Update – Therapie Hepatitis B und D

Zusammenfassung. Weltweit leiden 240 Millionen Menschen an einer chronischen Hepatitis-B-Infektion, und jährlich sterben Hunderttausende an den Folgen dieser Krankheit. Die Hauptübertragungswege sind ungeschützter Geschlechtsverkehr und Nadeltausch sowie die perinatale, vertikale Übertragung von der Mutter aufs Neugeborene. Die Diagnose einer Hepatitis B wird allein durch serologische Bestimmung von Antigenen und Antikörpern gestellt. Für eine HB-Screening-Untersuchung reicht die Bestimmung des HBsAg sowie der HBs- und HBc-Antikörper. Vor allem im Kindesalter erworbene Hepatitis-B-Infektionen chronifizieren sehr häufig (&gt; 90 %). Von einer chronischen Hepatitis B spricht man bei HBsAg-Persistenz von über sechs Monaten. Die chronische Hepatitis B verläuft in verschiedenen Stadien („natural history“). Die erste Phase nach der Ansteckung ist die sogenannte Immuntoleranzphase, gefolgt von der immunreaktiven Phase. Die beste Prognose haben Patienten, welche in der inaktiven Phase der chronischen Hepatitis B sind (früher: „inaktive Carrier“). Nach HBeAg-Serokonversion kann es zu einem Wiederanstieg der Transaminasen und der Viruslast kommen Diese Phase wird als HBeAg negative chronische Hepatitis B bezeichnet. Verlieren die Patienten das HBsAg, spricht man von einer okkulten Infektion. Heute existieren zwei Therapiestrategien: 48-wöchige Therapie mit subkutan appliziertem PEG-Interferon und eine perorale Langzeit-Therapie mit Nukleosid / Nukleotid-Analoga. Eine besondere Patientengruppe stellen unter anderem Schwangere und Patientinnen im gebärfähigen Alter dar, bei welchen vor allem die Übertragung aufs Neugeborene verhindert werden soll. Patienten mit chronischer oder durchgemachter Hepatitis B, welche eine immunsuppressive Therapie erhalten, sind dem Risiko einer Hepatitis B Exazerbation / Reaktivierung ausgesetzt, und in dieser Situation sollte immer eine antivirale Therapie evaluiert werden. Das Hepatitis-D-Virus tritt immer gemeinsam mit einer Hepatitis-B-Infektion auf. Die einzig mässig effektive Therapie der Hepatitis D ist eine 12-monatige PEG-Interferontherapie. Die effektivste Prophylaxe gegen Hepatitis B und D besteht in der aktiven Immunisierung mittels eines Totimpfstoffs. </jats:p

Disseminated Mycobacterium simiae and Mycobacterium avium infection causing an immune reconstitution inflammatory syndrome in a female patient with HIV infection

This case study discusses the management of a disseminated Mycobacterium simiae and Mycobacterium avium infection causing an immune reconstitution inflammatory syndrome in a 52-year-old woman with HIV infection. Disseminated M. avium infections have extensively been described in HIV patients; however, reports of infections with M. simiae are rare. Treatment of M. simiae infections is challenging due to its high rates of natural drug resistances, and thus far, no standard treatment regimen exists

Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis

Background & aims With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. Methods 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman’s correlation and AUROC analyses. Results Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman’s rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65–0.83), and 0.67(95%CI 0.56–0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. Conclusions sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4

Excellent outcome of direct antiviral treatment for chronic hepatitis C in Switzerland

BACKGROUND The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. AIMS OF THE STUDY We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. METHODS We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. RESULTS Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. CONCLUSION In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients

Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer

PURPOSE To evaluate the prognostic value of positive surgical margins (PSM) focality for the prediction of biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP) for prostate cancer. METHODS All men with clinically localized prostate cancer undergoing RARP in our tertiary referral centre between May 2005 and August 2016 were retrospectively identified. Patients with neoadjuvant therapy were excluded. Comparisons were made between cases with negative surgical margins (NSM), unifocal PSM (uPSM), and multifocal PSM (mPSM). RESULTS From a total of 973 patients available for analysis, 315 (32%) had a PSM. In these patients, 190 had uPSM and 125 had mPSM. Focality of PSM was significantly associated with tumour stage and grade, preoperative PSA, and postoperative PSA persistence (all p < 0.001), but not with nerve sparing (NS) (p = 0.15). PSA persistence was found in 120 (12%) patients, resulting in 853 patients available for survival analyses with a median follow-up of 52 months. Both uPSM and mPSM were found to be independent predictors of BCR, conferring a hazard ratio of 1.9 (95% CI 1.3-3.0; p = 0.002) and 3.4 (95% CI 2.1-5.6; p < 0.001), respectively, when compared to NSM. In subgroup analyses, PSM was particularly predictive for BCR when patients underwent unilateral or bilateral NS (p ≤ 0.003). CONCLUSIONS Based on a large case series of RARP, we found PSM focality to be an independent predictor of BCR, with a 1.9- and 3.4-fold risk increase for BCR in case of uPSM and mPSM, respectively. PSM seems to be of particular prognostic relevance when NS has been performed

DAA treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers FIB-4 and APRI

BACKGROUND Novel direct antiviral agents (DAA) targeting hepatitis C virus (HCV) have revolutionized the treatment of chronic hepatitis C infection (CHC). Rates of sustained virological response (SVR) to treatment have drastically improved since introduction of DAA. Transient Elastography (TE) is an ultrasound based, non-invasive technique to assess liver stiffness (LS). We examined the changes in TE values and fibrosis scores FIB-4 and APRI after DAA treatment of CHC. METHODS 549 patients who received a DAA based treatment for CHC were screened and 392 were included. TE values recorded prior to therapy and within 18 months after therapy were evaluated. In addition, FIB-4 and APRI scores were calculated and histological results were recorded if available. RESULTS Median TE prior to DAA treatment was 12.65 kPa (IQR 9.45 - 19.2 kPa) and decreased to 8.55 kPa (IQR 5.93 - 15.25) post-treatment. This finding is statistically significant (p < 0.001) and equals a TE regression of 32.41% after DAA treatment. Median FIB-4 and APRI values significantly decreased from 2.54 (IQR 1.65-4.43) and 1.10 (IQR 0.65-2.43) to 1.80 (IQR 1.23-2.84, p < 0.001) and 0.43 (IQR 0.3-0.79, p < 0.001), respectively. CONCLUSION Patients with SVR after DAA therapy showed significant regression of TE values. Rapid decrease of TE was in concordance with regression of validated fibrosis scores FIB-4 and APRI. It remains to be examined whether this indicates a regression of fibrosis or merely resolution of chronic liver inflammation with subsequent improvement of TE values and laboratory parameters. This article is protected by copyright. All rights reserved