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.

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.

Pleural effusion and pulmonary injury as an unusual complication to chemotherapy in non-small cell lung cancer patients.

We report the appearance of pleural effusion, or pulmonary failure after chemotherapy, followed by tumor reduction, in a small number of patients. Five hundred and fifty-four patients with lung cancer have undergone chemotherapy at our Institute during the last ten years. Three patients with non-small cell lung cancer (NSCLC), with locally advanced disease, exhibited an unusual consequence following cytotoxic drug treatment. Two patients with NSCLC had pleural effusion which improved within 2-3 weeks, together with tumor reduction, which allowed the continuation of treatment. One patient had pulmonary failure with pleural effusion and recovered within two weeks. Two of the three patients had positive cytology for cancer cells in the fluid. All three patients achieved partial remission with no repetition of the complication. The patients' recovery, response to treatment and the tumor reduction suggest that this complication was not due to disease progression.

Splenic infarct as a late complication of liver transplantation.

Splenic infarct is a rare complication of portal hypertension. It has been reported as an early complication after successful liver transplantation when portal pressure returns to normal and the splenic size progressively declines. It has not been reported as a late complication of liver transplantation. We describe the case of a 19-year-old patient with a splenic infarct which occurred 11 months after successful orthotopic liver transplantation for decompensated cryptogenic liver cirrhosis. Following transplantation, the patient was in excellent general health, liver function tests were normal, there was no clinical evidence of portal hypertension and the splenic size had decreased significantly compared to the pre-transplantation period, although it remained increased. The patient presented with high fever, left pleuritic pain and vomiting. The splenic size had not changed and left pleuritic exudate fluid collection was detected. A hypoechoic region of the spleen was demonstrated in the ultrasound examination corresponding to a hypodense lesion in the computerized tomography scanning. The patient recovered completely, with the disappearance of the infarct in the imaging studies in 2 months time. This case report indicates that a symptomatic splenic infarct can occur late following successful liver transplantation for liver cirrhosis despite lack of any evidence of residual portal hypertension at a time that splenomegaly has not yet regressed. The differential diagnosis from a splenic abscess in transplanted patients can be difficult but the final prognosis seems to be good.

A case of haemosuccus pancreaticus.

Haemosuccus pancreaticus (Wirsungorrhagia or pseudohaemobilia) is a rare complication of chronic pancreatitis. We describe a 48-year-old patient with alcohol-induced chronic calcific pancreatitis and recurrent episodes of severe upper gastrointestinal bleeding but without abdominal pain. Upper gastrointestinal endoscopy revealed fresh blood oozing from the ampulla of Vater. No pseudoaneurysms or pseudocysts were detected by arteriography or computerized tomography. The bleeding was attributed to pancreatic lithiasis. Following conservative treatment, there was no evidence of recurrence during a 24-month follow-up period. In conclusion, although a rare occurrence, haemosuccus pancreaticus should be considered in the differential diagnosis of all cases of obscure upper gastrointestinal bleeding in patients with chronic pancreatitis, whether or not accompanied by pain. A highly suggestive clinical history or X-ray findings and an endoscopic visualization of blood coming from the ampulla of Vater may suffice for the diagnosis, thus avoiding diagnostic and therapeutic errors. When haemosuccus pancreaticus occurs in patients without pseudoaneurysms or pseudocysts, it can be treated conservatively, thus obviating the need for pancreatectomy or arteriographic embolization.

Gliclazide-induced acute hepatitis.

There are few reports in the literature related to sulfonylurea-induced hepatotoxicity. We describe the case of acute hepatitis induced by gliclazide, a second generation sulfonylurea. A 60-year-old woman with diabetes mellitus (type 2) developed an acute icteric hepatitis-like illness 6 weeks after the initiation of gliclazide therapy. Other causes of acute hepatocellular necrosis were excluded. Liver histology showed marked portal inflammation with lymphocytes, monocytes and eosinophils, associated with lobular inflammation (indicative of a histological pattern consistent with drug-induced hepatitis). The drug was immediately withdrawn and the patient was given glibenclamide. The patient recovered clinically and, in less than 4 weeks, her serum bilirubin and aminotransferases returned to normal levels. We believe that this is the first description of acute hepatitis caused by an idiosyncratic adverse reaction to gliclazide or to one of its metabolites. In conclusion, this case strongly suggests that gliclazide can induce acute icteric liver necro-inflammation which may be misdiagnosed clinically as acute viral hepatitis. In patients who show abnormal liver function tests, the immediate discontinuation of gliclazide is recommended.

Fulminant hepatic failure as a presenting paraneoplastic manifestation of Hodgkin's disease.

Malignancies may uncommonly present as fulminant hepatic failure and, due to the rarity of such an occurrence, they may easily be overlooked as one of its possible causes. An unusual case of Hodgkin's disease presenting as a fulminant hepatic failure is reported. A 34-year-old man presented with an acute onset of liver failure characterized by jaundice, ascites, encephalopathy and bleeding diathesis. Chemotherapy was initiated, resulting in a dramatic improvement not only in the patient's level of consciousness, but also in prothrombin time. Unfortunately, he succumbed shortly after to disseminated candidiasis. A post-mortem needle liver sample revealed massive hepatocellular necrosis, but no liver infiltration by the neoplastic disease. We conclude that in Hodgkin's disease, involvement of the liver can be manifested as a syndrome of paraneoplastic fulminant hepatic failure. In such cases, liver transplantation is an absolute contraindication but urgent chemotherapy under antifungal surveillance can be life saving.

Cholestatic jaundice as a paraneoplastic manifestation of renal cell carcinoma.

Malignant diseases may cause cholestatic jaundice through either main bile duct obstruction or widespread hepatic metastasis. Renal cell carcinoma (hypernephroma, RCC) can cause a variety of paraneoplastic manifestations which can be the main presenting symptoms. Cholestasis, as a paraneoplastic syndrome, has been well described in patients with malignant lymphohyperplastic diseases. Non-metastatic nephrogenic hepatic dysfunction syndrome without jaundice has often been described in patients with hypernephroma (Stauffer's syndrome). Paraneoplastic cholestatic jaundice has not yet been described. We report, for the first time, two patients who presented with pruritus and cholestatic jaundice. During the diagnostic work-up, RCC was diagnosed. The renal tumour was an unexpected finding during computed tomographic (CT) scan. No clinical manifestations of hypernephroma, short of microscopic haematuria, were detected. Conjugated bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase were markedly increased. No hepatic metastasis or main bile duct obstruction were detected by appropriate investigations. After radical nephrectomy, liver abnormalities disappeared rapidly. We conclude that RCC should be included among neoplasms causing not only anicteric intrahepatic cholestasis but also frank jaundice as part of a paraneoplastic syndrome. The differential diagnosis from hepatic metastasis, main bile duct obstruction or other causes of jaundice is of clinical importance and of prognostic value. Patients with unexplained cholestasis should be investigated for malignant diseases including hypernephroma.

Autoimmune hepatitis associated with the antiphospholipid syndrome.

The antiphospholipid syndrome has rarely been described in patients with autoimmune hepatitis. Two cases with type I autoimmune hepatitis and antiphospholipid syndrome are presented. The first case is that of a 53-year-old Caucasian female with a history of arterial thrombosis and fetal loss who was submitted to clinical and laboratory testing due to persistent transaminasaemia and was found to have autoimmune hepatitis. Antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) were positive. The second case is that of a 31-year-old Caucasian woman with a history of autoimmune hepatitis who was submitted to laboratory testing due to a second-trimester fetal death, revealing an increased activated partial thromboplastin time and positive antiphospholipid antibodies. In conclusion, secondary antiphospholipid syndrome may accompany autoimmune hepatitis.

Polymyositis associated with primary biliary cirrhosis.

The coexistence of polymyositis (PM) and primary biliary cirrhosis (PBC) is rare; only nine cases have been described in English literature. We report a case of a 46-year-old woman presenting with these two autoimmune diseases. The diagnosis of PM was based on the symmetrical, proximal limb muscle weakness, elevated muscle enzymes and was confirmed with the electromyography and muscle biopsy. The diagnosis of PBC was based on the increased serum levels of alkaline phosphatase, gamma glutamyltransferase, IgM immunoglobulin, the presence of antimitochondrial antibodies and diagnostic liver biopsy.

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.

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.

Prolonged cholestatic jaundice after endoscopic retrograde cholangiography.

The main complications of endoscopic retrograde cholangiography and sphincterotomy are bleeding, pancreatitis, perforation and sepsis. Two cases of unexplained prolonged cholestatic jaundice in patients who underwent endoscopic retrograde cholangiography (ERC) for biliary obstruction due to choledocholithiasis are reported. The patients were admitted because of right upper quadrant pain, vomiting and jaundice. Laboratory tests showed increased levels of total and conjugated serum bilirubin and increased alkaline phosphatase. Ultrasound examination showed cholelithiasis and choledocholithiasis with bile duct dilatation. ERC with sphincterotomy was performed and gallstones obstructing the common bile duct were removed endoscopically. Following ERC and despite complete patency of the biliary tree, a progressive increase of total and conjugated bilirubin and of alkaline phosphatase was noted, associated with itching and total stool discoloration. The insertion of nasobiliary drain did not improve the jaundice. Prednisolone treatment for 12 days was associated with progressive restoration of serum bilirubin alkaline phosphatase to normal levels. It was postulated that the radiocontrast material used may have acted toxically on the liver with disruption of the canalicular plasma membrane. It is proposed that intrahepatic cholestasis should be added in the list of complications of endoscopic retrograde cholangiography.