Luciano Attard

Non—Organ-Specific Autoantibodies in Children with Chronic Hepatitis C: Clinical Significance and Impact on Interferon Treatment

We evaluated the prevalence and clinical significance of non-organ-specific autoantibodies (NOSAs) in 47 hepatitis C virus (HCV)-positive children with abnormal alanine transaminase levels and analyzed the association between NOSAs and virus level, genotype, human leukocyte antigen status, and interferon (IFN) response. Forty-two hepatitis B virus (HBV)-positive children and 25 age- and sex-matched healthy children served as control subjects. NOSAs were found in 34% of the HCV-positive children, 12% of the HBV-positive controls, and none of the healthy control subjects. Liver-kidney microsomal antibody type 1 (LKM1) was detected in 11% of the HCV-positive children but in none of the controls. The HCV load was significantly higher in NOSA-negative than in NOSA-positive children. HCV genotype distribution and human leukocyte antigen alleles were similar, irrespective of NOSA status. Long-term response to IFN therapy was achieved by 18% of the NOSA-positive and 55% of the NOSA-negative subjects. Two LKM1-positive children developed acute, self-limited hepatocellular necrosis while receiving IFN therapy. NOSAs are frequently present in children with hepatitis C, who are less likely to benefit from IFN therapy.

Familial hemophagocytic lymphohistiocytosis may present during adulthood: clinical and genetic features of a small series.

Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare immune deficiency with defective cytotoxic function. The age at onset is usually young and the natural course is rapidly fatal if untreated. A later onset of the disease has been sporadically reported even in adolescents and adults. We report the results of our retrospective data collection of all cases diagnosed with FHL at an age of 18 years or older and enrolled in the Italian Registry of HLH. All cases were diagnosed with FHL based on evidence of genetic defect in one FHL-related gene. A total of 11 patients were diagnosed with FHL. They were 9 males and 2 females, from 10 unrelated families; their age ranged between 18 and 43 years (median, 23 years). Family history was unremarkable in eight families at the time of the diagnosis. Their genetic diagnoses are: FHL2 (n = 6), FHL3 (n = 2), FHL5 (n = 1), XLP1 (n = 2). Clinical, molecular and functional data are described. These data confirm that FHL may present beyond the pediatric age and up to the fifth decade. FHL2 due to perforin defect is the most frequently reported subtype. Adult specialists should consider FHL in the differential diagnosis of patients with cytopenia and liver or central nervous system disorders, especially when a lymphoproliferative disease is suspected but eventually not confirmed. FHL may turn to be fatal within a short time course even in adults. This risk, together with the continuous improvement in the transplant technique, especially in the area of transplant from matched unrelated donor, resulting in reduced treatment related mortality, might suggest a wider use of SCT in this population. Current diagnostic approach allows prompt identification of patients by flow-cytometry screening, then confirmed by the genetic study, and treatment with chemo-immunotherapy followed by stem cell transplantation.

HLA DR13 and HCV vertical infection.

Risk factors affecting vertical hepatitis C virus (HCV) transmission are not completely known, if we exclude maternal HIV coinfection. We hypothesized that immunogenetic factors related to maternal or neonatal HLA profiles may affect HCV vertical transmission. HLA typing (microcytotoxicity assay on blood samples) was performed in 18 infants affected by vertically transmitted HCV infection and in 17 serum-reverted infants. (Serum-reversion is defined as antibody negative by 1 year of age and persistently HCV-RNA negative.) Moreover, HLA typing was performed in 20 mothers. Logistic regression analysis showed a significant negative association between childrens HLA-DR13 antigens and risk of HCV vertical transmission (p < 0.01). This association persisted in a model including the maternal HIV status: HLA DR13 and maternal HIV coinfection showed a separate, opposite effect on vertical HCV infection (p < 0.01 and p < 0.001, respectively). The relative risk estimate for the ratio of not-infected to infected children in the presence of DR13 was 8.4 (95% confidence bounds, 1.1–60.8). Breast-feeding did not affect the risk of vertical HCV transmission. Maternal HLA profile did not relate to vertical infection. The present study reveals a significant association between HLA-DR13 and the likelihood of seroreversion in infants born to HCV-infected mothers. The findings of the present study could help in better understanding the pathogenesis of vertical HCV infection and in better identifying the cases at higher risk, which would be useful for the development of prevention strategies. It is possible that DR13 modulates the immune response to viruses, enhancing their clearance and, thus, in the case of HCV, exerting a protective role against the development of vertical infection.

Acute hepatitis induced by traditional chinese herbs used in the treatment of psoriasis

To the Editor , Herbal remedies are increasingly being employed in developed countries for the treatment of several disorders, such as gastrointestinal, hepatic, renal, and skin diseases. However, several reports have implicated traditional herbs in different types of liver damage, including abnormal liver tests, acute hepatitis, steatosis, chronic hepatitis, hepatic fibrosis, bile-duct injury, venoocclusive disease, and massive hepatic necrosis with acute liver failure. Particularly, several cases of Chinese herbal medicine-induced liver disease have been reported to date in the literature. 1,2

Ongoing outbreak of visceral leishmaniasis in Bologna Province, Italy, November 2012 to May 2013.

An increased number of autochthonous visceral leishmaniasis (VL) cases has recently been reported in Bologna Province in northern Italy. Over six months from November 2012 to May 2013, 14 cases occurred, whereas the average number of cases per year was 2.6 (range: 0-8) in 2008 to 2012. VL was diagnosed in a median of 40 days (range: 15-120) from disease onset. This delay in diagnosis shows the need for heightened awareness of clinicians for autochthonous VL in Europe.

A randomized trial of induction doses of interferon alone or in combination with ribavirin or ribavirin plus amantadine for treatment of nonresponder patients with chronic hepatitis C

BackgroundEfficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment.MethodsThe study was designed to have 225 HCV nonresponder patients, but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been randomized to receive interferon-α2a (group A, n = 26), interferon-α2a plus 15 mg/kg per day of ribavirin (group B, n = 24), or interferon-α2a plus ribavirin plus 200 mg/day of amantadine hydrochloride (group C, n = 25). Treatment duration was 48 weeks. The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks.ResultsOn intention-to-treat, the sustained virological response at 24 weeks of follow-up was 11.5% in group A, 12.5% in group B, and 12% in group C. Therapy was discontinued because of adverse effects in three patients in group A (11.5%), three in group B (12.5%), and two in group C (8%).ConclusionsNonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12% if retreated with interferon induction treatment followed by administration of a daily dose. The addition of ribavirin or amantadine did not seem to improve the response rates.

Schistosoma mansoni Eggs in Spleen and Lungs, Mimicking Other Diseases

1 Center for Tropical Diseases, Ospedale Sacro-Cuore Don Calabria, Negrar, Verona, Italy, 2 Infectious Diseases Unit, Department of Medical and Surgical Sciences, Ospedale S. Orsola-Malpighi, Alma Mater Studiorum University of Bologna, Bologna, Italy, 3 Acute and Chronic Viral Hepatitis Department, Seconda Universita degli Studi di Napoli, Naples, Italy, 4 Department of Pathology, Ospedale Sacro-Cuore Don Calabria, Negrar, Verona, Italy

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department

Background The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome

We describe a case of chronic fatigue syndrome (CFS) associated to Parvovirus B19 infection where administration of intravenous immunoglobulins (IVIG), previously reported as effective, induced a paradoxical clinical response and increased viral replication. The indication of IVIG administration in the treatment of Parvovirus B19-associated CFS should be carefully reconsidered.

Polyphasic type A hepatitis: histological features.

SummaryThe histology of polyphasic type A hepatitis was analyzed in liver biopsy specimens of two patients. The microscopic examination showed, together with changes of acute viral hepatitis, portal plasma cell infiltration, limiting plate erosion and porto-portal bridging necrosis. These features, although sometimes described in classical HAV hepatitis, appear to be similar to those commonly observed in severe and evolving forms of acute hepatitis due to other hepatotropic viruses. Only careful serological analyses can lead to a correct diagnosis and prognosis in case of polyphasic type A hepatitis.ZusammenfassungBei zwei Patienten mit polyphasischer Hepatitis A standen Leberbiopsien für die histopathologische Untersuchung zur Verfügung. Neben Veränderungen der akuten Virushepatitis fanden sich portale Plasmazellinfiltrationen, eine Erosion der Endplatte und Brückennekrosen. Diese Veränderungen werden manchmal auch bei der klassischen Hepatitis A beschrieben. Sie ähneln jedoch mehr den Veränderungen, die man bei schweren, fortschreitenden Formen von Infektionen durch andere hepatotrope Viren beobachtet. Nur die sorgfältige serologische Diagnostik kann zu einer korrekten Diagnose und prognostischen Beurteilung der polyphasischen Hepatitis A führen.The histology of polyphasic type A hepatitis was analyzed in liver biopsy specimens of two patients. The microscopic examination showed, together with changes of acute viral hepatitis, portal plasma cell infiltration, limiting plate erosion and porto-portal bridging necrosis. These features, although sometimes described in classical HAV hepatitis, appear to be similar to those commonly observed in severe and evolving forms of acute hepatitis due to other hepatotropic viruses. Only careful serological analyses can lead to a correct diagnosis and prognosis in case of polyphasic type A hepatitis. Bei zwei Patienten mit polyphasischer Hepatitis A standen Leberbiopsien für die histopathologische Untersuchung zur Verfügung. Neben Veränderungen der akuten Virushepatitis fanden sich portale Plasmazellinfiltrationen, eine Erosion der Endplatte und Brückennekrosen. Diese Veränderungen werden manchmal auch bei der klassischen Hepatitis A beschrieben. Sie ähneln jedoch mehr den Veränderungen, die man bei schweren, fortschreitenden Formen von Infektionen durch andere hepatotrope Viren beobachtet. Nur die sorgfältige serologische Diagnostik kann zu einer korrekten Diagnose und prognostischen Beurteilung der polyphasischen Hepatitis A führen.