Alexandra Alexopoulou

Adverse drug reactions as a cause of hospital admissions: a 6-month experience in a single center in Greece.

BACKGROUND Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. METHODS A prospective study was conducted over a 6-month period. All patients consecutively admitted were enrolled in the study. Analysis included: (1) an evaluation of the frequency of ADR-related hospital admissions and their causality, severity, and preventability; (2) a description of the type of drugs involved; (3) a report of the most common clinical manifestations related to these ADRs; and (4) an assessment of the factors that were predictive of ADRs. RESULTS Seventy of the 548 admissions (12.8%) were related to an ADR. Hemorrhage represented the most common ADR (37.3%), followed by metabolic and renal events (10.8% each). The drugs most often involved were non-steroid anti-inflammatory drugs (NSAIDs), followed by diuretics, aspirin, oral anticoagulants, and oral hypoglycemic agents. A comparison between ADR and non-ADR-related admissions showed that mean number of medications and age were significantly higher for patients admitted for an ADR than for those who were not. Gender, chronic disease at admission, days of hospitalization, cognitive impairment, renal insufficiency, physical activity impairment, and use of psychoactive drugs did not differ between the two groups. In the multivariate analysis, number of drugs was the only independent predictor of ADR-related hospital admission (OR=1.064, 95% CI 1.019-1.109). In 13 of 70 (18.6%) ADR-related hospital admissions, ADRs were coded as severe. CONCLUSIONS ADRs are common causes of hospital admissions and may have important consequences. The most important determinant for ADR-related hospital admissions is the number of drugs taken.

Pylephlebitis: an overview of non-cirrhotic cases and factors related to outcome.

Abstract Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971–1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis.

Increasing frequency of gram‐positive cocci and gram‐negative multidrug‐resistant bacteria in spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is historically caused by Gram‐negative bacteria (GNB) almost exclusively Enterobacteriaceae. Recently, an increasing rate of infections with Gram‐positive cocci (GPC) and multidrug‐resistant (MDR) microorganisms was demonstrated.

ACUTE LIVER FAILURE AS THE INITIAL MANIFESTATION OF HEPATIC INFILTRATION BY A SOLID TUMOR: REPORT OF 5 CASES AND REVIEW OF THE LITERATURE

Background Acute liver failure is a rare complication of metastatic liver disease with a high mortality. Recognition of malignant infiltration of the liver as the cause of acute liver failure could be a diagnostic challenge. Patients The medical files of 5 patients with acute liver failure due to metastatic liver disease collected over a 4-year period (1997–2000) in our department were reviewed. Results No patient had a past history of cancer. The interval from jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical examination revealed hepatomegaly and deep jaundice in all patients. AST elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from 74 to 556 IU/L (median, 138 IU/L). All patients died within 4–14 days (median, 7) of admission. None had papillary edema or decerebrate posture before death. Four patients had concurrent renal impairment. Liver imaging studies in 2 of the 5 patients were nondiagnostic and the malignant liver infiltration was confirmed postmortem. Liver histology in all cases showed massive tumoral infiltration of the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors were colon, gastric, small cell lung, pancreas and cancer of unknown origin. Conclusions Malignant infiltration of the liver should be taken into account in the differential diagnosis of rapidly progressive liver failure. Although effective chemotherapy has improved the survival of patients with metastatic liver disease, there has been no change in the course and outcome of acute liver failure due to malignant infiltration of the liver over the last 2 decades. A proper diagnosis by liver biopsy is mandatory to prevent such patients from being considered for liver transplant.

Hepatitis C virus infection in Greece and its role in chronic liver disease and hepatocellular carcinoma

The aim of this study was to evaluate the prevalence of hepatitis C virus infection (HCV) in Greece, to estimate its frequency in chronic liver disease and to explore the role of HCV infection in the aetiology of hepatocellular carcinoma. A series of 1034 patients with chronic liver disease of various aetioloigies and 299 patients with hepatocellular carcinoma allocated to two case-control studies was tested for anti-HCV. Twelve recent reports on HCV infection in Greece were reviewed and analyzed. The results of the present study indicate the existence of a large pool of HCV infection in Greece and an impressive spread of the virus in high-risk groups. Chronic HCV infection was found to account for 83.6% of patients with chronic non-A, non-B hepatitis parenterally transmitted, 56.5% of cases of sporadic community-acquired disease and for almost 1/4 of all patients with chronic liver disease. The relative risks for development of hepatocellular carcinoma of patients with chronic HCV infection was 6.3 in the first and 13.7 in the second case-control study, increasing to 20.0 and 18.7, respectively, when hepatitis B surface antigen (HBsAg) was positive. Serum HBV-DNA was positive and/or anti-HBc IgM levels were high in 12 of 15 (80%) patients with hepatocellular carcinoma positive only for HBsAg, and in 7 of 15 (47%) positive both for HBsAg and antibodies to HCV. The present data support the view that hepatitis B and C virus have an interacting role in the origin of hepatocellular carcinoma.

Fulminant hepatitis after flutamide treatment

Two cases of severe acute hepatitis in patients taking flutamide for metastatic prostatic carcinoma are reported. Jaundice and marked increase in aminotransferases occurred after 6-8 weeks of treatment. Continuation of flutamide administration was associated with the development of hepatic encephalopathy and a marked prolongation of prothrombin time. One of the patients died of acute liver failure and the other survived after prolonged hospitalization. Rechallenge was not performed because of the severity of the clinical picture. Liver histology showed extensive hepatic necrosis. These two cases strongly suggest that flutamide, in addition to its cholestatic side effects, can induce acute hepatitis potentially with a fulminant and lethal course. Journal of Hepatology.

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

Summary.  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‐(+).

Diastolic myocardial dysfunction does not affect survival in patients with cirrhosis.

Left ventricular diastolic dysfunction (DDF) has been considered as a component of cirrhotic cardiomyopathy. The clinical significance of DDF in cirrhotics has not been clarified. We prospectively evaluated the echocardiographic‐Doppler, tissue‐Doppler (TDI) findings of left ventricular function and survival in cirrhotics with or without DDF. Seventy‐six cirrhotics without endogenous heart disease were included. DDF was diagnosed by mitral inflow Doppler parameters and diastolic myocardial velocities. Assessments of demographics, liver dysfunction, laboratory, echocardiographic systolic/diastolic indices, TDI of mitral annular motion and M‐mode echocardiography were recorded. Patients were followed‐up for a median of 25 months (15–40). DDF was diagnosed in 51 (67%) patients. Patients with compared with those without DDF had significantly older age and higher pulse rate as well as more frequently severe ascites, greater aortic root diameter and interventricular septal thickness. There was no difference in systolic myocardial function between two groups. Patients with DDF had a trend for worse survival (long rank, P = 0.094). A multivariate analysis showed that age, MELD and sodium but no DDF were predictive of death. DDF is prevalent in advanced cirrhosis and is associated with severe ascites. Systolic myocardial function and mortality do not seem to be strongly affected by the presence of DDF.

Bevacizumab in the treatment of hereditary hemorrhagic telangiectasia.

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is a rare multisystem vascular disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations predisposing to shunting and hemorrhage. Angiogenesis has been implicated in the pathogenesis of HHT and therefore angiogenesis inhibitors appear to be the most promising agents. A literature search was performed to identify all articles reporting bevacizumab, a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). We focused on the HHT pathogenesis, mechanism of action of the drug, its impact on the HHT symptoms and safety profile. Areas covered: Systemic intravenous administration of bevacizumab improves the frequency and intensity of epistaxis, gastrointestinal (GI) bleeding episodes and liver arteriovenous malformations consequences. The safety profile of the systematic administration of the drug appears to be excellent with hypertension as the unique adverse effect reported so far. Its intranasal administration significantly decreases frequency and severity of nosebleeds and blood transfusion requirements. Expert opinion: In the absence of randomized controlled trials in HHT, criteria of selecting patients and formal recommendations for treatment are lacking. For life-threatening epistaxis requiring blood transfusion, topical treatment with bevacizumab may be beneficial. Systemic treatment with bevacizumab is promising in symptomatic patients with organ involvement and life-threatening conditions.

Hepatitis B Surface Antigen Variant with Multiple Mutations in the a Determinant in an Agammaglobulinemic Patient

ABSTRACT A patient with agammaglobulinemia developed acute hepatitis that progressed to chronic liver disease with high levels of hepatitis B virus (HBV) DNA in the absence of detectable HBsAg. Sequencing of the a determinant region of HBsAg revealed multiple amino acid substitutions that, unusually, also included a substitution at position 122 that defines subtype specificity. All of these mutations had a profound effect on the antigenicity of this region, which led to the complete failure of variant detection by commercially available routine diagnostic assays or laboratory-based monoclonal antibody assays.