Barbara Mauceri

Controlled clinical trial to assess the response of recent heroin abusers with Chronic hepatitis C virus infection to treatment with interferon alpha-n2b

BACKGROUND Chronic infection with hepatitis C virus (HCV) is the most common infectious disease among heroin abusers, but it is recommended that specific treatment with interferon be delayed until at least 6 to 12 months after the end of drug addiction. OBJECTIVE We investigated the response of heroin abusers to interferon treatment shortly after the end of detoxification treatment with methadone. METHODS We studied 2 homogeneous groups of white Italian patients with chronic HCV infection: former male heroin abusers and males without a history of drug addiction. Tumor necrosis factor, interleukin-1beta, interleukin-2, activated monocytes, anti-HCV antibodies, HCV RNA, and alanine aminotransferase levels were assessed. Standard treatment was initiated with 5 MU interferon alpha-n2b administered subcutaneously once daily for 8 weeks. Patients with negative HCV-RNA findings at the end of 8 weeks received further treatment with 5 MU TIW subcutaneously for an additional 48 weeks. RESULTS Thirty of 47 patients in group A (former heroin abusers) and 30 of 30 patients in group B (controls) completed the study. Heroin abusers presented a significantly enhanced response to treatment compared with the controls. After 8 weeks, HCV-RNA test results were negative in 27 of 30 patients in group A (90.0%) and in 25 of 30 in group B (83.3%) (P = NS). Onset of relapse occurred significantly later in heroin abusers (mean [SD], 53 [3] weeks) than in controls (26 [2] weeks) (P < 0.05). Cytokine levels and activated CD11 antigen-expressing monocytes were significantly (P < 0.001) higher in heroin abusers than controls. CONCLUSION Heroin abusers with chronic HCV infection were successfully treated with interferon alpha-n2b soon after the end of detoxification treatment.

Can ultrasonographic findings of perihepatic lymphadenopathy promote investigations to detect possible presence of virus C infection in non-symptomatic subjects?

PURPOSE: Only early detection of non-symptomatic patients is able to arrest the diffusion of the non-symptomatic HCV infection and lead to prompt treatment. Our aim was to attempt to correlate the presence of perihepatic lymph nodes and hepatitis C infection and to assess whether ultrasonography can have a role to promote specific investigations for pre-clinical diagnosis of virus C infection. METHOD: We performed a controlled study on a cohort of 7974 subjects from a town of 27000 inhabitants on the eastern coast of Sicily. Serologic hepatitis A, B and C markers, alanine aminotransferase levels and abdominal ultrasound examination according to size and number of peri-hepatic lymph nodes were performed on blind basis. RESULTS: One or more pathological lymph nodes were present in 684/7974 subjects. Haematochemical tests revealed the presence of anti-HCV positivity in 528/684 subjects with pathological lymph nodes and in 8/7290 subjects without pathological lymph nodes, there being a significant difference (P<0.0001) between the two groups. CONCLUSION: Our results confirm the association between perihepatic lymph nodes and virus C infection. Correct diagnostic assessment of this datum could lead not only to early diagnosis by specific blood test for HCV and consequent prompt aimed treatment, but could pave the way for efficacious territorial prevention and detection of an elevated percentage of likely non-symptomatic carriers.

Liver immunolocalization and plasma levels of MMP-9 in non-alcoholic steatohepatitis (NASH) and hepatitis C infection

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease. Many issues related to the pathogenesis of this disease remain unresolved. Because of NASH association with the activation of liver fibrogenesis, we examined the plasma levels and liver immunolocalization of matrix metalloprotease-9 (MMP-9), a molecule involved in the remodelling processes of fibrogenesis. In addition, patients with chronic hepatitis C (HCV) were analyzed. Plasma concentrations of MMP-9 were determined by ELISA from peripheral blood and immunohistochemistry of the same protein was carried out in formalin-fixed and paraffin wax-embedded liver specimens. The mean value of circulating concentrations of MMP-9 in healthy controls was 39.7 ng/ml (SD: +/-4.6). In NASH and HCV-infected patients, MMP-9 concentrations were higher: 69.0 ng/ml (SD: +/-14.5) and 61.7 ng/ml (SD: +/-11.0), respectively. In NASH livers, MMP-9 was mainly immunolocalized on neutrophils, whereas in HVC-infected livers it was mainly localized over biliary canaliculi, bile ducts and hepatocyte cytoplasm. The different MMP-9 immunolocalization patterns in the examined diseases suggest the presence of a different pathophysiological involvement of this protease in the fibrogenesis underlying these diseases.

A case of progression from type II cryoglobulinaemia to Waldenstrom's macroglobulinaemia in a patient with chronic hepatitis C.

Hepatitis C infection is associated with B-cell lymphoproliferative disorders, including mixed cryoglobulinaemia and B-cell lymphoma. A direct pathogenetic role of this infection in lymphomagenesis has been suggested but the molecular basis for viral induced B-cell proliferation is still unknown. We report an unusual case of a patient affected by chronic hepatitis C who presented severe type II cryoglobulinaemia and subsequently lymphoplasmacytoid lymphoma consistent with Waldenstrom’s macroglobulinaemia and type I cryoglobulinaemia. In this patient antiviral treatment induced beneficial effects.

Role of Ademetionine (S-Adenosylmethionine) in Cyclosporin-Induced Cholestasis

AbstractObjective: To determine the efficacy of ademetionine (S-adenosylmethionine, SAME) administration in preventing hepatotoxicity in patients undergoing long-term cyclosporin treatment. Design: Randomised, controlled, double-blind trial followed up for 3 months. Setting: Subjects were studied for a period of 10 days in hospital and then followed up in the outpatient unit for 3 months. Patients: 72 male patients with psoriasis, of whom 36 were treated with cyclosporin and 36 with cyclosporin plus ademetionine. Interventions: Cyclosporin treatment alone (10 mg/kg/day) was compared with treatment with the same dosage of cyclosporin in combination with ademetionine 400 mg/day. Main outcome measures: Serum fractioned bilirubin, γ-glutamyltransferase, alkaline phosphatase and transaminases, plasma malondialdehyde and 4-hydroxynonenal, and erythrocyte glutathione peroxidase were determined. Results: Hepatotoxicity and cholestasis were observed in 15 of 36 patients treated with cyclosporin alone, whereas no cases of liver cytotoxicity were observed in the group treated with cyclosporin in combination with ademetionine (p < 0.005). Moreover, the study results revealed a significant difference in oxidation-reduction balance between the two groups, with more marked oxidative stress in patients on cyclosporin alone. Conclusions: Ademetionine may protect the liver against potentially hepatotoxic substances, such as cyclosporin, and coadministration of ademetionine should therefore be considered when hepatotoxic drugs are used.

Immunolocalization of FOXP3 in HCV-infected liver biopsies. Preliminary observations.

Regulatory T cells (Tregs) represent a subset of T lymphocytes. This cell subpopulation plays an important role in controlling immune response as well as in inducing and maintaining immunologic tolerance [1]. The identification of this cell population in pathological condition, such as in hepatitis C virus (HCV) infected patients, may be useful for a better understanding of pathology.

A hyperdynamic portal syndrome with ascites after endoscopic laser treatment

Laser therapy has gained wide acceptance and application in many medical disciplines. Side effects of laser therapy are rare and the most frequent mainly involve the skin. We describe a patient affected by familial adenomatous polyposis that had been repeatedly controlled and treated endoscopically using an Nd:Yag laser. He presented with a progressive hyperdynamic portal syndrome with ascites caused by some arterovenous fistulas. We hypothesize that a rare side effect of the laser treatment may have caused ischemic and coagulative tissue inflammation that triggered off the pathological communications between the arterial and portal circulation.