Paolo Cadrobbi

Chronic hepatitis B in children after e antigen seroclearance: Final report of a 29‐year longitudinal study

Chronic hepatitis B is usually a benign disease in Caucasian children; however, the long‐term prognosis remains unsettled. This report describes the results of a 29‐year longitudinal study including 99 white children with chronic hepatitis B, mainly acquired horizontally: 91 were hepatitis B e antigen (HBeAg) positive (4 had cirrhosis), and 8 were HBeAg negative at presentation. Of the 91 HBeAg‐positive children, 89 underwent HBeAg seroconversion after a mean period of 5.2 ± 4.0 years and were included in the study. Of the 85 children without cirrhosis, one had HBeAg‐negative hepatitis and the other 84 became inactive carriers. During a mean follow‐up of 14.5 ± 6.1 years after HBeAg seroclearance, 4 carriers experienced reactivation, and 3 of them had HBeAg‐negative hepatitis at the last follow‐up. Of the 8 initially HBeAg‐negative children, 2 had HBeAg‐negative hepatitis, and 6 were inactive carriers. Of the 4 children with cirrhosis, 2 had hepatocellular carcinoma (HCC) and remained alive and 2 lost the histological features of cirrhosis in adulthood. Two patients with HBeAg‐negative hepatitis and 1 with cirrhosis had experienced drug abuse. At the end of follow‐up, 15 of the 89 initially HBeAg‐positive patients and 2 of 8 initially HBeAg‐negative children had cleared hepatitis B surface antigen. In conclusion, the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable; however, some patients progress to HCC and HBeAg‐negative hepatitis. Long‐term monitoring is important, as is counseling on cofactors of liver damage, such as alcohol and drug abuse. (HEPATOLOGY 2006;43:556–562.)

Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period

BACKGROUND/AIMSnChronic hepatitis B virus infection can lead to cirrhosis and hepatocellular carcinoma, particularly in men over 40 years of age and in areas where childhood-onset infection is common. The sequence of events from paediatric infection to severe disease in adults is only partially known. The aim of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood during 20 years of follow-up.nnnPATIENTSnOne hundred and eighty-five consecutive, otherwise healthy, Caucasian children were enrolled in Padua (Italy) and in Madrid (Spain) between 1975 and 1985, and followed for an average period of 13 years; 168 were hepatitis B e antigen (HBeAg) positive and five had cirrhosis.nnnRESULTSnThirty patients received steroids or levamisole and 21 interferon, but treatment did not significantly influence HBeAg clearance. Overall, two (1.1%) children, with initial cirrhosis, developed hepatocellular carcinoma and the other three (1.6%) cirrhotic patients became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; 14 (7.5%) children maintained HBeAg positive hepatitis; 155 (83.8%) became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; six (3.2%) experienced reactivation of liver disease and viral replication after remission and five (2.7%) maintained biochemical features of liver damage after HBeAg clearance. Only 6% cleared hepatitis B surface antigen.nnnCONCLUSIONSnEven considering the bias of treatment, the large majority of Caucasian children with chronic hepatitis B became asymptomatic carriers of infection with normal alanine amino-transferase during the first 20 years of observation. Cirrhosis is an early, rare complication, and a risk factor for hepatocellular carcinoma. A subgroup of patients who experienced reactivation or maintained liver damage after HBeAg clearance seems to be at greater risk for disease progression during adult life.

Severe Hepatic Failure Related to Nevirapine Treatment

markable. Laboratory evaluations were significant for a leukocyte count of 1,500/mm (normal value, 4,500–11,000/mm) and macrocytic anemia (hematocrit, 30%; hemoglobin level, 9.8 g/dL; mean corpuscular volume, 104.6 fL). The absolute neutrophil and lymphocyte counts were 870 and 600/mm, respectively. The blood urea nitrogen level was 34 mg/dL (normal value, 7–22 mg/dL), and the creatinine level was 1.8 mg/dL (normal value, 0.6–1.3 mg/dL). Blood cultures were negative. Direct fluorescent antibody staining of fluid from one of the vesicles was positive for HSV, and viral cultures subsequently yielded HSV. A punch biopsy of one of the lesions revealed epidermal ulceration with florid viral cytopathic changes consistent with herpesvirus infection. Secondary bacterial colonization was noted. The patient was treated with intravenous acyclovir (5 mg/kg three times a day), and there was subsequent resolution of the lesions with scarring. Ecthyma refers to a cutaneous infection resembling impetigo but affecting areas deeper in the skin. The lesions are characterized by localized, well-demarcated, erythematous plaques with ulceration that reaches the dermis. Therefore, the lesions often have a central eschar and cause scarring [1]. Ecthyma is almost always secondary to streptococcal and staphylococcal infections, in particular Streptococcus pyogenes infection; therefore, treatment for ecthyma generally consists of oral antimicrobials that are active against S. pyogenes and Staphylococcus aureus. However, mucormycosis [2, 3], molluscum contagiosum [4], cutaneous diphtheria [5], and gonococcal infections [6] have all been associated with ecthyma-like cutaneous eruptions. Review of the literature with use of MEDLINE revealed no previously reported cases of an ecthyma-like presentation of HSV infection. On the basis of nomenclature, ecthyma should be distinguished from two similarly named conditions, ecthyma gangrenosum and contagious ecthyma. Ecthyma gangrenosum is a life-threatening condition secondary to bacterial septicemia with gram-negative bacteria, in particular Pseudomonas aeruginosa. It is characterized by well-demarcated, indurated, weeping, necrotic eschars in areas rich in apocrine glands. Contagious ecthyma, also known as orf, is a parapoxvirus infection of the skin acquired from sheep that is characterized by ulcerated erythematous nodules with white halos. A history of contact with sheep is almost invariably present. This case presents a novel manifestation of HSV infection in immunocompromised hosts. Other such manifestations include painful ulcerative lesions of the genitalia, perianal area, and lips and follicular facial lesions [7]. Moreover, HSV infections should be considered in the differential diagnosis of ecthyma-like skin lesions in immunocompromised patients, and biopsies and virological studies should be performed to exclude HSV infections.

Antibodies to hepatitis C virus in community-acquired acute non-A, non-B hepatitis

Circulating antibodies to the recently identified hepatitis C virus (anti-HCV) have been investigated by ELISA in a series of 129 adult Italian patients with acute, community-acquired non-A, non-B hepatitis. Anti-HCV was detected in 50 (38%) cases with a prevalence rate which increased from 19%, in sera taken during the first 2 weeks of illness to 52% in samples obtained 5-6 weeks after onset, indicating a rather late appearance of the antibody. Anti-HCV positivity was independent of risk factors in the clinical history, but correlated with the outcome of the disease. Eighteen (26%) of 68 patients who recovered were anti-HCV positive compared to 10 of 14 (71%) who progressed to chronicity (p less than 0.01). In this latter group the antibody persisted for more than 12 months after the onset of the illness. Conversely, in 12 (85%) of 14 serially tested patients who recovered, anti-HCV positivity was transient, lasting from a few weeks to a few months. These findings indicate that HCV is implicated in a consistent proportion of acute community-acquired non-A, non-B hepatitis cases, particularly cases which progress to chronicity. A large proportion of cases remained unclassified, however, and it will be important to define whether they represent cases of HCV infection with poor serologic response, or are due instead to other, as yet unidentified, non-A, non-B agents.

Changes in hepatitis Be antigen/antibody system in children with chronic hepatitis B virus infection

The long-term changes in the HBeAg/anti-HBe system were examined in 55 children with chronic type B hepatitis (52 patients) or cirrhosis (three patients) during a follow-up period of two to 10 years. At the time of presentation, positive reactions to HBeAg were seen in 46 children, and to anti-HBe in nine. Spontaneous seroconversion from HBeAg to anti-HBe occurred in 13 of 38 patients (average annual rate 16%), mainly those with acute onset of hepatitis B or with features of active liver disease at presentation and with a focal distribution pattern of hepatitis B core antigen in the liver. Normalization of transaminase activity and disappearance of histologic features of activity were the rule in patients in whom seroconversion occurred, but the exception in those who maintained persistently HBeAg-positivity. In contrast to the favorable evolution of illness observed in children showing anti-HBe seroconversion, three of nine patients who had anti-HBe-positive reactions at presentation were found to have liver cirrhosis, and a fourth patient had features of active hepatitis throughout the observation period. Because delta antigen was detected in the liver in two of these patients, it is conceivable that etiologic cofactors could have influenced their course of chronic hepatitis.

Synercid plus vancomycin for the Treatment of Severe Methicillin-resistant Staphylococcus aureus and Coagulase-negative Staphylococci Infections: Evaluation of 5 Cases

Synercid (quinupristin/dalfopristin), the first semi-synthetic injectable streptogramin, is a promising alternative to glycopeptides against many Gram-positive multiresistant bacteria. Vancomycin is still considered an effective agent for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections but therapeutic failures with glycopeptides have been observed, even for the treatment of infections caused by S. aureus strains sensitive to vancomycin. Synercid, in combination with a glycopeptide, may address this problem without causing significant side effects due to the different toxicity patterns of the 2 antimicrobials. This study reports our experience with the combination of Synercid and vancomycin in 5 patients with severe infection caused by MRSA or methicillin-resistant coagulase-negative Staphylococcus.

Leuconostoc Species: A Case-cluster Hospital Infection

Leuconostoc species are members of the Streptococcacae family. They are generally regarded as non-pathogenic culture contaminants and are thought to be an uncommon cause of infection. We present a study of a case-cluster nosocomial infection due to Leuconostoc spp. Three patients were hospitalized at the time of the infection with significant underlying diseases and all had a compromised skin and mucous barriers. Two had received previous antibiotic therapy. This report highlights the importance of Leuconostoc spp. as an emerging pathogen, even though the modes of transmission and reservoirs of Leuconostoc spp. are as yet unknown.

Epidemiological aspects of acute viral hepatitis in drug abusers

SummaryThe epidemiological features of acute symptomatic viral hepatitis were examined in 151 consecutive, hospitalized drug abusers. Hepatitis B was diagnosed in 101 patients (66.8%), hepatitis A in 13 (8.6%) and non-A, non-B hepatitis in 35 (23.1%). Non-A, non-B hepatitis was significantly more prevalent among drug abusers than in an age-matched control population of non-drug abusers. Moreover, the mean duration of parenteral drug abuse was significantly lower among non-A, non-B cases than in patients with hepatitis A or B. These results suggest a wide circulation of both hepatitis B virus and non-A, non-B agent(s) among drug abusers in our area. These patients most likely represent a main reservoir of non-A, non-B infection due to the high rate of chronicity reported for non-A, non-B hepatitis.ZusammenfassungEpidemiologische Charakteristika der akuten Virus-Hepatitis wurden an 151 fortlaufend erfaßten Drogensüchtigen untersucht, die stationär behandelt wurden. Bei 101 Patienten (66,8%) wurde eine Hepatitis B, bei 13 (8,6%) eine Hepatitis A und bei 35 (23,1%) eine Nicht-A, Nicht-B Hepatitis diagnostiziert. Bei Drogensüchtigen war die Nicht-A, Nicht-B Hepatitis signifikant häufiger als bei einer altersentsprechenden nicht drogenabhängigen Kontrollgruppe. Den Fällen von Nicht-A, Nicht-B Hepatitis ging im Mittel eine kürzere Phase von parenteralem Drogenmißbrauch voraus als den Erkrankungen an Hepatitis A oder Hepatitis B. Daraus läßt sich schließen, daß das Hepatitis B Virus und das Hepatitis Nicht-A, Nicht-B Virus bei den Drogenabhängigen in unserem Kreis in beträchtlichem Ausmaß zirkulieren. Es ist wahrscheinlich, daß diese Patienten infolge der für Nicht-A, Nicht-B Hepatitis mitgeteilten hohen Rate an chronischen Verläufen ein Hauptreservoir für die Nicht-A, Nicht-B Hepatitis darstellen.

Different mechanisms responsible for in vitro cell-mediated cytotoxicity to autologous hepatocytes in children with autoimmune and HbsAg-positive chronic liver disease

To investigate mechanisms of hepatocyte injury, lymphocytes from 41 children with chronic liver disease were incubated with autologous liver cells in a microcytotoxicity assay. Cytotoxicity was significantly increased in 18 of 25 patients with chronic hepatitis B virus (HBV) infection, in five of nine with autoimmune chronic active hepatitis (CAH), and in only one of seven with histologically inactive liver disorders. There was a good correlation between cytotoxicity and biochemical and histologic markers of disease activity in children with autoimmune CAH, whereas in HBsAg-positive disease a positive correlation was found only with serum alanine aminotransferase (SGPT). Children with autoimmune CAH receiving steroid treatment had normal cytotoxicity, whereas increased values were found in two of three HBsAg-positive patients receiving prednisolone. Fractionation studies revealed that non-T cells were cytotoxic in both autoimmune and HBcAg-positive chronic liver disease. T cell cytotoxicity was exclusively found in children with chronic HBV infection, particularly with HBc antigenemia. Blocking experiments showed that T-lymphocytes from HBsAg-positive children reacted with HBV core antigen on the hepatocyte surface. Non-T cells were directed against hepatocyte membrane antigens in both HBsAg-positive and HbsAg-negative children. These results suggest that different immune mechanisms of liver damage are involved in autoimmune and HBsAg-positive chronic liver disease.

CHEMO-IMMUNOTHERAPY OF ADVANCED AIDS-RELATED KAPOSI'S SARCOMA

Aims and background Kaposis sarcoma (KS) is the most common neoplastic complication of HIV infection and AIDS. Multiple cytotoxic chemotherapy regimens have been used with various response rates. We have evaluated the efficacy and toxicity of low-dose chemotherapy in patients with poor-prognosis AIDS-related KS and the role of interferon alpha (IFN-α) in complete responders. Methods Twenty-five previously untreated patients with advanced KS received bleomycin (BL) 10 mg/m2 and vinblastine (VB) 6 mg/m2 on days 1 and 15 every two weeks. After six cycles, patients in complete remission received IFN-alpha (3 million U s.c. 3 times/week) combined with antiretroviral therapy. All patients were evaluated for toxicity using the World Health Organization (WHO) toxicity schedule. Both Eastern Cooperative Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria were used to evaluate response and survival. Results The overall response rate was 84% (95% confidence interval, 51–117%) with six complete remissions (24%) and 15 partial remissions (60%) by ECOG criteria, and 92% (95% confidence interval: 58–128%) with 17 partial remissions (68%) by ACTG criteria. The median duration of response on IFN-alpha treatment was 4.5 months (range, 2–10). The overall median survival duration for all 25 patients was 9 months (range, 2–39). Grade 3–4 anemia was observed in five patients and grade 3–4 neutropenia in two patients. No other clinically significant (> grade 3) toxicities were observed. Conclusions Combination of BL and VB is effective and well tolerated, even if new therapeutic options are developing. This disease remains a challenging problem, so larger studies using the combination of chemotherapy and/or IFN-alpha with antiretroviral treatment are warranted.