Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.

BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

Comparison of acoustic radiation force impulse imaging with the convex probe 6C1 and linear probe 9L4.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a noninvasive method to detect liver fibrosis. The aims of the study were to evaluate the difference between 2 different probes, 6 C1 and 9 L4, and to study inter- and intraobserver reproducibility for the probes. METHODS: We enrolled 100 patients in this cross-sectional comparative study. All patients underwent liver stiffness measurement with both probes. Intraobserver, interobserver, intralobe, and interlobe agreement was analyzed using the intraclass correlation coefficient. RESULTS: A significant difference in success rates was observed for both probes between the right and left liver lobes. A success rate of 91% was observed in the right liver lobe compared with 77% in the left liver for the convex probe (P = .007), and 91% vs 68% for the linear probe (P < .001). There was a significant correlation in ARFI-shear wave velocity (ARFI-SWV) between both probes in the right liver lobe (P = .01; r = .508) and in the left liver lobe (P = .05; r = .278); however, there was no significant correlation in ARFI-SWV between the liver lobes for both probes (convex probe r = .19 P = .112; linear probe r = .144 P = .23). Good or excellent inter- and intraobserver was detected for both probes. Poor agreement was found only for the interobserver agreement in the left lobe with the convex probe (ICC = .320). CONCLUSION: ARFI can be performed successfully with both probes in both liver lobes. There was no significant correlation in ARFI between the liver lobes for both probes; however, the right liver lobe should be favored. Standardization of the procedure is needed for the comparability of different studies.

Anal chromoendoscopy using gastroenterological video-endoscopes: A new method to perform high resolution anoscopy for diagnosing intraepithelial neoplasia and anal carcinoma in HIV-infected patients.

Introduction Anal carcinoma represents an increasing problem in HIV-infected patients. Anal intraepithelial neoplasia (AIN), the precursor lesion, is currently diagnosed by high-resolution anoscopy (HRA) using optical magnification derived from gynecological colposcopy. This prospective study evaluates anal chromoendoscopy (ACE) using standard gastroenterological video-endoscopes in diagnosing AIN. Methods After clinical examination, proctoscopy and surface staining with acetic acid followed by Lugol's solution, ACE was performed with a mucosectomy cap on the tip of the endoscope. Biopsy specimens were collected from areas with a pathological staining pattern and from areas with normal appearance; combined results were considered as reference. Results Two hundred eleven HIV-positive patients seen between 2007 and 2013 were evaluated. Of these, 95.7 % were males, and the median age was 45 years. In 86.7 %, the mode of HIV transmission was sex among males. Combination antiretroviral treatment was applied in 75.8 %. The sensitivity of ACE in diagnosing AIN was 0.85, the specificity was 0.55, the positive predictive value was 0.50, and the negative predictive value (NPV) was 0.87. Diagnostic performance increased in individuals with high-grade lesions (NPV: 0.99) and in the second study period from 2011 to 2013. Side effects were rare and of minor clinical relevance. Conclusions Anal chromoendoscopy is safe and effective in diagnosing AIN in a population of HIV-infected patients. It is particularly useful for the exclusion of high-grade lesions that have the strongest risk of progression to anal carcinoma. Therefore, ACE may become a valuable new tool to manage AIN and to prevent anal malignancy in HIV-positive patients.

Transient Elastography for the Detection of Liver Damage in Patients with HIV.

INTRODUCTION: Highly active antiretroviral therapy (HAART) is effective and well tolerated, but hepatotoxicity is relatively common. Different non-invasive methods are available for detecting liver fibrosis in patients with chronic liver disease. METHODS: Patients who were HIV positive and who had given their informed consent were included in this cross-sectional study. Transient elastography [FibroScan(®) (FS); Echosens], serum hyaluronic acid (HA), Hepascore (HS), Fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were used to detect liver fibrosis in the patients. The agreement between FS and the other methods was evaluated. To observe the hepatotoxicity of HAART, patients with chronic viral hepatitis B or C were excluded by detection of hepatitis B surface antigens and hepatitis C virus antibodies. Patients with chronic alcohol intake were excluded by measuring carbohydrate-deficient transferrin (CDT). FS correlation with the duration of therapy with protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) was evaluated. RESULTS: Overall, 203 patients were included in the study. The agreement between the different tests ranged from 64% to 77%: FS vs. HA, 72%; FS vs. APRI, 74%; FS vs. HS, 77%; and FS vs. FIB-4, 64%. After excluding patients with chronic hepatitis B or C and elevated CDT, 153 patients remained for studying the hepatotoxicity of HAART. A significant correlation of FS with the duration of medication intake was observed for PIs (P = 0.026; r = 0.18). NRTI and NNRTI therapy duration did not correlate with FS. CONCLUSIONS: The agreement between FS and other tests ranged from 64% to 77%. A significant correlation was found between liver stiffness and the duration of therapy with PIs, which underlines the known hepatotoxicity of this substance group. FUNDING: Heinz-Ansmann Foundation.

Ambulatory care for HIV-infected patients: differences in outcomes between hospital-based units and private practices: analysis of the RESINA cohort.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting. METHODS: Since 2001, the prospective multicenter RESINA study has examined the epidemiology of transmitted HIV drug resistance in Nordrhein-Westfalen, the largest federal state of Germany by population. Characteristics of patients treated in hospital-based outpatient units were compared to those of patients treated in medical practices. Longitudinal data of all participants are being followed in a cohort study. RESULTS: Overall, 1,591 patients were enrolled between 2001 and 2009 with follow-up until the end of 2010. Of these, 1,099 cases were treated in hospital-based units and 492 in private practices. Significant differences were found with respect to baseline characteristics. A higher rate of patients with advanced disease and non-European nationality were cared for in hospital units. Patients in medical practices were predominantly Caucasian men who have sex with men (MSM) harboring HIV-1 subtype B, with lower CDC stage and higher CD4 cell count. Median viral load was 68,828 c/mL in hospital-based units and 100,000 c/mL in private practices (P = 0.041). Only median age and rate of transmitted drug resistance were not significantly different. After 48 weeks, 81.9% of patients in hospital units and 85.9% in private practices had a viral load below the limit of detection (P = 0.12). A similar result was seen after 96 weeks (P = 0.54). Although the baseline CD4 cell count was different (189.5/µL in hospital units and 246.5/µL in private practices, P <0.001), a consistent and almost identical increase was determined in both groups. CONCLUSIONS: The RESINA study covers a large HIV-infected patient cohort cared for in specialized facilities in Germany. Despite significant differences of patients' baseline characteristics in hospital-based units compared to medical practices, we could not find significant differences in treatment outcome up to 2 years after the initiation of HAART.

Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference.

AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan© (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this study. All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixty-eight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs. 482/606 (79.5%), P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.

Genetic variants of the bile salt export pump: inducers and modifiers of liver diseases.

The bile salt export pump (BSEP, ABCB11) is the major transporter protein for the excretion of bile salts into bile. Here we describe a spectrum of BSEP-dependent effects on the course of liver diseases, and present two mutations that differentially affect total bile acid output and the biliary bile acid profile. According to the clinical course of affected children, low bile acid output but a normal profile was less harmful than higher output in combination with changes in the ratio of chenodeoxycholic acid to cholic acid. On the other hand, the common BSEP polymorphism V444A (c.1331T>C; allele frequency 65%) emerged as an independent predictor of the success rate in patients with chronic hepatitis C treated with pegylated interferon/ribavirin. This association between bile acid transport and hepatitis C may be due to interference of bile acids with viral replication, interferon signaling or antiviral proteins.

High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe.

The indication for antiviral treatment of patients with chronic hepatitis B is based on serum HBV DNA levels, transaminases, and histological grade and stage. The relation of liver fibrosis and inflammation to ALT activity in chronic hepatitis B infection was investigated in a nonendemic, European setting. A total of 253 patients with chronic hepatitis B who had undergone liver biopsy at the Clinic of Gastroenterology, Hepatology, and Infectious Diseases, Düsseldorf,Germany over the past 19 years (1990­2009) were evaluated. Thirty-nine patients had persistently normal transaminases, 86 patients had ALT with 1­2 x ULN (upper limit of normal) and 128 patients had ALT >2 x ULN. Liver fibrosis or inflammation was defined as significant for stages or grades ≥ 2 according to the Desmet/Scheuer score. Significant liver fibrosis (F ≥ 2)was found in 36%, cirrhosis in 18%, and significant inflammation (G ≥ 2) in 27% of patients with normal transaminases. There was no difference in the stage of liver fibrosis and the frequency of cirrhosis between patients with normal and elevated transaminases. The most important factor associated with the presence of cirrhosis in multivariate analysis was age ≥ 40 years (P < 0.003). If concomitant factors like elevated GGT or male sex were furthermore present high prevalences of significant liver disease were found. The data indicate that, in a European setting, patients with chronic hepatitis B infection, and normal transaminases frequently have significant liver fibrosis or cirrhosis.Therefore, liver biopsy or liver stiffness measurement (LSM) should be performed in these patients to determine the stage of liver fibrosis.

Liver fibrosis in recessive multicystic kidney diseases: transient elastography for early detection.

Cystic renal diseases are characterized by intrarenal cysts of different size and number. Further important diagnostic criteria include, e.g., liver fibrosis. The latter represents a significant cause of morbidity and mortality in autosomal-recessive polycystic kidney disease (ARPKD), whereas patients with autosomal-dominant polycystic kidney disease (ADPKD) can develop hepatic cysts without fibrosis. We report the use of transient elastography [FibroScan®, (FS)] for early and noninvasive detection of increased liver stiffness as marker of liver fibrosis. Compared with matched healthy controls, ADPKD patients (n = 7) showed no significant difference in liver stiffness (5.3 kPa vs. 4.5 kPa; ns). ARPKD patients (n = 7) had significantly increased median liver stiffness compared with controls (12.0 kPa vs. 4.5 kPa, p = 0.002) and ADPKD patients (12.0 kPa vs. 5.3 kPa, p = 0.002). Conventional ultrasound revealed evidence of liver fibrosis in only four of seven ARPKD patients (57%) compared with 100% detection by FS. Additional laboratory examinations showed no pathologic liver parameters. In conclusion, our data found FS to be a valuable, sensitive, and noninvasive new tool for early evaluation of liver fibrosis in cystic kidney diseases. This could facilitate diagnosis, monitoring, and management of liver involvement in ARPKD or any other cystic kidney disease.

Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage.

UNLABELLED: Transient elastography [FibroScan (FS)] is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis in patients with chronic hepatitis. Whether FS is useful in the detection of preexisting liver fibrosis/cirrhosis in patients presenting with acute liver damage is unclear. Patients with acute liver damage of different etiologies were analyzed. Liver stiffness was measured during the acute phase of the liver damage and followed up to the end of the acute phase. A total of 20 patients were included in the study. In 15 of the 20 patients, initial liver stiffness values measured by FS during the acute phase of the liver damage were suggestive of liver cirrhosis. However, none of these 15 patients showed any signs of liver cirrhosis in the physical examination, ultrasound examination, or liver histology [performed in 11 of 15 (73%) patients]. A significant difference was observed in the initial bilirubin levels (5.8 +/- 6.5 mg/dL versus 15.7 +/- 11.8 mg/dL; P = 0.042) and age (32.4 +/- 17.5 years versus 49.7 +/- 15.8 years; P = 0.042) between patients with liver stiffness below or above 12.5 kPa. Six patients with initially high liver stiffness were followed up to abatement of the acute hepatitic phase; in all of them, liver stiffness values decreased to values below the cutoff value for liver cirrhosis. CONCLUSION: Transient elastography frequently yields pathologically high values in patients with acute liver damage and is unsuitable for detecting cirrhosis/fibrosis in these patients.

Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis C virus infection.

BACKGROUND: Treatment options for hepatitis C have developed rapidly in the past decade. The current treatment of choice is a combination of pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin. With the development of more therapy options, patients who failed in prior therapy hope to clear hepatitis C virus by undergoing a more effective retreatment regime. In this report, we investigated response rates to combination therapy [standard IFN-alpha or PEG-IFN-alpha and ribavirin] in patients who relapsed or failed in prior therapy. METHODS: Ninety-three patients were included in this retrospective study. All patients failed to previous IFN-alpha monotherapy (n=55) or to a combination of standard IFN-alpha and ribavirin (n=38). Fifty-nine patients were nonresponders and 34 were relapsers. Thirty-five patients were retreated with standard IFN-alpha plus ribavirin and 58 received PEG-IFN-alpha combination therapy. RESULTS: Sustained virologic response (SVR) was induced in 31% of all patients. The highest SVR rate (58%) was observed in relapsers to standard IFN-alpha combination therapy who were retreated with PEG-IFN-alpha combination therapy. The SVR rate in relapsers to standard IFN-alpha monotherapy who received a standard IFN-alpha combination therapy was 50%. Relapsers responded in a significantly higher proportion to retreatment than nonresponders (56% vs. 17%, P<0.001). Relapse to previous therapy was identified as an independent predictor for therapy response. The lowest SVR rate was observed in nonresponders to standard IFN-alpha combination therapy who were retreated with PEG-IFN-alpha combination therapy (1/26; 4%). CONCLUSIONS: In relapsers, retreatment with the most effective therapy regime to date a combination of PEG-IFN-alpha and ribavirin, is promising. However, retreatment with PEG-IFN-alpha combination therapy in nonresponders to standard IFN combination therapy is not effective.

Trends of prevalence of primary HIV drug resistance in Germany.

BACKGROUND: Primary HIV drug resistance (PDR) is associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART). The aim of the study was to observe the trend of prevalence of PDR between 2001 and 2005. METHODS: In a prospective multicentre study in the state of Nordrhein-Westfalen, Germany, 831 treatment-naive chronically HIV-infected patients underwent genotypic resistance testing. RESULTS: Six hundred and forty (77%) of them were male. Two-thirds of the patients (558, 67%) were infected with HIV subtype B. PDR was found in 75 of 831 [9%; 95% confidence interval (CI) 7.1-10.9] cases entering the study between January 2001 and December 2005. An increasing trend of PDR was found from 2001 (4.8%; CI 2.1-9.4) to 2005 (9.0%; CI 5.4-12.6; P = 0.08). A significant tendency to higher PDR was observed for ethnicity other than Caucasian (P = 0.04), HIV subtypes other than B (P = 0.02) and transmission routes other than homosexual (P = 0.03). CONCLUSIONS: A non-significant increase in prevalence of PDR was observed from 2001 to 2005. A significant trend to higher PDR rate was detected in non-Caucasian patients, patients infected with non-B subtypes, and in patients with risk factors for acquisition of HIV other than homosexual transmission. Based on the fact that there is a trend to higher PDR rate, resistance testing in untreated HIV-infected patients starting HAART becomes more important in clinical routine. The identification of patient subgroups with a remarkable risk of PDR makes continuous monitoring of PDR mandatory.

Treatment of chronic hepatitis delta with pegylated interferon-alpha2b.

BACKGROUND/AIMS: Chronic hepatitis D is difficult to treat. The present pilot study investigated the efficacy and tolerability of pegylated (PEG)-interferon (IFN)-alpha2b in chronic hepatitis D. PATIENTS AND METHODS: Twelve patients with chronic hepatitis D were prospectively treated with 1.5 microg/kg PEG-IFN-alpha2b for 48 weeks and followed for 24 weeks. Sustained response (SR) was defined as undetectable hepatitis delta virus (HDV) RNA by reverse transcriptase-polymerase chain reaction and normalization of alanine aminotransferase (ALT) at 6 months after treatment. Investigations included HDV RNA kinetics, determination of hepatitis B virus (HBV) and HDV genotypes and histological evaluation. RESULTS: An SR was achieved in two out of 12 of patients (17%). The negative predictive value of a less than 3 log HDV RNA decrease at month 6 was 100%. The positive predictive value of a more than 3 log HDV RNA decrease at month 6 was 67%. A marked ALT reduction at the end of treatment was observed in responders and nonresponders. Ishak histological score was comparable at baseline and significantly improved in responders compared with nonresponders at the end of follow-up (13.5 vs. 8.0; P<0.02). CONCLUSION: The present study indicates that PEG-IFN-alpha2b is a promising treatment option in chronic hepatitis D. Nonresponders could be identified by a less than 3 log decrease of HDV RNA at 6 months of treatment.

Predictors of short-term success of antiretroviral therapy in HIV infection.

OBJECTIVES: The success of highly active antiretroviral therapy (HAART) in HIV infection may be influenced by numerous host factors. There is a lack of data presenting a combined assessment of a variety of these parameters for treatment efficacy in clinical routine practice. METHODS: Different indices of therapeutic drug monitoring (TDM) were evaluated prospectively in the context of self-reported adherence, health-related quality of life and social determinants, as measured by a questionnaire. RESULTS: A total of 210 individuals were studied between 2002 and 2004, 77% were males, mean age was 44 years, mean CD4 count was 336 cells/mm3 and 63% had a viral load < 50 copies/mL. In univariate analysis, baseline viral load, unscheduled drug levels, a 4 h pharmacokinetic profile (PK-P) at a scheduled visit and self-reported complete adherence within the previous 2 weeks were significantly associated with virological success of HAART at 12 weeks. At 24 weeks, only baseline viral load, the 4 h PK-P and adherence were significantly associated with HAART efficacy. In multivariate analysis, baseline viral load, adherence, unscheduled drug levels, trough levels at a visit with appointment as well as the 4 h PK-P were significantly associated with virological success at 12 weeks. At 24 weeks, only adherence was significantly linked to outcome. The other parameters were not found to have an impact on treatment efficacy. CONCLUSIONS: TDM and self-reported adherence were independently predictive of short-term HAART success in this prospective study. Unscheduled drug measurements provided similar diagnostic information as a 4 h PK-P. Thus, we propose the use of unscheduled drug level monitoring and self-reported adherence to help identify patients with elevated risk of virological failure.

SEN virus has an adverse effect on the survival of HIV-positive patients.

BACKGROUND: Patients infected with HIV are often coinfected with other viruses. OBJECTIVE: To investigate the effect of SEN virus (SENV) strains D and H on mortality in HIV-positive patients. METHODS: A total of 217 HIV-positive patients were analysed retrospectively after first presentation and blood sampling (January 1997 to July 1997) and the effect of coinfection with SENV-D and SENV-H on survival was examined. Analysis periods were the time from blood sampling to the end of follow-up, and the time from diagnosis of HIV infection to the end of study follow-up. SENV-H DNA was measured quantitatively. Prevalences of SENV-D and SENV-H were compared with those in 112 healthy blood donors. RESULTS: SENV prevalence was significantly higher in HIV-positive patients than in controls (56/217 and 12/112, respectively; P < 0.001). SENV positivity had no influence on survival, but a significant negative influence of SENV-H on survival was observed when SENV-H DNA was > 530 copies/ml, which was the mean SENV-H DNA level found in HIV-negative controls. This adverse effect was found for both studied time periods in a Kaplan-Meier analyses. A multivariate Cox regression analysis, including CD4 cell count, Centers for Disease Control and Prevention stage, age, sex, HIV RNA, highly active antiretroviral therapy and hepatitis C virus status, revealed that a high SENV DNA level was an independent risk factor or indicator for adverse disease outcome. CONCLUSION: SENV infection is common in HIV-positive patients. High SENV-H DNA levels were predictive for poor survival in HIV-positive patients.

SEN virus seroprevalence in HIV positive patients: association with immunosuppression and HIV-replication.

BACKGROUND: Patients infected with HIV are often co-infected with other viruses. SEN virus (SENV) was isolated from a HIV positive patient with intravenous drug use and post-transfusion hepatitis. SENV strains D and H seem to be relevant for the development of post-transfusion hepatitis. We compared the prevalence of SENV strains D and H and the viral load of SENV H in HIV-infected patients with healthy blood donors. The results were correlated with clinical markers such as HIV stage, CD4 cell count, HIV-RNA positivity, HAART or the transmission mode in HIV infected individuals. OBJECTIVES: Blood samples of 143 HIV-positive patients were analysed and compared with a control group of 122 healthy blood donors. SENV D and -H was detected by PCR. RESULTS: SENV was detectable in 15.4% (22/143) of HIV-positive patients compared to 10.4% (12/122) in the control group (P=0.18). SENV H DNA-levels were significantly higher in HIV-positive patients (P=0.01). The prevalence in patients with CD4 cells less than 200/mm(3) was 31% (13/42), compared to 12.3% (8/65) in cases with CD4 cells between 200 and 500/mm(3), and 2.8% in cases with CD4 cells above 500/mm(3) (P=0.002 for CD4 cells <200 versus CD4 cells >200, P=0.031 for CD4 cells <500 versus CD4 cells >500). Prevalence of these strains was not significantly influenced by CDC stages. SENV was detected significantly more frequent in patients with detectable HIV-RNA (P=0.005). Patients undergoing HAART were significantly less frequent positive for SENV D or -H (P=0.029) than patients without HAART. In a multivariate analysis using a logistic regression model HIV-RNA positivity and CD4 cell count were identified as independent factors for SENV prevalence. CONCLUSION: SENV (D and H) prevalence is not significantly higher in HIV-positive patients in comparison to healthy blood donors. SENV prevalence depends on CD4 cell count and HIV-RNA.

Acute syphilitic blindness in an HIV-positive patient.

This case report describes a rare manifestation of syphilis. An HIV-positive patient with severe immunosuppression presented with rapid loss of vision due to eye involvement of Treponema pallidum infection. The ophthalmologic examination on admittance showed a chorioretinitis, an uveitis, and a swollen optical disc of both eyes. Reconstitution of vision after application of intravenous penicillin occurred within 3 weeks. Despite low HIV prevalence in central Europe, behaviors that promote transmission of HIV and other sexually transmitted diseases tend to increase. The clinical presentation of syphilis may be atypical and the rate of complications is often higher in HIV-infected patients. Thus, Treponema pallidum infection should be considered in immunosuppressed HIV-positive patients presenting with chorioretinitis. Patients should receive treatment similar to that for neurosyphilis if there is suspicion of involvement of the central nervous system.

Is ultrasound a useful adjunct for assessing malaria patients?

The value of ultrasonography as an adjunct for diagnosis and monitoring malaria was investigated. In all, 118 patients (male/female 65/53; age 2-78 years, median 29 years) with malaria underwent a standardised abdominal ultrasound examination at baseline. In 62 out of 118 patients, ultrasonography was repeated 21 days later. In the results at baseline, huge splenomegaly with firm organ consistency, consistent with hyperreactive malarious splenomegaly syndrome, was observed in two Cameroonese children. In the other 116 patients, the most common finding was non-specific splenomegaly (96/116, 82.76%), occurring more frequently in non-immune patients (71/78, 91.03%) than in patients who had grown up in malaria-endemic areas (25/38, 65.79%; P<0.002). No correlation was found between liver or spleen size and any clinical parameter. The results on day 21 show that, although splenomegaly after therapy persisted more frequently in patients with malaria recrudescence or relapse (8/8, 100%) than in patients cured (32/54, 59.26%; P<0.0421), the practical value of this finding is questionable. Ultrasonography cannot be regarded as a first-line diagnostic method in patients with malaria.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration.

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-alpha) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV. METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA. RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV (50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=0.05). CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy. Response rate of SENV to the combination therapy depends on SENV DNA level.

SEN virus infection.

The SEN virus (SEN-V) belongs to a recently discovered group of DNA viruses whose members (SEN-V-D and SEN-V-H) are associated with post-transfusion hepatitis. It is a single-stranded circular, non-enveloped DNA virus of approximately 3600 to approximately 3800 nucleotides with at least three open reading frames (ORFs). Eight different strains of SEN-V have been identified and provisionally classified as members of the Circoviridae family, a group of small, single-stranded, non-enveloped circular DNA viruses that includes the TT virus (TTV), TUS01, SANBAN, PMV and YONBAN. Prevalences in different populations show great variability with marked differences between different countries and groups. Although parenteral transmission is very likely, other routes of transmission cannot be excluded. Mother to infant transmission has been demonstrated. The effect of SEN-V on chronic liver diseases has been studied. The influence of SEN-V on the response to HCV therapy was investigated in three studies, with contradictory results. Data for other acute and chronic liver diseases are sparse. Further studies are needed to define the pathogenesis and clinical importance of SEN-V infection.