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Biomedical subjects

M G Rumi

Publications and source records attributed to M G Rumi.

At least 19 recordsLinked to original sources

Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial.

The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.

Adolescent

The low risk of hepatitis C virus transmission among sexual partners of hepatitis C-infected hemophilic males: an international, multicenter study.

To study the transmission rate of hepatitis C virus (HCV) in the female sexual partners of antibody-positive hemophilic males, 106 partners from three hemophilia centers located in Europe, America, and Australia were tested for HCV seropositivity using a first-generation enzyme-linked immunosorbent assay (ELISA-1) and, subsequently, a second-generation ELISA (ELISA-2) and a supplemental recombinant immunoblot assay. Additionally, the cohort was tested for the presence of antibody to the human immunodeficiency virus type-1 and hepatitis B virus markers. No female partner was HCV antibody-positive using the ELISA-1 test, whereas five were seropositive by the ELISA-2 test. Three of these five female partners were seropositive on the supplemental test, the remaining two having indeterminate results, for an overall prevalence of 2.7%. Thus, even with the use of sensitive testing, the prevalence of HCV infection remains low in this cohort, showing that the efficiency of heterosexual transmission of HCV is poor.

Enzyme-Linked Immunosorbent Assay

Hepatitis C virus and hepatocellular carcinoma.

Epidemiological, clinical and laboratory data point to a role of hepatitis C virus infection in hepatocellular carcinoma. The connection appears to be indirect and to be mediated by cirrhosis. Thus, geographical differences can be observed, based on the locally prevalent etiological factors for cirrhosis. In the end, prospective studies of hepatitis C virus infected persons will be needed to elucidate the role of this agent in liver cancer.

Animals

Development of antibody to hepatitis C virus (HCV) in acute and chronic non-A, non-B post-transfusion hepatitis.

The antibody to hepatitis C virus (anti-HCV) was measured by an immunoassay in 507 serum samples from 94 patients with acute and chronic post-transfusion non-A, non-B hepatitis (NANB) and in 436 healthy blood donors. Anti-HCV was found in 70.8 of patients with acute hepatitis, in 78.2 with chronic hepatitis, and in 1.4 of healthy blood donors. In acute hepatitis, anti-HCV appeared in the serum from 4 to 34 weeks after transfusion and from 1 to 30 weeks after the onset of the overt disease. Three patients with resolving hepatitis (21%) and 2 who developed chronic hepatitis (10%) lost anti-HCV during a mean follow-up period of 28 months. Among the 36 patients with chronic hepatitis, 2 (6%) lost anti-HCV after 12 months and 8 years respectively. These data indicate that in recent years HCV has been the major etiologic agent of acute and chronic transfusion-associated hepatitis (TAH) in our geographical area. The late appearance of anti-HCV from the onset of clinical and biochemical signs of acute hepatitis in more than 70% of patients limits the diagnostic utility of this assay for an earlier serological diagnosis of acute NANB hepatitis. Additional studies are required to determine the diagnostic significance of this antibody in chronic NANB hepatitis.

Adult

Renal transplant recipients and chronic liver disease: statistical evaluation of predisposing factors.

278 azathioprine and methylprednisolone (AZA)-treated and 406 ciclosporin (CS) treated patients with a kidney graft functioning for more than 1 year were investigated for the presence of chronic liver disease (CLD), defined as an increase in transaminases of 1.5 times the upper normal limits for a period of at least 12 months. The prevalence of CLD was 36 and 27% in the two groups, respectively. The univariate analysis showed that male sex, alcohol abuse and HBsAg positivity correlated with CLD onset in the AZA group while blood transfusions, length of dialysis treatment, pretransplantation CLD, HBsAg positivity and ferritin levels over 800 ng/ml correlated with CLD onset in CS. The multivariate analysis identified male sex and HBsAg positivity in the AZA group and age over 18 years, high ferritin levels and HBsAg positivity in the CS group as risk factors predictive of CLD onset. Liver failure represented the 4th cause of death in the AZA group but 1 of the 2 most important causes of death in CS in the long term. However, these drawbacks were overcome by the overall low mortality rate in CS. Therefore, renal transplantation should not be refused to patients positive for HBsAg and/or with preexisting liver disease.

Adult

Hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma.

Hepatitis C virus (HCV) is the major etiologic agent of parenterally transmitted non-A, non-B hepatitis. To determine whether there is a relationship between this virus agent and hepatocellular carcinoma (HCC), the sera of patients with HCC and chronic hepatitis were assessed using a sensitive immunoassay for HCV antibody. Anti-HCV was detected in 65% of 132 patients with HCC, without any relationship with the presence of the hepatitis B surface antigen (HBsAg). The prevalence (74%) of anti-HCV was high, as expected in patients with putative non-A, non-B cirrhosis also. The prevalence of anti-HCV was less in patients with HBsAg-positive cirrhosis (28%) and in patients with disease not related to viral hepatitis and healthy controls (8%). These data suggest, but do not prove, that HCV is an important factor associated with HCC.

Carcinoma, Hepatocellular

Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients.

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.

Adolescent

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children.

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.

Adolescent

Acute hepatitis B in children with papular acrodermatitis.

Thirteen children who had repeated liver biopsies over a period of 2-16 years after the onset of papular acrodermatitis (PAC) were studied retrospectively. Six patients, rebiopsied within 36 months after the onset of PAC, had histologic evidence of chronic periportal hepatitis. However, repeated biopsies in 3 of the patients revealed a normal liver or chronic portal hepatitis. Whereas all patients had at the end of the observation markers of hepatitis B virus infection, 8 of the 10 patients studied had HBs antigenemia. These data indicate that severe active liver disease may regress without treatment in patients who have had PAC. However, the high frequency of a chronic HBsAg-carrier state among these patients suggests either an inefficient clearance of the virus or an altered immune reaction.

Acrodermatitis

The significance of protein C antigen in acute and chronic liver biliary disease.

Protein C, a naturally occurring inhibitor of blood coagulation, was measured immunologically in 160 patients with acute and chronic liver and biliary disease. In 31 patients with acute viral hepatitis serially studied from admission to discharge from hospital, protein C antigen (PC:Ag) was low on admission in a high proportion of cases (61%) but became normal in 90% of them after two weeks at a time when the prothrombin time was still prolonged in 46% of the cases. PC:Ag was also low in 25 cirrhotic patients and in 20 patients with chronic active hepatitis. In chronic hepatitis and cirrhosis, PC:Ag levels significantly correlated with indexes of liver synthetic function. In primary biliary cirrhosis (n:40), PC:Ag was low in patients with advanced disease (stages III-IV) but high in the early phases, when cholestasis was not yet accompanied by impaired protein synthesis. PC:Ag was also very high in 20 patients with large bile duct obstruction and highly correlated with indexes of cholestasis. The authors' findings indicate that PC:Ag is reduced in liver disease proportionally to the impairment of the liver synthetic function and that its normalization after acute hepatitis might represent an early marker of recovery of this function.

Acute Disease

Hepatocellular carcinoma in Italy: report of a clinical trial with intravenous doxorubicin.

Sixty-six patients with hepatocellular carcinoma (HCC) in various stages of hepatic involvement were studied prospectively. Of these, 50 (75%) had associated cirrhosis and 19 (28%) had serum hepatitis B surface antigen (HBsAg). Six (9%) patients were eligible for tumor resection, 34 were selected for doxorubicin chemotherapy (60 mg/m2, i.v., given every 3 weeks, up to a maximum dose of 550 mg/m2), and 26 were followed up without treatment. Untreated patients survived 1-18 months (median 1) after diagnosis. Surgically treated patients survived 1-14 months (median 4.5). In the doxorubicin group, six patients died soon after the first course of treatment, leaving 28 patients to be evaluated. Seven (24.5%) responded to therapy, surviving 2-26 months (median 8.0). Twenty-one (75.5%) did not respond to chemotherapy and had a median survival of 3.5 months (range: 2-12). Initial performance status and the degree of hepatic impairment were found to be covariates of prognostic significance. The type and severity of drug-related side-effects appeared to be comparable to those reported by others. In accordance with previous reports, our patients with HCC often had non-resectable tumors or responded poorly to chemotherapy. The association between this tumor and cirrhosis might partially account for treatment failure.

Adult

Decrease in suppressor/cytotoxic T-cells with histamine receptors in patients with chronic active hepatitis.

A fluorescence assay was employed to measure the levels of circulating suppressor/cytotoxic T cells with membrane receptors for histamine (H+T cells) in 33 patients with chronic active hepatitis, in seven patients with metabolic and vascular liver disorders and in 25 healthy individuals. The H+T cells were decreased in patients with CAH (4.6 +/- 2.2 cells/mm3 vs 16 +/- 3.9 cells/mm3; p less than 0.001), but were normal in patients with metabolic or vascular liver diseases (17.6 +/- 6 cells/mm3 vs 16 +/- 3.9 cells/mm3; NS). Patients with HBsAg-negative CAH had fewer circulating H+T cells than those with HBsAg-positive CAH (p less than 0.05). The same was true for patients with cirrhosis as compared to those without. The lymphocyte alterations were independent of the nature and course of CAH, but correlated inversely with the serum levels of gammaglobulins and with the histological features of hepatic inflammation (p less than 0.05). Like other sets of lymphocytes, the H+T cells in CAH may have locally either immunomodulatory or cytotoxic effects. In analogy with other immune disorders (histiocytosis X, atopic dermatitis), one might speculate that the alterations in H+T cells in CAH represent derangement of the immunoregulatory cell network. The absence of systemic features of autoimmunity in viral CAH correlates with the demonstration that H + T cells exert their immunoregulatory effects at the sites of inflammation where histamine is being released.

Adolescent