Abdurrahman Sagir

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

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. (HEPATOLOGY 2007.)

Treatment of chronic hepatitis delta with pegylated interferon‐α2b

Abstract: Background/Aims: Chronic hepatitis D is difficult to treat. The present pilot study investigated the efficacy and tolerability of pegylated (PEG)‐interferon (IFN)‐α2b in chronic hepatitis D.

Lipodystrophy Syndrome and Self-Assessment of Well-Being and Physical Appearance in HIV-Positive Patients

The lipodystrophy syndrome (LDS) is a growing problem in human immunodeficiency virus (HIV)-positive patients treated with highly active antiretroviral therapy (HAART). It is characterized by alterations of body composition and metabolic abnormalities. The goal of the study was to investigate attitudes toward health condition, well-being, and individual appearance in relation to LDS. Outpatients between July and October 2000 in an HIV-specialized unit at the University Hospital of Düsseldorf, Germany, underwent clinical evaluation and received a standardized written questionnaire. Of 389 patients eligible for analysis, 313 patients returned completed questionnaires (response rate, 80.5%). LDS was observed in 37.7%; the predominant manifestation was lipoatrophy of the face (32.9%). Individuals with and without LDS did not differ significantly in their attitude to the quality of their health condition and the amount of disturbance of their well-being by HIV infection. Participants with LDS felt recognizable as HIV-positive by physical appearance in 30.1%, compared to 18.3% in patients without LDS (p = 0.027). This difference became more pronounced after adjustment for gender, age, stage of disease, CD4 cell count, and duration of HAART (odds ratio, 2.04, 95%-confidence interval [CI] 1.09-3.84). In conclusion, LDS does not seem to disturb the general attitude toward health condition and well-being. However, patients presenting with lipodystrophy are about twice as likely to feel recognizable as HIV-positive by their physical appearance. LDS may thus be perceived as a characteristic mark of being HIV-positive by affected persons. A stigmatizing effect and social disadvantages may be the consequences.

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.

Successful treatment of hepatitis B virus associated polyarteritis nodosa with a combination of prednisolone, α-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.

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 non‐endemic, 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 (1990–2009) were evaluated. Thirty‐nine patients had persistently normal transaminases, 86 patients had ALT with 1–2 × ULN (upper limit of normal) and 128 patients had ALT >2 × 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. J. Med. Virol. 83:968–973, 2011.

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‐α (PEG‐IFN‐α) 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‐α or PEG‐IFN‐α and ribavirin] in patients who relapsed or failed in prior therapy.

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.

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.

WIRELESS CAPSULE ENDOSCOPY FOR THE DETECTION OF SMALL BOWEL DISEASES IN HIV-1-INFECTED PATIENTS

Background and AimsIn 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® Video Capsule System (Given Imaging, Yoqneam, Israel) in these patients.MethodsAfter 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/μl, gastrointestinal symptoms present. Group B: HIV-positive, CD4 < 200/μl, without gastrointestinal symptoms (n = 19 Group) C: healthy volunteers (n = 11).ResultsIn group A there was a total of 30 pathological findings, 15 of which with 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 the ligament of Treitz (p = 0.001). All capsules were recovered without complications after 12 to 96 h from the stool.ConclusionWireless capsule endoscopy of the small intestine should be considered for HIV-infected patients with marked immunosuppression and gastrointestinal symptoms.