnancy. HBsAg, HBeAg, anti-HBe and anti-HBc were assayed on the plasma drawn form the mother, on the amniotic fluid drawn by transabdominal amniocentesis and on funicolar blood samples drawn immediately after delivery. IgM anti-HBc were assayed on amniotic and funicolar samples. HBsAg, anti-Hbc and anti-Hbe were present in 42.8%, 100% and 50% of amniotic samples; whereas the percentage of the same markers in funicolar samples were 50% for HBsAg and 100% for anti-HBc and anti-HBe. In no amniotic or funicolar samples were IgM anti-HBc antibodies present. Anti-HBs, anti-HBc and anti-HBe were assayed on the newborns at 2, 16, 12, 18 months to evaluate the response to immunization. Response to passive-active immunization was protective in all newborns independently from their antigenic status during intrauterine life. Anti-HBc antibodies were cleared within 18 months from delivery, while anti-HBs got a protective title within 6 months from delivery, persisting in 88.8% of cases at 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

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.

Peripheral nerve involvement in chronic liver disease. Clinical and electrophysiological study.

A clinical and electrophysiological study was carried out on 19 selected patients with chronic liver disease. Clinical signs of peripheral nerve involvement were found in 4 patients (21%); while electrophysiological impairment was present in 11 patients (57.8%). These abnormalities were mostly limited to the sensory and motor fibers of the tibialis posterior nerve. Our data confirm the presence of peripheral nerve involvement in chronic liver disease, and that it may be evidenced by careful electrophysiological examination.

[Clofibrate hepatitis. A case report]. / Epatite da clofibrato. Descrizione di un caso.

The case of a patient who developed hepatitis during treatment with clofibrate is reported. The first attack of hepatitis, which resolved after the drug was suspended, was followed by another at rechallenge with a similar drug, fenofibrate.

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.

[Etiopathogenetic considerations on a case record of cirrhotic patients from western Sicily]. / Considerazioni etiopatogenetiche su una casistica di pazienti cirrotici della Sicilia occidentale.

In 38.6% of 88 patients without anamnesis of alcoholism and/or chronic exposure to hepatotoxic drugs, selected among 120 cirrhotic subjects subsequently observed, the illness was HBV related. Markers indicating active viral replication (anti-HBc, HBsAg, HBeAg or anti-HBe) were detected in 48% of patients with active cirrhosis, and in 26% with inactive cirrhosis. It is suggested that high titers of CF antibodies anti-HSV and anti-CMV observed in several patients, indicate either reactivation of latent infections or over-infections. The absence of alcoholism and/or chronic exposure to hepatotoxic drugs, and the absence of viral markers, suggest in 61% of the 88 cirrhotic subjects either a nonA-nonB viruses etiology of the illness, or other etiological factors that escape available diagnostic and prophylactic procedures.

[Serum monoamine oxidase (MAO) as a prognostic indicator in chronic active hepatitis. II]. / La monoaminossidasi sierica (MAO) come indice prognostico della epatite cronica attiva. Nota II.

Aim of this study was to evaluate the prognostic value of sMAO activity, assayed by benzylamine colorimetric method. Has been studied the correlation between clinical signs of portal hypertension (splenomegaly, ascites and varices) and sMAO levels; there was a significant increase of enzyme activity in chronic active hepatitis (CAH) with splenomegaly vs. CAH without, and in liver cirrhosis (LC) with splenomegaly and/or varices vs. LC without; there was also a correlation between sMAO and gamma-globulins levels in CAH and not in LC patients. In conclusion has been discussed the prognostic value of sMAO activity in CAH.

[Serum monoamine oxidase (MAO) in the differential diagnosis of chronic liver disease. I]. / La monoaminossidasi sierica (MAO) nella diagnostica differenziale delle epatopatie croniche. Nota I.

Aim of this study was to evaluate the diagnostic value of serum MAO activity (sMAO) in chronic liver disease. sMAO has been assayed by benzylamine colorimetric method. No statistically significant differences of sMAO values have been found between controls and acute viral hepatitis or various diseases patients. Differences instead between controls and patients sMAO values (chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis) were statistically significant (p less than 0.005).