Gianfranca Stornaiuolo

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.

Temporal relationship between the appearance of thyroid autoantibodies and development of destructive thyroiditis in patients undergoing treatment with two different type-1 interferons for HCV-related chronic hepatitis: A prospective study

In this prospective study we performed repeated evaluations of thyroid status in patients undergoing treatment with different preparations of recombinant interferons (IFNs), in order to identify early markers of thyroid dysfunction. Moreover, we aimed to investigate whether the development of thyroid dysfunction was related to the appearance of thyroid autoimmunity. Our study included 51 consecutive patients without pre-existing thyroid disease, admitted to our hospital for Hepatitis C virus (HCV)- related chronic hepatitis. Thirty-six patients (Gr. A) were treated with IFN-α 2b plus ribavirin (RIBA), whereas 15 patients (Gr. B) underwent treatment with IFN-αcon-1 (CIFN) plus RIBA. Thyroid autoimmunity and function were prospectively evaluated before, every month during treatment and for 6 months after IFN withdrawal. At study entry, all patients were euthyroid and negative for thyroid autoantibodies. In Gr. A, 10 patients developed thyroid autoimmunity after a median period of 3 months (range: 1–6) treatment with IFN-α+RIBA. At the time of appearance of thyroid autoantibodies, 4 patients developed destructive thyrotoxicosis (overt in one case, subclinical in 3 cases), while other 4 patients showed a high reduction of serum TSH levels (median decrease: − 75.7%, range: −61.9- −84.2), which reached the low values of normal range. After a median period of 2 months (range: 1–3) from these biochemical abnormalities, 6 patients continuing antiviral treatment developed hypothyroidism (overt in 3 cases and subclinical in the other 3). In Gr. B, 5 patients developed thyroid autoimmunity after a median period of 3 months (range: 2–10) of treatment with CIFN+RIBA. Soon after the appearance of thyroid autoantibodies, all patients developed an overt thyrotoxicosis (with hyperthyroidism in 2 cases). Antiviral treatment was discontinued in all 5 cases. Thereafter, thyroid function recovered spontaneously without significant modifications of serum TGAb and TPOAb levels until the end of the study. In conclusion our prospective study demonstrated that: 1) the appearance of thyroid autoantibodies during treatment with IFN was accompanied in most cases by the occurrence of a destructive process in the thyroid gland; 2) The clinical expression of destructive thyroiditis was more evident in patients treated with CIFN than that in patients treated with IFN; 3) The thyroid clinical outcome of these patients was strictly correlated to the continuation of cytokine treatment.

Influenza vaccination in patients with cirrhosis and in liver transplant recipients.

To assess the safety and immunogenicity of influenza vaccination, patients with cirrhosis undergoing treatment or not and liver transplant recipients under standard immunosuppression were vaccinated and followed up for 6 months. One month after vaccination, seroprotection rates and antibody GMTs against the three vaccine antigens were higher than baseline levels in all three patients groups. No differences in seroconversion and seroprotection rates were found within groups, but antibody GMTs against A/H1N1 and A/H3N2 strains were lower in liver transplant recipients than in patients with cirrhosis without treatment. No serious adverse events and no alteration of the liver function tests were observed. Patients with cirrhosis, including those under treatment, and liver transplant recipients benefit from influenza vaccination and can be safely immunized.

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.

Visceral leishmaniasis causes fever and decompensation in patients with cirrhosis

Infections and fever due to bacterial infections are well-known complications of liver cirrhosis, and often trigger decompensation and death.1 Visceral leishmaniasis (VL), a protozoan infection endemic in the Mediterranean area, causes a febrile disease, the clinical and laboratory features (splenomegaly, pancytopenia, reduced serum albumin and increased γ-globulin concentrations) of which largely overlap with those of cirrhosis.2,3 Although the areas where VL is endemic coincide with areas where the prevalence of cirrhosis is high, no study has described VL in patients with cirrhosis. During a 12-year period, all patients with cirrhosis admitted for decompensation and fever lasting more than 1 week, unresponsive to broad-spectrum antibiotics, underwent diagnostic procedures for VL. For each case diagnosed as VL, three consecutive cases of bacterial infection observed in the same period were enrolled. Cirrhosis was defined …

Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis

BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated.AIM: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy.PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologicallyMETHODS: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis.RESULTS: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0% vs 58.7%, P= 0.03), had lower transaminase levels (3.3 ± 2.0 vs 3.8 ± 2.5 u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3% vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34–2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41–2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69–1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76–1.95).CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.

Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV‐related liver cirrhosis

objective The aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV‐related liver cirrhosis.

Active recruitment strategy in disadvantaged immigrant populations improves the identification of human immunodeficiency but not of hepatitis B or C virus infections

BACKGROUND Barriers to access medical screening and care may underestimate the number of diseased subjects among immigrant populations. AIMS To evaluate the prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infections among immigrants recruited in a disadvantaged area. METHODS The study enrolled all subjects seen between 1999 and 2009 at an on-site health and family counselling centre for immigrants. During the first 6 years of the study a pro-active recruitment was performed using a mobile unit. RESULTS Overall 2681 subjects were enrolled (median age: 31 years; 52.8% males; 82.3% from Sub-Saharan Africa; 13.9% of the women were sex workers). A total of 206 subjects (7.6%) were hepatitis B surface antigen-positive, 84 (3.6%) were anti-hepatitis C virus-positive, 129 (5%) were anti-human immunodeficiency virus-positive, 84 (3.1%) were drug users, and 436 (16.3%) were alcohol abusers. The prevalence of hepatitis B surface antigen and anti-hepatitis C virus remained consistent throughout the study period, while the prevalence of human immunodeficiency virus significantly decreased. At multivariate analysis, hepatitis B virus infection was associated with male gender, hepatitis C virus infection with drug addiction, and human immunodeficiency virus infection was associated with female gender, drug addiction, and active recruitment. CONCLUSIONS An active recruitment strategy should be considered to reach disadvantaged populations at high risk of human immunodeficiency virus infection.

Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis

Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis.

Interferon-Free Regimens in Hepatitis B Surface Antigen/Anti–Hepatitis C Virus Positive Patients: The Need to Control Hepatitis B Virus Replication to Avoid Hepatitis B Virus Reactivation

Interferon-Free Regimens in Hepatitis B Surface Antigen/Anti–Hepatitis C Virus Positive Patients: The Need to Control Hepatitis B Virus Replication to Avoid Hepatitis B Virus Reactivation Margherita Macera,* Maria Stanzione,* Vincenzo Messina, Giuseppe D’Adamo, Vincenzo Sangiovanni,k Lucia Mioglioresi, Luca Fontanella, Stefania De Pascalis,* Gianfranca Stornaiuolo,* Alfonso Galeota Lanza,** Tiziana Ascione, Evangelista Sagnelli,* Ivan Gentile, Guido Piai, Giovanni Battista Gaeta,* and Nicola Coppola*