Multiple viral infections.

Individuals at risk of HIV are concomitantly at risk of acquiring parenterally or sexually transmitted viruses. Multiple hepatitis co-infection (HBV+HCV; HBV+HDV; HBV+HDV+HCV) has not been systematically sought after in the large cohorts of HIV-infected patients, but has been reported in 0.4% to more than 50% of patients. HIV-infected patients with multiple hepatitis have a higher rate of liver-related morbidity and mortality than patients with HIV infection alone or with a single hepatitis co-infection. The degree of immunodepression is an important factor in liver disease progression. Since GBV-C virus is transmitted parenterally or by sexual contact, a high prevalence was found in chronic hepatitis C and in HIV-infected patients. Patients with multiple hepatitis have been excluded from randomised therapeutic trials of viral hepatitis in HIV-infected and HIV-negative patients. Thus, the therapeutic approach is based on the results of a small series and empirically oriented toward the prevailing infection. HIV-infected patients should be tested for hepatitis B, C and D systematically and hepatitis B vaccination should be considered for those with HCV co-infection and absence of HBV markers. Studies are needed to assess treatment strategies.

Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study.

BACKGROUND/AIMS: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. METHODS: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units. RESULTS: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both. CONCLUSIONS: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.

Risk factors for "major" embolic events in hospitalized patients with infective endocarditis.

BACKGROUND: Infective endocarditis often is complicated by embolic events after hospital admission. Identifying patients at higher risk may improve the disease outcome. This study was aimed at identifying predictors of embolic risk among the clinical and laboratory data obtained on hospital admission in patients diagnosed as having definite infective endocarditis according to the Duke criteria. METHODS: Ninety-four patients were enrolled in a prospective study. The results of hematologic, echocardiographic, and microbiological investigations were analyzed, using statistical methods as appropriate. Multivariate analysis was applied to variables significantly associated with embolism in univariate analysis. RESULTS: Forty-six percent of patients had a major embolic complication after admission. No association was found between embolism and sex, site of infection, or microorganism involved. Patients with embolism were significantly younger, had larger vegetation, and showed a significantly higher level of serum C-reactive protein and lower albumin concentrations than those without embolism. Young age, larger vegetation size, and high levels of C-reactive protein were the independent variables associated with an increased incidence of embolic events in the multivariate logistic regression analysis. CONCLUSIONS: Our data indicate that patients with infective endocarditis with young age and/or with large vegetation and/or with high serum levels of C-reactive protein are at increased risk of major embolic complications during the in-hospital course of the disease.

Case report: effect of antileishmanial treatment on hepatitis C viraemia in a visceral leishmaniasis patient with chronic hepatitis C.

We describe a case of Mediterranean visceral leishmaniasis (VL) in a patient with pre-existing chronic hepatitis C, which caused high hepatitis C virus (HCV) plasma concentration and was followed by a rapidly growing hepatocellular carcinoma (HCC). The high HCV load was drastically and persistently reduced soon after treatment with liposomal amphotericin B suggesting a cause-effect interaction. Some data suggest that liposomal amphotericin B may have an immunomodulatory effect. VL may directly affect the liver function, but HCC has never been reported as a consequence of the disease. This case suggests that VL causes an increase in HCV replication, but, although the growth of the HCC can be defined as exceptional, a relationship with VL is not proven.

Immunogenicity and safety of an adjuvanted influenza vaccine in patients with decompensated cirrhosis.

The immunogenicity and tolerability of an adjuvanted trivalent influenza vaccine was evaluated in 20 patients with cirrhosis due to chronic HBV or HCV infections and eight healthy age matched controls. Seroconversion or a four-fold or greater increase in HI antibody titres to each antigen occurred in 75-85% of the patients and in 100% of the controls. One month after vaccination, the geometric mean antibody titres were significantly higher than baseline in both groups of vaccinees. A mild and transient erythema at the inoculation site was the only side effect for both groups. The results justify the use of an adjuvanted influenza vaccine, given as single-dose, in patients with advanced liver disease.

Serum insulin-like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a prospective study.

BACKGROUND: Although experimental studies have demonstrated an important role of insulin-like growth factor I (IGF-I) in hepatocarcinogenesis, the clinical data about IGF-I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF-I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)-related cirrhosis. METHODS: One hundred fourteen consecutive patients with HCV-related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 +/- 12.0 months with ultrasound examinations of the liver and serum alpha-fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child-Pugh scoring system. Serum IGF-I levels were measured prospectively at the study entry and at least every 12 months throughout follow-up. RESULTS: Twenty patients (19.2%) developed HCC during follow-up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF-I concentrations did not modify significantly during follow-up. Conversely, in patients who developed HCC, IGF-I levels decreased significantly during follow-up (from 72.6 +/- 29.9 microg/L to 33.8 +/- 14.5 microg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF-I level preceded the diagnosis of HCC by 9.3 +/- 3.1 months. CONCLUSIONS: This prospective study demonstrates that, in patients with HCV-related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF-I levels independent of the grade of impairment of liver function; and 2) modification of the IGF-I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor.

Histological and virological features and follow-up of hepatitis C virus carriers with normal aminotransferase levels: the Italian prospective study of the asymptomatic C carriers (ISACC).

BACKGROUND/AIMS: To evaluate demographic characteristics, liver histology and virological features of hepatitis C virus (HCV) carriers with normal alanine transaminase (ALT) levels. METHODS: A nationwide prospective study was started in 1997. Four Italian centres have participated in this study. RESULTS: Eight hundred and eighty subjects entered the study. One hundred and eighty-nine (21.5%) were excluded during the follow-up because of ALT increase. Among the 691 patients with persistent ALT normality, 72% were females. An overall prevalence of genotype 2 was found (52%). Normal liver was found in 17% of the patients; 34% had minimal chronic hepatitis, 44% mild hepatitis, 4% moderate to severe hepatitis, and 1% had cirrhosis. Clinical and virological features did not differ between subjects with ALT flares and those with persistently normal ALT. Baseline ALT levels have no effects on liver histology and clinical outcome. CONCLUSIONS: Many HCV carriers have significant chronic liver damage, although in the majority of them liver lesions are minimal or mild. Up to 60% of HCV carriers in Italy harbour non-1 HCV types. Current definition of HCV carriers with persistently normal ALT levels, based upon three normal ALT values over a 6-month period, is not adequate to discriminate between carriers with persistent ALT normality and those with transient biochemical remission. Longer follow-ups are needed.