Augusto Andreana

Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis

The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r = −0·54; P < 0·0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0–2, lower in those with grade 3 (P < 0·008) and lowest in those with grade 4 (P < 0·05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P < 0·0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r = − 0·50; P < 0·0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0–1 and grade 4 respectively (P < 0·001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.

Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C.

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19–68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 × 106 eq/ml; range <0.2–69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (≥3 × 106 eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 × 106 eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels ≥3 × 106 eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels ≥3 × 106 eq/ml and grade 3–4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury.

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.

Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma. A Cancer of the Liver Italian Program (CLIP 08)retrospective case-control study

Background Patients with small hepatocellular carcinoma (HCC) are usually treated with hepatic resection or percutaneous ethanol injection (PEI). Goals To compare the effects of hepatic resection versus PEI on survival in a matched case–control study. Study Patients with single-nodule HCC (≤5 cm) who were treated with hepatic resection (cases) or PEI (controls) were eligible. Matching criteria were date of diagnosis, Child–Pugh stage, and age at diagnosis. Kaplan–Meier survival curve of the control group was drawn weighing each stratum by the inverse of its size. Treatments were compared by a stratified Coxs model, adjusted by CLIP score. Results Of 912 patients, 197 were eligible and 82 (17 cases and 65 controls) were matched, creating 17 strata. Nine (53%) cases and 41 (63%) controls died. Cox model showed no survival difference between the two groups; hazard ratio of PEI versus hepatic resection was 1.04 (95% CI = 0.43–2.52). One- and 3-year survival rates in the hepatic resection and PEI groups were 82% versus 91% and 63% versus 65%, respectively. Conclusions Patients with small HCC treated with hepatic resection or PEI have similar survival rates. In view of the higher cost and morbidity of hepatic resection, a prospective randomized study is warranted.

Interferon and ribavirin treatment for chronic hepatitis C may activate celiac disease.

to be the cause of hepatocyte damage, reinstitution of immunosuppression by administering corticosteroids has been proposed (4). The evidence of reactivation after fludarabine in our patient is based on positive HBsAg and high titre of HBV DNA, although liver function tests were normal. The combined treatment with corticosteroid and lamivudine prevented hepatic damage and suppressed HBV replication. We suggest monitoring of HBV DNA also in chemotherapyreceiving patients who had recovered from previous HBV infection. A combined therapy with corticosteroids and lamivudine can be considered in these patients, when reactivation of HBV infection is demonstrated.

HCV RNA levels in serum, liver, and peripheral blood mononuclear cells of chronic hepatitis C patients and their relationship to liver injury

Objective:We sought to evaluate the relationship between HCV RNA levels in serum, liver, and peripheral blood mononuclear cells (PBMC) and the degree of liver injury in chronic hepatitis C (CHC) patients.Methods:Thirty-six consecutive CHC patients were included in the study. The liver damage was evaluated by the histological activity index (HAI) score. The HCV RNA levels in the three compartments studied were assessed by bDNA assay. Nineteen patients were treated with α-interferon 2b (IFN).Results:Serum and liver HCV RNA levels in CHC patients were significantly associated with an increasing HAI score irrespective of the HCV genotypes. Cirrhotic patients showed higher HCV RNA levels than the CHC patients with HAI score 1–4 (p < 0.05), but had lower levels than the group with HAI score > 8 (p < 0.03). Patients with HAI score 1–4 showed the lowest levels of HCV RNA in PBMC. There was a strong relation (r = 0.78; p < 0.001) between serum and liver HCV RNA levels, but not between either serum or liver HCV RNA levels and those of PBMC. Seven patients showed a response to IFN and three of these had a sustained response. Pretreatment levels of HCV RNA in PBMC of the IFN responder patients were lower than those of the nonresponder patients (p < 0.02).Conclusions:The data indicate a relation between serum or liver HCV RNA levels and the degree of liver injury in CHC patients, and show that serum HCV RNA level mirrors the hepatic viral burden.

Successful treatment with ampicillin and fluoroquinolones of human endocarditis due to high-level gentamicin-resistant enterococci

Abstract Two cases of endocarditis, one caused by high-level gentamicin-resistant Enterococcus durans and the other by high-level gentamicin- and glycopeptide-resistant Enterococcus faecalis, successfully treated with a combination of ampicillin and a fluoroquinolone are reported. Both strains were susceptible to ampicillin. Enterococcus faecalis was susceptible to ciprofloxacin and to ofloxacin, but Enterococcus durans was moderately resistant to these agents. Microbiological and clinical cure was obtained with a 6-week course of ampicillin plus ciprofloxacin in one case and with ofloxacin in the second case due to intolerance to ciprofloxacin. The efficacy of the treatment was predicted in vitro by time-kill studies and by adequate serum bactericidal titres.

Visceral leishmaniasis during pregnancy treated with meglumine antimoniate

Data on the efficacy and safety of pentavalent antimony in the treatment of visceral leishmaniasis during pregnancy are scanty. A case of visceral leishmaniasis in a 39-year-old woman in the second trimester of pregnancy is reported here. The patient was hospitalized in poor condition with high fever and pancytopenia which had lasted for 6 weeks. A bone marrow aspirate revealed numerous amastigotes and serodiagnosis forLeishmania was positive at a high titer. The patient was successfully treated with meglumine anti-moniate at a daily dose of 850 mg of antimony for 20 days. She delivered at term a healthy female baby who remains in good condition at 18 months of age. Thus a dose of 850 mg of antimony, which is lower than that presently recommended, seems to be effective and non toxic to the fetus when administered at the second trimester of pregnancy. Zur Behandlung der Leishmaniasis mit pentavalenten Antimon in der Schwangerschaft liegen nur spärliche Daten vor. Bei einer 39 Jahre alten Frau trat im zweiten Schwangerschaftstrimester eine viszerale Leishmaniasis auf. Die Patientin wurde in schlechtem Zustand mit hohem Fieber und Panzytopenie, die schon über 6 Wochen bestanden hatten, stationär aufgenommen. Im Knochenmarkpunktat fanden sich zahlreiche Amastigoten, die Serodiagnose war hochtitrig-positiv fürLeishmania. Die Patientin wurde erfolgreich mit Meglumin Antimonat mit einer täglichen Dosis von 850 mg Antimon behandelt. Diese Dosis liegt unterhalb der derzeit empfohlenen Dosis, doch scheint sie wirksam und nicht fetotoxisch zu sein, wenn sie im zweiten Schwangerschaftstrimester verabreicht wird.SummaryData on the efficacy and safety of pentavalent antimony in the treatment of visceral leishmaniasis during pregnancy are scanty. A case of visceral leishmaniasis in a 39-year-old woman in the second trimester of pregnancy is reported here. The patient was hospitalized in poor condition with high fever and pancytopenia which had lasted for 6 weeks. A bone marrow aspirate revealed numerous amastigotes and serodiagnosis forLeishmania was positive at a high titer. The patient was successfully treated with meglumine anti-moniate at a daily dose of 850 mg of antimony for 20 days. She delivered at term a healthy female baby who remains in good condition at 18 months of age. Thus a dose of 850 mg of antimony, which is lower than that presently recommended, seems to be effective and non toxic to the fetus when administered at the second trimester of pregnancy.ZusammenfassungZur Behandlung der Leishmaniasis mit pentavalenten Antimon in der Schwangerschaft liegen nur spärliche Daten vor. Bei einer 39 Jahre alten Frau trat im zweiten Schwangerschaftstrimester eine viszerale Leishmaniasis auf. Die Patientin wurde in schlechtem Zustand mit hohem Fieber und Panzytopenie, die schon über 6 Wochen bestanden hatten, stationär aufgenommen. Im Knochenmarkpunktat fanden sich zahlreiche Amastigoten, die Serodiagnose war hochtitrig-positiv fürLeishmania. Die Patientin wurde erfolgreich mit Meglumin Antimonat mit einer täglichen Dosis von 850 mg Antimon behandelt. Diese Dosis liegt unterhalb der derzeit empfohlenen Dosis, doch scheint sie wirksam und nicht fetotoxisch zu sein, wenn sie im zweiten Schwangerschaftstrimester verabreicht wird.

Treatment of pulmonary nocardiosis in heart-transplant patients: importance of susceptibility studies

Pulmonary nocardiosis is an infrequent but insidious disease in transplant patients. It has occurred in our centre in 3 out of 233 heart‐transplant recipients since 1988. Common clinical features were mild symptoms and a severe nodular lung involvement. Early diagnosis was based upon cultures of bronchoalveolar lavage or fine‐needle aspirate specimens of the lung lesions. Susceptibility studies and tests of antibiotic synergism guided the therapy. Two patients were treated with a combination of piperacillin‐tazobactam and ciprofloxacin, and one with imipenem and amikacin, for 3–4 wk followed by a 3‐month course of trimethoprim‐sulphamethoxazole. The nocardial disease was successfully treated in the 3 patients; however, one died of subsequent invasive pulmonary aspergillosis. In the absence of consensus on the length of therapy, this experience suggests that a synergistic combination of a beta‐lactam/beta‐lactamase inhibitor with ciprofloxacin or amikacin followed by a short course of trimethoprim‐sulphamethoxazole may be effective in eradicating nocardial disease and may reduce the need for long‐term treatment.

Comparative activities of isepamicin, amikacin, cefepime, and ciprofloxacin alone or in combination with other antibiotics against Stenotrophomonas maltophilia.

1. Hirschtick RE, Glassroth J, Jordan MC, Wilcosky TC, Wallace JM, Kvale PA, Markowitz N, Rosen MJ, Mangura BT, Hopewell PC, and the Pulmonary Complications of HIV Infection Study Group: Bacterial pneumonia in persons infected with the human immunodeficiency virus. New England Journal of Medicine (1995) 333 :845–851 2. Caiaffa WT, Graham NMH, Vlahov D: Bacterial pneumonia in adult populations with human immunodeficiency virus (HIV) infection. American Journal of Epidemiology (1993) 138 :909–922 3. Shepp DH, Tang IT-L, Ramundo MB, Kaplan MH: Serious Pseudomonas aeruginosa infection in AIDS. Journal of Acquired Immune Deficiency Syndromes (1994) 7 :823–831 4. Schuster MG, Norris AH: Community-acquired Pseudomonas aeruginosa pneumonia in patients with HIV infection. AIDS (1994) 8 : 1437–1441 5. Mendelson MH, Gurtman A, Szabo S, Neibart E, Meyers BR, Policar M, Cheung TW, Lillienfeld D, Hammer G, Reddy S, Choi K, Hirschman SZ: Pseudomonas aeruginosa bacteremia in patients with AIDS. Clinical Infectious Diseases (1994) 18 :886–895 6. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. New England Journal of Medicine (1998) 338 :853–860 7. Niederman MS, Bass JB Jr, Campbell GD, Fein AM, Grossman RF, Mandell LA, Marrie TJ, Sarosi GA, Torres A, Yu VL: Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy. American Review of Respiratory Disease (1993) 148 :1418–1426 8. Tarp B, Jensen JS, Ostergaard L, Andersen PL: Search for agents causing atypical pneumonia in HIV-positive patients by inhibitor-controlled PCR assays. European Respiratory Journal (1999) 13 :175–179 9. Martin JN, Rose DA, Hadley WK, Perdreau-Remington F, Lam PK, Gerberding JL: Emergence of trimethoprim-sulphamethoxazole resistance in the AIDS era. Journal of Infectious Diseases (1999) 180 :1809–1818