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Treatment of chronic hepatitis B in children with prednisone followed by alfa-interferon: a controlled randomized study.

The efficacy and safety of sequential treatment with prednisone and interferon was evaluated in a randomized, controlled study on 43 children with biopsy proven HBsAg/HBeAg/hepatitis B virus-DNA positive, anti-delta negative, chronic hepatitis (34 chronic persistent hepatitis, 9 chronic active hepatitis). Patients received either a 1-month course of prednisone (0.6 to 0.3 mg/kg per day) followed by interferon alfa-2a (3 MU/m2, thrice weekly, for 12 months; 22 patients) or no treatment (21 patients). At the end of the study (20 months), clearance of hepatitis B virus-DNA and HBeAg seroconversion were observed in nine (41%) of the patients treated with prednisone and interferon and in two (9.5%) of the untreated controls (p = 0.020). Two of the treated patients who lost HBeAg, also cleared HBsAg. In the treated group, 13 (59%) patients had stable normal levels of alanine aminotransferase on their last examination. The baseline serum level of hepatitis B virus-DNA was an important predictor of response. In fact, HBeAg clearance was observed in 75% of patients with a baseline hepatitis B virus-DNA level lower than 100 pg/ml and in none with a level above 100 pg/ml. We suggest that combined treatment with prednisone followed by alfa-interferon may be safe and effective in inducing a stable clearance of HBeAg and, in some cases, of HBsAg in children with chronic hepatitis B and with a low level of viral replication. For children with high levels of viral replication, this regimen seems to be ineffective.

Hepatitis C virus infection in households of anti-HCV chronic carriers in Italy: A multicentre case-control study

To test the hypothesis that households of anti-HCV positive subjects might be at increased risk of HCV infection, a case-control study was carried out comparing 518 family members of 205 anti-HCV positive subjects (index carriers) with 281 family members of 100 anti-HCV negative subjects (index controls), consecutively observed in ten gastroenterology units in different Italian regions. The index carriers were age and sex matched to the index controls and their households were similar with respect to the main sociodemographic characteristics. Anti-HCV antibodies were found in 6.9% (36/518) of household members of index carriers and in 3.2% (9/281) of household members of index controls (p<0.05). The results of multiple logistic regression analysis showed that being over 50 years of age was the sole independent predictor for a household contact of the likelihood of being anti-HCV positive (O.R. 3.6; C.I. 95%=1.5−8.2). Being in the household of an anti-HCV index carrier was marginally associated to anti-HCV positivity (O.R. 2.0; C.I. 95%=0.9−4.6). No association was found for sex, area of residence, family size, lowest level of schooling, or any type of family relationship. These findings are not in compliance with the statement that household contacts of HCV carriers are at increased risk of HCV infection. The 3.2% anti-HCV prevalence rate observed among household contacts of anti-HCV negative index controls may suggest that the true anti-HCV prevalence in the general population in Italy is nearly 2.5 times as high as the 1.3% found in Italian blood donors.SummaryTo test the hypothesis that households of anti-HCV positive subjects might be at increased risk of HCV infection, a case-control study was carried out comparing 518 family members of 205 anti-HCV positive subjects (index carriers) with 281 family members of 100 anti-HCV negative subjects (index controls), consecutively observed in ten gastroenterology units in different Italian regions. The index carriers were age and sex matched to the index controls and their households were similar with respect to the main sociodemographic characteristics. Anti-HCV antibodies were found in 6.9% (36/518) of household members of index carriers and in 3.2% (9/281) of household members of index controls (p<0.05). The results of multiple logistic regression analysis showed that being over 50 years of age was the sole independent predictor for a household contact of the likelihood of being anti-HCV positive (O.R. 3.6; C.I. 95%=1.5−8.2). Being in the household of an anti-HCV index carrier was marginally associated to anti-HCV positivity (O.R. 2.0; C.I. 95%=0.9−4.6). No association was found for sex, area of residence, family size, lowest level of schooling, or any type of family relationship. These findings are not in compliance with the statement that household contacts of HCV carriers are at increased risk of HCV infection. The 3.2% anti-HCV prevalence rate observed among household contacts of anti-HCV negative index controls may suggest that the true anti-HCV prevalence in the general population in Italy is nearly 2.5 times as high as the 1.3% found in Italian blood donors.

Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey

Aims  To conduct a multicentre observational study to describe management of foot infections in diabetes in the out‐patient setting in Italy.

Efficacy of Amphotericin B Colloidal Dispersion in the Treatment of Mediterranean Visceral Leishmaniasis in Immunocompetent Adult Patients

Twelve immunocompetent adults with Mediterranean visceral leishmaniasis (VL) were treated with amphotericin B colloidal dispersion (ABCD; 2 mg/kg/d for 7 d). All patients showed rapid clinical response without significant adverse events. Two weeks after therapy they were parasitologically cured and no relapses occurred during 6 months. ABCD is a valid alternative in the management of Mediterranean VL in adult patients.Twelve immunocompetent adults with Mediterranean visceral leishmaniasis (VL) were treated with amphotericin B colloidal dispersion (ABCD; 2 mg/kg/d for 7 d). All patients showed rapid clinical response without significant adverse events. Two weeks after therapy they were parasitologically cured and no relapses occurred during 6 months. ABCD is a valid alternative in the management of Mediterranean VL in adult patients.

Multiple hepatitis virus infections in chronic HBsAg carriers in Naples

SummaryIn order to determine the prevalence of multiple infections with hepatitis viruses in chronic HBsAg carriers in Naples, to assess the interaction between HBV, HDV and HCV infections and to evaluate the influence of multiple virus hepatitis infections on the clinical presentation, we studied 198 HBsAg chronic carriers observed consecutively from 1971 to 1988 at our Liver Unit. Of the 198 HBsAg chronic carriers, 171 had undergone percutaneous liver biopsy. The presence of HBcAg or HDAg in the liver biopsy was considered a marker of HBV or HDV replication, respectively; the presence of anti-HCV was considered a marker of HCV infection. Anti-HCV was observed in 13.6% of the 22 subjects with normal liver, in 27.7% of the 47 patients with minimal chronic hepatitis, in 40% of the 50 with mild chronic hepatitis, in 70.6% of the 17 with moderate hepatitis, in 66.7% of the 3 with severe chronic hepatitis and in 65.6% of the 32 with active cirrhosis. Anti-HCV positive cases were antiHD positive more frequently than the anti-HCV negative (59.2% vs. 43%, p=0.05). HDV infection exerted a clear inhibition on the HBV genome. Among the 171 HBsAg chronic carriers, the finding of an active chronic hepatitis (moderate chronic hepatitis+severe chronic hepatitis+active cirrhosis) is less frequent in subjects with HBV replication alone than in those with HDV replication or HCV infection. Patients with both HBV replication and HCV infection and those with both HDV replication and HCV infection showed a very high prevelance of active chronic hepatitis.

Interaction between HDV and HBV infection in HBsAg-chronic carriers

SummaryWe studied the interaction between HBV and HDV infection in 149 consecutive subjects with HBsAg positive chronic hepatitis and in 22 chronic HBsAg healthy carriers. Liver HBcAg was detected in 52 (30.4%) of the 171 subjects. Of these 52, 35 were HBV-DNA and HBeAg positive, 11 HBV-DNA positive only; two HBeAg positive only and four were negative for both HBeAg and HBV-DNA. None of the 119 HBcAg-negative subjects had detectable HBV-DNA in serum. HD-Ag in hepatocytes was detected in 31 of the 171 subjects (18%); it was detectable in none of the 22 HBsAg healthy carriers, in four of the 56 patients with chronic persistent hepatitis (7.2%), in six of the 24 patients with chronic lobular hepatitis (25%), in 16 of the 40 patients with chronic active hepatitis (40%) and in five of the 29 with cirrhosis (17%). A presence of anti-HD in serum in the absence of liver HD-Ag was found in 54 of the 171 subjects (32%). This condition was observed not only in patients with a progressive disease (37.7% of chronic active hepatitis or cirrhosis and 33% of chronic lobular hepatitis), but also in healthy carriers (36%) and in chronic persistent hepatitis patients (21.4%). Liver HBcAg was detected in 6.4% of the 31 HD-Ag-positive patients, in 12.9% of the 54 HD-Ag-negative/anti-HD positive, but in 50% of the 86 with no marker of HDV infection. HDV appears to inhibit HBV genome and such inhibition may persist even when anti-HD is the only HDV marker detectable.ZusammenfassungBei 149 nacheinander eingewiesenen chronischen HBsAg-positiven Patienten mit chronischer Hepatitis und 22 gesunden HBsAg Trägern wurde die Interaktion zwischen der HBV- und HDV-Infektion untersucht. Bei 52 der insgesamt 171 Personen (30,4%) fand sich HBsAg in den Leberzellen. Bei 35 dieser 52 Fälle wurde HBV-DNA und HBeAg nachgewiesen, in 11 Fällen HBV-DNA allein. Bei den 119 HBcAg-negativen Personen waren HBV-DNA in keinem Fall im Serum nachweisbar. Bei 31 der 171 Personen wurden HD-Ag in Hepatozyten entdeckt (18%). Die 22 gesunden HBsAg-Träger waren alle HD-Ag negativ. Von den 56 Patienten mit chronisch persistierender Hepatitis waren vier positiv (7,2%); von den 24 Patienten mit chronischer lobulärer Hepatitis sechs (25%), von den 40 Patienten mit chronisch aktiver Hepatitis 16 (40%) und von den 29 Patienten mit Zirrhose fünf (17%). 54 der 171 Untersuchten (32%) wiesen im Serum anti-HD auf, ohne daß sich HD- Ag in der Leber nachweisen ließ. Dabei handelte es sich nicht nur um Patienten mit progressivem Krankheitsverlauf (37,7% der Patienten mit chronisch aktiver Hepatitis und 33% derer mit chronischer lobulärer Hepatitis) sondern auch um gesunde Träger (36%) und Patienten mit chronisch persistierender Hepatitis (21,4%). Bei 6,4% der 31 HD-Ag positiven Patienten ließ sich HBcAg in der Leber nachweisen; positiv waren auch 12,9% der 54 HD-Ag-Negativ/anti-HD-Positiven und 50% der Personen ohne Marker für eine HDV-Infektion. Offensichtlich hemmt HDV das HBV-Genom; diese Hemmwirkung kann bestehen bleiben, auch wenn anti-HD der einzige nachweisbare Marker für eine durchgemachte HDV-Infektion ist.

Non responders to interferon therapy among chronic hepatitis patients infected with hepatitis C virus

We studied a series of 268 chronic hepatitis C patients (31 chronic persistent hepatitis CPH, 69 mild chronic active hepatitis CAH, 125 severe CAH, and 43 active cirrhosis) enrolled from 1988 to 1991 in different therapeutic protocols using lymphoblastoid or recombinant interferon (IFN) at a dosage of 3 mega units (M.U.), three times a week for 12 months. Of these patients 54.8% showed a complete response (normalization of aminotransferases), 14.2% a partial response (decrease in aminotransferases of over 50%), 27.6% no response, and 3.4% a substantial progressive increase in the liver enzymes during IFN (becoming worse). The prevalence of non responders was lower in CPH (9.7%) than in CAH patients (31.9% in the mild form and 20.8% in the severe), and significantly higher in patients with cirrhosis (53.5%). No correlation was observed between non response and the baseline aminotransferase level or the patients sex. Patients under 35 had a better response to IFN when compared with patients 36-50 years. This is probably due to the higher prevalence of CPH patients with a good response to IFN in the youngest group. No effect was gained in non responders by increasing the dose or shifting from recombinant to lymphoblastoid IFN; three patients were then treated with steroids, but only one benefitted. For 5 of the 9 patients who became worse, steroids were started after discontinuation of IFN therapy, and they induced a favorable response only for the 3 who had developed autoantibodies during IFN treatment.

Clinical expression of 'silent' hepatitis B virus infection in a patient with visceral leishmaniasis.

A 69-year-old male was hospitalized in January 1999 because of viszeral leishmaniasis. He had also suffered from anti-hepatitis C virus (HCV)-positive chronic hepatitis for years. All serum hepatitis B virus (HBV) antigens and antibodies were negative except for anti-HBc. The patient was treated with amphotericin B cholesteryl sulfate (2 mg/kg twice a day for 7 days, iv). Fever disappeared on the 3rd day of treatment, the clinical condition improved rapidly and the patient recovered.In May 1999 the patient developed iteric HBsAg-negative acute hepatitis (aspartate aminotransferase 722 U/l; alanine aminotransferase 988 U/l). Anti-HBc IgM was positive and HBV-DNA was detected in serum by PCR. Anti-HAV IgM was negative. A serum sample obtained on presentation and stored at −80°C was retrospectively tested and found positive for HBV-DNA. In July 1999, complete remission of acute hepatitis and seroconversion to anti-HBs was observed.We suppose that a moderate depression of the immune system, probably associated with leishmaniasis, may have enhanced HBV replication in the patient who had an HBsAg-negative ‘silent’ HBV infection. Restoration of the immune system after successful antiprotozoan therapy might have induced cell-mediated necrosis of the HBV-infected hepatocytes and seroconversion to anti-HBs.

Effect of prednisone priming followed by alfa-interferon in treatment of children with chronic hepatitis B: an interim analysis of a controlled trial.

A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity.

Azathioprine treatment in a patient with HBsAg-positive acute viral hepatitis complicated by bridging necrosis

SummaryA patient with HBsAg-positive subacute hepatitis who presented a progressively deteriorating clinical condition was treated with azathioprine (100 mg/day) for eight months. Although the clinical symptoms disappeared and the biochemical abnormalities decreased, the disease nevertheless progressed to chronic active hepatitis. Moreover, azathioprine favoured hepatitis B virus replication since titers of HBsAg, HBeAg and Dane-particle-associated coreantigen, as detected by radioimmunoassay, increased during treatment. In all, this drug was only of moderate use to our patient.ZusammenfassungEin Patient mit HBsAg-positiver, subakuter Hepatitis und progressiver klinischer Verschlechterung wurde acht Monate lang mit 100 mg/Tag Azathioprin behandelt. Obwohl die klinischen Symptome verschwanden und sich die biochemischen Parameter besserten, ging die Erkrankung in eine chronisch aktive Hepatitis über. Daneben begünstigte Azathioprin die Hepatitis-B-Virus-Replikation, denn die im Radioimmunoassay bestimmten Titer von HBsAg, HBeAg und Dane-Partikel-assoziiertem Core Antigen stiegen unter der Behandlung an. Insgesamt war das Medikament nur von mäßigem Nutzen für den Patienten.