Intestinal colonization with resistant bacteria: a prognostic marker of mortality in decompensated cirrhosis.

Infections due to drug-resistant (DR) bacteria are increasingly recognized as an emerging problem worldwide. Asymptomatically colonized patients may contribute to the reservoir in the hospital setting, causing both horizontal transmission and endogenous infections. We aimed to evaluate the prevalence of intestinal colonization with DR bacteria on subsequent clinical infection development and prognosis in patients with decompensated cirrhosis. One hundred seven patients without infection at baseline were screened and prospectively followed-up for 3 months. Among the patients screened, DR bacteria were isolated in 47 (43.9%), 14 colonized with multidrug- (MDR) and 33 with extensively drug (XDR)-resistant bacteria or a mixture of MDR/XDR bacteria. Severity of liver disease and demographic characteristics were similar among groups. The 20 (42.6%) with DR vs 14 (23.3%) without had hepatic encephalopathy and/or spontaneous bacterial peritonitis episodes over the past 6 months (p = 0.034). One third of both DR and non-DR groups developed infection during follow-up but in only 7 and 5, respectively, the infection was microbiologically documented. In a 3-month-follow-up period, mortality was higher in patients colonized with XDR compared to those without (log rank p = 0.027). In multivariate analysis, colonization with XDR bacteria [HR = 1.074, (CI:1.024-1.126), p = 0.003] and MELD score [HR = 2.579 (1.109-5.996), p = 0.028] were independently associated with low survival. Asymptomatic GI colonization with DR bacteria is a risk factor for increased mortality in decompensated cirrhosis. Frequent hospitalizations for complications of the underlying disease and selective pressure induced by the use of antimicrobials are probably the main determinants.

Hepatitis B virus reactivation in patients receiving chemotherapy for malignancies: role of precore stop-codon and basic core promoter mutations.

Hepatitis B virus (HBV) strains carrying the precore stop-codon mutation (A1896) have been considered among the predisposing factors for reactivation during chemotherapy for malignancies. The role of the T1762/A1764 basic core promoter (BCP) mutations has not been fully evaluated. We aimed to record any changes in HBV serological markers after reactivation, detect the presence of A1896 and BCP mutations and evaluate the type of cytotoxic drugs involved. We retrospectively screened eight patients presenting with HBV reactivation following chemotherapy for malignancies. The chemotherapy regimens used included corticosteroids (CSs), fludarabine and cyclophosphamide/adriamycine. The INNO-LiPA HBV PreCore kit was used for the detection of the A1896 and BCP mutations. Six patients who were hepatitis B surface antigen (HBsAg)-(+)/hepatitis B e antigen (HBeAg)-(-) before chemotherapy, had disease reactivation following a mean of four cycles of chemotherapy. Four survived and two died of hepatic failure. At the time of reactivation, all six patients carried the A1896 and five of them the BCP mutations. The remaining two patients were HBsAg-(-)/anti-HBs-(+)/anti-hepatitis B core (HBc)-(+)/HBeAg-(-) before chemotherapy. One of them reverted to HBeAg-(+) status but remained HBsAg-(-), while the other became HBsAg-(+)/HBeAg-(+), following three and eight cycles of fludarabine treatment, respectively. The former carried the A1896 and the latter the wild-type virus. Both died from causes associated with their haematological disease. All but one of our patients with HBV reactivation during chemotherapy carried the precore stop-codon and BCP mutations. Whether this occurs more frequently in such patients than those carrying the wild-type virus needs further investigation. Fludarabine should be added to the list of drugs inducing HBV reactivation. HBV reactivation following fludarabine treatment occurred in HBsAg-(-) patients who had been anti-HBs-(+).

Genetic heterogeneity of hepatitis viruses and its clinical significance.

The genetic heterogeneity of hepatitis B virus (HBV) (8 genotypes A-H) has been applied for tracing the route of HBV transmission and the geographical migration of HBV carriers but it also appeared to have clinical implications. The secondary structure of e encapsidation signal could explain why the precore mutant virus prevails in Mediterranean countries, where genotype D is most prevalent, while the wild type virus is frequent in Western countries, where genotype A is most prevalent. There is increasing evidence that patients infected with genotype C have more severe outcome of chronic liver disease than those infected with genotype B. Genotype B was associated with fulminant hepatitis and more severe episodes of acute exacerbation of chronic HBV infection. Patients infected with genotype B appeared to seroconvert earlier than those infected with genotype C. The hepatitis delta virus (HDV) has 3 genotypes (I, II, III) which are associated with different disease patterns. Genotype III is the most distantly related HDV genotype and is associated with the most severe outcome while genotype II with relatively mild liver disease. The most geographically widespread genotype is I and is associated with a broad spectrum of chronic liver disease. The hepatitis C virus (HCV) displays high genetic heterogeneity with six genotypes (1-6), multiple subtypes and quasispecies. This viral diversity has epidemiological and clinical implications and has been associated with the severity of liver disease, prognosis, response to treatment and failure to generate an effective protective vaccine. HCV genotype 1 is the predominant genotype in Western countries and has been associated with a low response rate to interferon-alpha (IFN-alpha) or to the combination of ribavirin and IFN-alpha. Consequently the duration of treatment has been tailored according to HCV genotype.

Immune thrombocytopenic purpura in a patient treated with interferon alfacon-1.

Immune thrombocytopenic purpura is an acquired disorder characterized by severe thrombocytopenia and caused by one or more antiplatelet autoantibodies. We present a case of a 20-year-old woman referred to our Unit for chronic hepatitis C virus (HCV) infection. At week 28 of treatment with interferon (alfacon-1), undetectable HCV RNA and transaminase levels within normal limits, the patient presented with immune thrombocytopenic purpura, which was successfully treated with immunoglobulin and methylprednisolone. Despite the high doses and long life of corticosteroid treatment HCV RNA remained undetectable.

The autoimmune lymphoproliferative syndrome (Canale-Smith) in adulthood.

The autoimmune lymphoproliferative syndrome (ALPS) or Canale-Smith syndrome is a recently described clinical entity consisting of chronic, non-malignant lymphadenopathy and hepatosplenomegaly together with hypergammaglobulinemia, positive autoantibodies and/or overt autoimmune diseases. It is caused by a genetic defect in the mechanism of programmed cell death (apoptosis) and is characterized by the presence of double-negative (TCR alpha/beta CD4- CD8-) T lymphocytes (DNT). Although well known in pediatric patients, ALPS is an unusual diagnosis in adults. The oldest reported patient was aged 54. We describe another two adult patients in whom a presenting autoimmune disease led to the diagnosis of ALPS.

Intestinal pseudo-obstruction and ureterohydronephrosis as the presenting manifestations of relapse in a lupus patient.

Intestinal pseudo-obstruction (IPO) is a rare complication of systemic lupus erythematosus (SLE). We present a 32-year old female with SLE for seven years. She was admitted with profound fatigue, frequent vomiting, colicky abdominal pain, diarrhoea and intermittent dysuria for the past 12 months. Imaging studies revealed dilated small and large bowel loops with thickened intestinal wall and multiple fluid levels. Urinary tract involvement was also demonstrated. The patient responded well to immunosuppressive treatment. IPO in the context of SLE has been described only in anecdotal case reports. Half of the cases developed this complication during the course of lupus as in the present case. Concomitant ureterohydronephrosis was present in approximately two-thirds of the cases. Early recognition of the syndrome is necessary for the institution of the appropriate medical treatment and prevention of inappropriate surgical intervention.

Pituitary non-secreting macroadenoma apoplexy in an adolescent. patient report and review of the literature.

Pituitary macroadenomas are rare in children and adolescents, and when encountered are usually hormone secreting. Symptomatic pituitary non-secreting macroadenoma apoplexy in an adolescent is rare and potentially life-threatening. A 15 year-old patient is described, hospitalized due to headache, fever and photophobia 4 days prior to admission. A meningeal syndrome was postulated, based on clinical examination and cerebrospinal fluid testing. However, clinical examination and hormone testing revealed partial failure of the anterior pituitary. Computed tomography of the brain demonstrated a space-occupying lesion of the pituitary. Magnetic nuclear resonance imaging suggested the presence of a pituitary macroadenoma. Hypophysectomy was performed. Histological examination revealed an extensive infarction of a pituitary adenoma. Hormonal substitution with thyroxine and corticosteroids was administered. This report emphasizes that pituitary non-secreting macroadenoma apoplexy may rarely be the cause of headache and fever in an adolescent, thus causing difficulties in differential diagnosis from acute meningitis.