Renal cell carcinoma with unusual metachronous metastasis up to 22 years after nephrectomy: two case reports.

INTRODUCTION: Renal cell carcinoma is the third most common malignant tumor in the urogenital tract. An estimated 25% of renal cell carcinomas are in stage IV when diagnosed. The 5-year-survival with stage IV is about 20%. Late metastases are found after an extended disease-free interval up to 20 years after primary nephrectomy. CASE PRESENTATION: Here, we present two cases with late-onset metastasis of renal cell carcinoma with different clinical presentations. The first patient, an 88-year-old Caucasian man, presented with bleeding of the upper gastrointestinal tract. Biopsies taken from the duodenal bulb showed a tumor compatible with a solitary metastasis from renal cell carcinoma 22 years ago. The second patient, a 79-year-old Caucasian man, consulted our gastroenterological department with results of an outpatient computed tomography scan with multiple suspected tumor areas in the liver, omentum, thyroid, and mediastinum. A computed tomography-guided liver biopsy was performed that showed a clear-cell tumor consistent with a metastasis of the renal cell carcinoma 17 years ago. CONCLUSION: Both cases show that patients with a history of renal cell carcinoma should be followed up for a longer time than patients with other malignant tumors.

Agenesis of dorsal pancreas associated with pancreatic neuroendocrine tumor: a case report and review of the literature.

BACKGROUND: Agenesis of the dorsal pancreas is very rare. Less than 70 cases have been reported to date. Some of these cases had an association with a tumor. The literature of agenesis of the dorsal pancreas and agenesis of the dorsal pancreas-associated pancreatic neoplasia is limited. Here we report the second case of a pancreatic neuroendocrine tumor in a setting of agenesis of the dorsal pancreas. CASE PRESENTATION: A 71-year-old man, originally from North Africa, with a history of insulin-dependent diabetes mellitus, presented with a 2-month history of nonspecific abdominal symptoms. Contrast-enhanced computed tomography demonstrated an almost 3 cm round, quite well-defined and homogeneous tumor formation in the area between the neck and absent body and tail of his pancreas. The mass was confirmed by endoscopic ultrasound. Our patient underwent computed tomography-guided biopsy of the mass which provided proof of a neuroendocrine tumor. He underwent pancreas resection because of the presence of a neuroendocrine tumor. Seven months later his glycated hemoglobin increased from 6.9 to 8.7%. CONCLUSIONS: Diagnosis of agenesis of the dorsal pancreas is based on imaging techniques like computed tomography, magnetic resonance cholangiopancreatography, or endoscopic ultrasound. Endoscopic ultrasound-guided fine-needle aspiration can be helpful for the histological diagnosis of the tumor. The hypothesis of the association between pancreatic neoplasia and agenesis of the dorsal pancreas leads us to the suggestion that every patient with diagnosed agenesis of the dorsal pancreas should be observed with a focus on the early detection of potential malignancy.

Point Shear Wave Elastography by Acoustic Radiation Force Impulse Quantification in Comparison to Transient Elastography for the Noninvasive Assessment of Liver Fibrosis in Chronic Hepatitis C: A Prospective International Multicenter Study.

PURPOSE: The aim of the present prospective European multicenter study was to demonstrate the non-inferiority of point shear wave elastography (pSWE) compared to transient elastography (TE) for the assessment of liver fibrosis in patients with chronic hepatitis C. MATERIALS AND METHODS: 241 patients with chronic hepatitis C were prospectively enrolled at 7 European study sites and received pSWE, TE and blood tests. Liver biopsy was performed with histological staging by a central pathologist. In addition, for inclusion of cirrhotic patients, a maximum of 10 % of patients with overt liver cirrhosis confirmed by imaging methods were allowed by protocol (n = 24). RESULTS: Owing to slower than expected recruitment due to a reduction of liver biopsies, the study was closed after 4 years before the target enrollment of 433 patients with 235 patients in the 'intention to diagnose' analysis and 182 patients in the 'per protocol' analysis. Therefore, the non-inferiority margin was enhanced to 0.075 but non-inferiority of pSWE could not be proven. However, Paired comparison of the diagnostic accuracy of pSWE and TE revealed no significant difference between the two methods in the 'intention to diagnose' and 'per protocol' analysis (0.81 vs. 0.85 for F ≥ 2, p = 0.15; 0.88 vs. 0.92 for F ≥ 3, p = 0.11; 0.89 vs. 0.94 for F = 4, p = 0.19). Measurement failure was significantly higher for TE than for pSWE (p = 0.030). CONCLUSION: Non-inferiority of pSWE compared to TE could not be shown. However, the diagnostic accuracy of pSWE and TE was comparable for the noninvasive staging of liver fibrosis in patients with chronic hepatitis C.

Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI) for the Determination of Liver Stiffness Using Transient Elastography as a Reference in Children.

PURPOSE: Transient elastography (Fibroscan(©); (FS)) and acoustic radiation force impulse imaging (ARFI) represent noninvasive, user-friendly and quick methods providing an objective and reproducible measure of liver stiffness. The aim of the study was to evaluate cut-off values and performance of ARFI measurements in children using transient elastography as a reference. METHODS/PATIENTS: A total of 198 children were enrolled in this study. All patients underwent liver stiffness measurements with FS (FS-LS) as well as ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was studied. RESULTS: Significantly higher rates of successful measurements were found for ARFI compared to FS (198/198 (100%) vs. 160/198 (80.8%); p<0.001). ARFI-SWV correlated significantly with FS-LS (r=0.751, p=0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.19+0.15 m/s for patients with FS-LS<7.6 kPa); 1.34+0.22 m/s for patients with 7.613.0 kPa). ARFI-SWV cut-off values were identified for no significant fibrosis (1.31 m/s; sensitivity 61.8% and specificity 79.5%) and for liver cirrhosis (1.63 m/s; sensitivity 70.0% and specificity 97.4%). The median values of liver stiffness measured by FS were age-dependent in 90 children without liver diseases with 4.8, 5.6, and 5.7 kPa in children 0-5, 6-11, and 12-18 years, respectively.

Cholestatic liver diseases from child to adult: the diversity of MDR3 disease.

The phospholipidfloppase MDR3 (gene symbol: ABCB4) is expressed in the canalicular membrane of hepatocytes and mediates the biliary excretion of phosphatidylcholine, which is required for the formation of mixed micelles in bile. Several mutations of ABCB4 have been identified, which cause cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 3 (PFIC-3), intrahepatic cholestasis of pregnancy (ICP) and the low phospholipid associated cholelithiasis syndrome (LPAC). Here, we report on four new (S1076N; L 23Hfs16X; c.286 + 1G > A; Q 1181E) and one known (S27G) MDR3 mutations in eight patients of three families. The patients presented with a wide spectrum of liver diseases. The clinical presentation and decisive laboratory findings or the association to a trend-setting family history led to the identification of the genetic background in these patients. Even the same mutation may be associated with varying disease progression.

[Diagnosis of focal liver lesions in cirrhotic patients: comparison of contrast-enhanced ultrasound using sulphur hexafluoride (SF6) microbubbles and MRI using Gd-EOB-DTPA]. / Vergleich der kontrastverstärkten Sonografie und der MRT mit Gd-EOB-DTPA zur Diagnostik fokaler Leberläsionen bei Patienten mit Leberzirrhose.

AIM: The diagnostic accuracies of contrast-enhanced sonography and hepatobiliary contrast-enhanced MRI of the liver in evaluating focal liver lesions in patients with liver cirrhosis were compared. MATERIAL AND METHODS: In 33 patients (25 men, 8 women, mean age 63.2 ± 11.2 years) MRI of the liver using Gd-EOB-DTPA (Primovist®, Bayer Schering Pharma, Berlin) was performed. Axial T(2)-weighted, unenhanced T(1)-weighted and enhanced T(1)-weighted scans during arterial, portal venous and late phases were acquired, followed by coronary T(1)-weighted and axial fat-suppressed T(1)-weighted scans 15 minutes post contrast application. In all patients within 4 weeks contrast-enhanced sonography using sulfur hexafluoride microbubbles (SonoVue®, Nycomed, Germany) was obtained. RESULTS: Cirrhosis of the liver was related to viral infection in 45.4% and to alcoholism in 39.4%. All hepatic lesions were confirmed by histologic examination. Sensitivity and specificity of MRI were 90.2% and 83.3%, compared to contrast-enhanced sonography with 92.7 % and 50 %, respectively. Positive and negative predictive values were 97.4% and 55.5 % for MRI and 90.5% and 50% for contrast-enhanced sonography, respectively. DISCUSSION: In this retrospective study MRI using Gd-EOB-DTPA as well as contrast-enhanced sonography using sulfur hexafluoride microbubbles gave excellent results in detecting HCC in patients suffering from liver cirrhosis. Although the specificity was higher for MRI, the accuracy showed no significant difference between these two imaging techniques.

Retrospective analysis of chronic hepatitis D in a West German University Clinic over two decades: migratory pattern, prevalence and clinical outcome.

BACKGROUND/AIMS: Epidemiology, clinical features and long term-course of chronic hepatitis D were addressed in a non-endemic Central European area. METHODS: Sixty-seven patients with chronic hepatitis D were identified among 1307 HBsAg carriers at the university hospital Düsseldorf during two decades (1989 - 2008) and followed for a mean of 7 +/- 6 years. Forty-one of these were treated with IFN-alfa for at least six months. RESULTS: Hepatitis D prevalence increased from 4.1 to 6.2 % among HBsAg carriers during the two decades (p < 0.06). Patients originating from the former Soviet Union (32.1 vs. 46.2 %) and Africa (0 vs. 17.9 %) became more frequent whereas the prevalence of patients from Southern Europe declined (46.5 vs.17.9 % p < 0.03). The time span between the diagnosis of hepatitis B and D was 4.8 +/- 7 years (p < 0.0001). A sustained virological response to interferon-alfa was achieved in 19.5 % of the patients. The yearly incidence rates for death, HCC and complications were 3.2 %, 2.7 % and 8 % among patients with liver cirrhosis. Estimated survival and complication-free survival during 12 years were 72 % and 45 % in cirrhotic compared to 100 % in non-cirrhotic patients (p < 0.008 and p < 0.0001, respectively). CONCLUSION: Hepatitis D in western Germany appears to be on the increase and has a migration background that should be considered in clinical practice. Clinical outcome and response to IFN are as poor as in endemic regions, indicating the need to improve early diagnosis.

Wireless capsule endoscopy for the detection of small bowel diseases in HIV-1-infected patients.

BACKGROUND AND AIMS: In HIV-infected patients, manifestations of the disease are common in the gastrointestinal tract. The objective of our study was to evaluate the diagnostic yield of the Given(R) Video Capsule System (Given Imaging, Yoqneam, Israel) in these patients. METHODS: After the exclusion of GI-tract stenosis by anamnestic exploration, 49 patients were included into the study. Stratification: Group A (n = 19): HIV-positive, CD4 cell count < 200/microl, gastrointestinal symptoms present. Group B: HIV-positive, CD subset4 < 200/microl, without gastrointestinal symptoms (n = 19 Group) C: healthy volunteers (n = 11). RESULTS: In group A there was a total of 30 pathological findings, 15 of which had therapeutic implications. In group B, there was a total of 22 pathological findings, 5 relevant for therapy. In group C there was a total of 13 pathological findings, 3 with therapeutic relevance. In 89% (group A) vs. 26% (group B), pathological findings were detected distal to the ligament of Treitz (p = 0.001). All capsules were recovered without any complication after 12 to 96 h from the stool. CONCLUSION: Wireless capsule endoscopy of the small intestine should be considered for HIV-infected patients with marked immunosuppression and gastrointestinal symptoms.

SEN Virus infection in HIV/HCV coinfected patients.

BACKGROUND: Chronic Hepatitis C Virus (HCV) infection is currently one of the most relevant coinfections in HIV positive patients. The influence of SEN Virus (SENV) on the outcome of HCV therapy in HIV/HCV coinfected patients who underwent combination therapy with pegylated interferon (PEG-IFN) and ribavirin is unclear. METHODS: SENV DNA was determined by polymerase chain reaction in 67 HIV/HCV coinfected patients, 77 HIV monoinfected patients, 95 treatment naive HCV monoinfetcted patients, and 122 healthy blood donors. Quantitative analysis was done for SENV H DNA. RESULTS: SENV DNA was detected in 8 of 67 (12%) HIV/HCV coinfected patients, in 9 of 77 (11.7%) HIV monoinfected patients, in 21 of 95 (22%) HCV monoinfected patients, and 12 of 122 (9.8%) healthy blood donors. HIV monoinfected patients showed the highest mean SENV H DNA level. The mean SENV H DNA was significantly lower in HIV/HCV coinfected patients compared to all other groups. The sustained virological response rates to combination therapy of HCV in HIV/HCV coinfected patients did not differ between patients with detectable SENV 5/8 (62.5%) and without SENV 28/59 (47.5%; p = 0.47). We found no significant difference in SENV H DNA pretreatment levels between nonresponders and responders to combination therapy (112 +/- 144 copies vs. 8 +/- 7 copies/ml; p = 0.27). CONCLUSION: Coinfection with HCV may reduce SENV H replication in HIV positive patients and results in significantly lower SENV H DNA levels in HIV/HCV coinfected patients. SENV infection has no influence on the outcome of HCV combination therapy in HIV/HCV coinfected patients.

Therapy outcome in patients with chronic hepatitis C: role of therapy supervision by expert hepatologists.

Previous large multicentre trials reported sustained virological response (SVR) rates of 45-80% in chronically infected hepatitis C virus (HCV) patients. However, it is unclear whether such a treatment success is also achieved in daily routine and to what extent it depends on expert hepatological supervision. This was retrospectively analysed in patients presenting at our outpatient department during May 1997 and March 2004 and receiving at least one treatment dose. A total of 302 treatment-naive HCV patients [72% genotypes 1 or 4 (n = 215), 25% genotypes 2/3 (n = 78) and 3% undetermined genotype (n = 9)] were included in the analysis. Out of these, 196 patients consulted an expert hepatologist at least once every 3 months during treatment [regular visitors (RV)], whereas in 106 patients treatment was performed and supervised by a general practitioner (irregular visitors). Both patient groups did not differ in their baseline characteristics. However, the virological response rates at the end of treatment (ETR; 146/196, 74%vs 51/106, 48%, P < 0.001) and 6 months thereafter (SVR; 129/196, 66%vs 36/106, 34%, P < 0.001) were significantly higher in RV. In patients treated with pegylated-interferon (PEG-IFN)/ribavirin, this difference was statistically highly significant (P < 0.001) for HCV genotypes 1 and 4 (treated patients: SVR: 62/101, 61%vs 14/51, 27%, P < 0.001), but not for genotypes 2/3. SVR rates were also significantly better in RV with advanced liver damage [SVR 69% (22/32) vs 25% (5/20), P = 0.004]. In regular and irregular visitors treatment was discontinued in 7% (14/196) and 15% (16/106) respectively (P = 0.015). Patients with unfavourable genotypes 1 and 4 or with advanced liver damage benefit from HCV therapy supervision by a specialist, probably because of less frequent treatment interruptions or dose reductions.

[Epidemiology of primary drug resistance in chronically HIV-infected patients in Nordrhein-Westfalen, Germany, 2001-2005]. / Epidemiologie der primären Medikamentenresistenz bei chronisch HIV-Infizierten in Nordrhein-Westfalen 2001-2005.

BACKGROUND AND OBJECTIVE: Primary HIV drug resistance, characterized by mutant virus strains in untreated HIV-infected persons, is of significant epidemiological significance. Primary resistance is associated with reduced efficacy of antiretroviral therapy (ART). We determined the prevalence of primary resistance in Nordrhein-Westfalen, Germany. PATIENTS AND METHODS: Genotypic resistance testing was performed in a prospective multicenter study in chronically infected previously untreated HIV-positive patients before administration of first-line ART. Mutations were classified according to the International AIDS Society USA guidelines and the geno2pheno interpretation tool. RESULTS: Between January 2001 and December 2005, resistance testing was performed in 831 patients. 77.4% were males, the mean age was 39 years (SD: 10.5). The mean duration of diagnosis of HIV infection was 1.6 years (SD: 3.4). 32.4% of patients were at CDC stage C, mean CD4 cell count was 236 /microl (SD: 205), and mean viral load was 206,855 copies/ml (SD: 450,610). In total, resistance-associated mutations were detected in 75 patients (9.0%; 95%CI, 7.1-11.0). After inclusion of mutations E44D and V118I, resistance was identified in 99 patients (11.9%; 95%CI, 9.7-14.1). 5.4% had mutations indicating nucleoside reverse transcriptase inhibitor (NRTI) resistance (95%CI, 3.9-7.0), 3.0% had non-NRTI resistance (95%CI, 1.8-4.2), and 2.4% had protease inhibitor resistance (95%CI, 1.4-3.4), respectively. Two-class resistance was detected in 0.8% (95%CI, 0.2-1.5), three-class resistance in 0.5% (95%CI, 0.01-1.0). Mutations indicating revertant variants of resistant strains were found in 3.9% (95%CI, 2.5-5.2). Considering the variables age, gender, time since diagnosis, CDC stage, CD4 cell count, viral load, HIV subtype, ethnic origin, and HIV transmission group, no significant risk factor for the presence of primary resistance was demonstrated in univariate and mutlivariate analyses. CONCLUSION: The prevalence of primary resistant virus strains was about 10% in chronically infected ART-naive HIV-patients in the largest federal state of Germany. The majority of these patients had NRTI-associated resistance. No risk factor for the presence of primary drug resistance was identified. Because of the high prevalence and the possible impact on efficacy of drug treatment, routine genotypic resistance testing should be performed in untreated HIV-positive patients before administration of first-line ART.

[Transient elastography for diagnosing liver cirrhosis]. / Transiente Elastografie zur Diagnose der Leberzirrhose.

BACKGROUND AND OBJECTIVE: Detection of liver cirrhosis has numerous implications because of the potential sequelae of cirrhosis. Transient elastography (Fibroscan), was evaluated as a novel, non-invasive means of assessing cirrhosis by measuring liver stiffness. METHODS: 147 consecutive patients with different forms of liver disease and histologically determined stages of liver fibrosis were prospectively studied by transient elastography. 48 patients had liver cirrhosis. RESULTS: The number of transient elastographic measurements per patient was 12+/-4 (range 6 - 30). Valid elastography measurements were available for 135 out of 147 patients (92 %). The results of transient elastography correlated positively with the histological score of liver fibrosis (r = 0.8; 95 % CI: 0.72 - 0.85; p < 0.001). Areas under the receiver operating characteristic curve (AUROC) were 0.91 for > or = F3 fibrosis (95 % CI: 0.85 - 0.96) and 0.94 for cirrhosis (95 % CI: 0.90 - 0.98). Using a cut-off value of 13 kPa for detection of liver cirrhosis a sensitivity of 90 %, a specificity of 82 %, a positive predictive value of 71 % and a negative predictive value of 95 % were obtained. CONCLUSIONS: Measuring liver stiffness by transient elastography proved to be an easy method to assess liver cirrhosis. In combination with clinical signs, ultrasound and biochemical markers noninvasive diagnosis of liver cirrhosis will be further improved.

Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients.

OBJECTIVES: The insulin-sensitizer rosiglitazone is under investigation for therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about pharmacological interactions with antiretroviral (ARV) drugs. METHODS: Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective study before and at day 28 after start of treatment with 4 mg of rosiglitazone for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1, 2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for analysis. RESULTS: Twelve males and six females were assessed; mean age was 50.7 years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside reverse transcriptase inhibitors in all cases. After administration of rosiglitazone, no significant differences in Cmax, Cmin and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax of nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI) -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the geometric mean ratio (GMR) of Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9-1.0; GMR of Cmin 0.89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01). CONCLUSIONS: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is likely to reduce the bioavailability of nevirapine. Thus, routine TDM is recommended for patients treated with rosiglitazone and nevirapine. A therapy consisting of efavirenz or lopinavir seems to be without negative impact. Further studies on the interaction of rosiglitazone with ARV drugs are necessary.

Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.

BACKGROUND AND AIMS: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. PATIENTS AND METHODS: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. RESULTS: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response. CONCLUSIONS: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

Atazanavir for treatment of HIV infection in clinical routine: efficacy, pharmacokinetics and safety.

INTRODUCTION: Atazanavir (ATV) is a novel protease inhibitor that has been recently introduced into therapy of HIV infection. Currently there is little data on ATV therapy from daily practice. METHODS: In this retrospective study, we report on ATV efficacy and safety in clinical routine. Drug monitoring was performed consisting of unscheduled single measurements and a 4-hour-profile. Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were regarded as sufficient. RESULTS: Between May 2003 and April 2004, ATV treatment was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was discontinued in 10% due to side effects or malignant diseases. No significant influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell-count, and HI-viral load was seen. Virologic failure occurred in 13% of patients, all of them were PI-experienced. Pharmacokinetic data are available for 32 patients, all patients had sufficient trough levels. 30% with unboosted ATV and 21% with boosted ATV had peak plasma concentrations below the level defined as sufficient. Mean trough levels, plasma profile and AUC did not differ significantly between groups with non-boosted versus boosted ATV regimes but showed a wide inter-patient variability. CONCLUSIONS: ATV treatment of HIV-infected patients with or without a RTV booster was safe and effective in clinical routine. Drug levels were sufficient in the majority of cases. The variability of pharmacokinetic results in our sample supports therapeutic drug monitoring in patients treated with ATV.

Inhibition of cytochrome P450 3A: relevant drug interactions in gastroenterology.

Cytochrome P450 3A (CYP3A) is involved in biotransformation of more than half of all drugs currently available. Drug interactions by inhibition of CYP3A are of major interest in patients receiving combinations of drugs. Some interactions with CYP3A inhibitors also involve inhibition of the multidrug export pump, P-glycoprotein. An increasing number of adverse drug reactions might be avoided on the basis of knowledge about CYP3A substrates and inhibitors. This article summarizes some examples of such interactions relevant to gastroenterologists. Serious cases by coadministration of CYP3A inhibitors resulting in acute hepatitis, hypotension, rhabdomyolyis, torsade de pointes, sedation, or ergotism are presented: interactions with azole antifungals (ketoconazole, itraconazole, fluconazole), HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin), and grapefruit juice. In addition, 1 case is reported who presented the highest trough levels of the CYP3A substrate budesonide in serum ever measured. Practitioners have to be aware of the high potential of metabolic drug interactions when they prescribe a CYP3A inhibitor. It is wise to check carefully comedication in patients complaining of side effects with substrates of CYP3A.

Socioepidemiological data on hepatitis delta in a German university clinic--increase in patients from Eastern Europe and the former Soviet Union.

BACKGROUND AND AIMS: The relevance of chronic hepatitis delta results from its high morbidity leading frequently to rapid cirrhosis progression. The aim of the present study was the socioepidemiological characterization of patients with hepatitis delta, in order to identify patients at risk for hepatitis delta. PATIENTS AND METHODS: Clinical parameters of 36 consecutive patients with chronic hepatitis delta, seen between 1989 and 2002 at the University Hospital in Düsseldorf, were evaluated for the present study. Socioepidemiological parameters, available in 31 of these patients who returned a questionnaire, were compared to data of the population of Nordrhein-Westfalen (NRW). RESULTS: Liver cirrhosis was found in 33.3% of patients. There was a mean delay of 3 years between the diagnosis of hepatitis B and D. Patients with delta hepatitis were characterized by lower education, were more frequently unemployed, exhibited less qualified work and had less property compared to the population of NRW. 86.1% of hepatitis delta patients were immigrants to Germany. Before 1995 hepatitis delta infections were mainly seen in patients from Southern Europe (75%), whereas after 1996 predominantly patients from Eastern Europe and the former Soviet Union (53.6%; p < 0.04) contributed to the newly diagnosed cases of hepatitis delta. CONCLUSIONS: The present data underline that hepatitis delta is a severe disease. It seems reasonable to intensify screening for hepatitis delta among patients with low socioeconomic status, especially among immigrants of Eastern Europe and the former Soviet Union.

Malaria and tourism: retrospective analysis of German malaria cases imported from the Dominican Republic.

We report on malaria acquired by German tourists to formerly non-endemic tourist resorts in the Dominican Republic between July 1999 and March 2000. Falciparum malaria is endemic in the western provinces and the hinterland of the Dominican Republic. By contrast, the risk of contracting malaria has always been considered so low in the main tourist resorts in the eastern part of the country that antimalarial chemoprophylaxis was not recommended.

Successful treatment of hepatitis B virus associated polyarteritis nodosa with a combination of prednisolone, alpha-interferon and lamivudine.

Therapy of hepatitis B virus (HBV)-associated poly-arteritis nodosa is still evolving. Here we report a successful treatment with a short-term steroid administration in combination with a-interferon and lamivudine and a complete sequence analysis of the HBV genome. A 58-year-old man presented with the symptoms of mononeuritis multiplex associated in time with the onset of highly replicative hepatitis B. Polyarteritis nodosa was confirmed by biopsy. During an initial course with alpha-interferon and prednisolone no clinical improvement or hepatitis B virus seroconversion was observed. After addition of lamivudine to the protocol with fast tapering of prednisolone, HBV DNA fell to undetectable levels within 1 month and liver transaminases normalized. After 6 months of treatment HBeAg seroconversion took place, followed by HBsAg seroconversion 2 months later. Clinical symptoms of polyarteritis improved. No relapse of polyarteritis or hepatitis B was seen during the follow up of 9 months. Complete sequence analysis of the HBV genome revealed 6 nucleotide mutations but none in a relevant antigenic epitope. The present protocol of short-term prednisolone administration combined with alpha-interferon and lamivudine was effective for the treatment of HBV-related polyarteritis nodosa and may be a promising new therapeutic approach.