Belinda Mössner

Antibacterial properties of EMLA and lidocaine in wound tissue biopsies for culturing.

If a tissue biopsy from a chronic wound is sampled for culture, the antibacterial properties of local anesthetics may pose a problem in producing false‐negative results. The purpose of this study was to investigate the effects of EMLA® (AstraZeneca) and lidocaine on common wound pathogenic bacteria. An in vitro study of a total of 25 clinical isolates and ATCC reference strains of Staphylococcus aureus (including methicillin‐resistant S. aureus), Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes was conducted. The isolates were exposed to the local anesthetic drugs (and some of their contents separately) at 35°C over a 24‐hour period and time–kill curves were recorded. No culture media were used and saline was used for controls. EMLA® was found to have a rapid acting and powerful antibacterial effect and should not be used before culturing tissue samples. Lidocaine 1% was found not to inhibit the bacterial strains when exposure time was held below 2 hours. We conclude that culturing tissue from a wound biopsy is safe within 2 hours when a pure, preservative‐free lidocaine 1% solution is used.

Liver stiffness measurement among patients with chronic hepatitis B and C: results from a 5-year prospective study.

Liver stiffness measurement (LSM) is widely used to evaluate liver fibrosis, but longitudinal studies are rare. The current study was aimed to monitor LSM during follow-up, and to evaluate the association of LSM data with mortality and liver-related outcomes. We included all patients with chronic viral hepatitis and valid LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and clinical outcome was obtained from medical records and national registers. The study included 845 patients: 597 (71%) with hepatitis C virus (HCV), 235 (28%) with hepatitis B virus (HBV) and 13 (2%) with dual infection. The initial LSM distribution (<7/7–9.9/10–16.9/≥17 kPa) was 58%/16%/14%/12%. Among patients with initial LSM values of 7–9.9 kPa, 60% of HCV patients and 83% of HBV patients showed LSM values of <7 kPa at the latest follow-up. Progression rates (defined as >20% and >2 kPa increase, with one measure >7 kPa) were 3.4/100 person years (PY) for HCV and 1.5/100 PY for HBV infected patients. Patients with LSM values of ≥17 kPa had the same liver-related complication incidence as patients with biopsy-proven cirrhosis (11.1 versus 12.1/100 PY). Thirteen liver-related deaths occurred among HCV patients (0.6/100 PY), but none among HBV patients. Among patients who died of liver-related causes, all but one had baseline LSM values of ≥17 kPa. Overall, patients with LSM values <17 kPa were not associated with adverse outcomes. In contrast, LSM values ≥17 kPa were associated with significant risk of liver-related problems. The results of the current study suggest that clinical decisions should not be taken based on a single LSM measurement.

Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

AIM To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti-HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA. RESULTS Samples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.

Decline in hepatitis B infection observed after 11 years of regional vaccination among Danish drug users

The aims of this study were to determine the current prevalence of viral hepatitis and HIV among drug users, and to compare this prevalence with previous findings in the same geographical region. Cross‐sectional surveys of drug users attending treatment centers on the island of Funen with approximately 500,000 inhabitants were administered in 1996 and 2007. The 2007 prevalence estimates were: anti‐HBc 50.2%, HBsAg 0.9%, anti‐HCV 66.8%, HCV‐RNA 40%, and anti‐HIV 1.1%. The corresponding 1996 prevalence values were: anti‐HBc 70% (P < 0.0001), HBsAg 9.8% (P < 0.0001), anti‐HCV 82.8% (P < 0.0001), HCV‐RNA 56.3% (P = 0.002), and anti‐HIV 1% (P = 1). The 2007 prevalence of viral hepatitis decreased due to the increasing proportion of non‐injectors. Among injectors, the prevalence remained unchanged except for a significant decrease in HBsAg. The 2007 prevalence of ongoing HBV infection among infected (HBsAg/anti‐HBc proportion) was the lowest that to our knowledge has been reported among drug‐users. Vaccination coverage among susceptible persons tested in 2007 was 24%, compared to 0.7% in 1996. Therefore, despite an unchanged prevalence of anti‐HBc among injecting drug users, a highly significant drop in HBsAg prevalence was seen during the last decade. This observation may be linked causally to an increase in hepatitis B vaccination of the susceptible population. Our findings suggest that even incomplete vaccination, without persistent protective anti‐HBs levels, may induce an immune memory sufficient to prevent chronic infection upon transmission. J. Med. Virol. 82:1635–1639, 2010. 2010 Wiley‐Liss, Inc.

Microfibrillar-Associated Protein 4: A Potential Biomarker for Screening for Liver Fibrosis in a Mixed Patient Cohort

Background and Aims A method for assessment of liver fibrosis and cirrhosis without the need for a liver biopsy is desirable. Microfibrillar-associated protein 4 (MFAP4) is a suggested biomarker for identification of high-risk patients with severe fibrosis stages. This study aimed to examine associations between plasma MFAP4 (pMFAP4) and transient elastography or chronic hepatitis C virus infection in drug users and in a mixed patient cohort with increased risk of liver disease. Moreover, the study aimed to identify comorbidities that significantly influence pMFAP4. Methods pMFAP4 was measured in samples from 351 drug users attending treatment centres and from 248 acutely hospitalized medical patients with mixed diagnoses. Linear and logistic multivariate regression analyses were performed and nonparametric receiver operating characteristic-curves for cirrhosis were used to estimate cut-off points for pMFAP4. Univariate and subgroup analyses were performed using non-parametric methods. Results pMFAP4 increased significantly with liver fibrosis score. pMFAP4 was significantly associated with chronic viral infection in the drug users and with transient elastography in both cohorts. In the mixed patient cohort, pMFAP4 was significantly increased among patients with a previous diagnosis of liver disease or congestive heart failure compared to patients with other diagnoses. Conclusions pMFAP4 has the potential to be used as an outreach-screening tool for liver fibrosis in drug users and in mixed medical patients. pMFAP4 level is positively associated with transient elastography, but additional studies are warranted to validate the possible use of pMFAP4 in larger cohorts and in combination with transient elastography.

Liver stiffness and 30-day mortality in a cohort of patients admitted to hospital

Eur J Clin Invest 2011

Feasibility of transient elastography versus real-time two-dimensional shear wave elastography in difficult-to-scan patients

Abstract Background and aims: Transient elastography (TE) is hampered in some patients by failures and unreliable results. We hypothesized that real time two-dimensional shear wave elastography (2D-SWE), the FibroScan XL probe, and repeated TE exams, could be used to obtain reliable liver stiffness measurements in patients with an invalid TE examination. Methods: We reviewed 1975 patients with 5764 TE exams performed between 2007 and 2014, to identify failures and unreliable exams. Fifty-four patients with an invalid TE at their latest appointment entered a comparative feasibility study of TE vs. 2D-SWE. Results: The initial TE exam was successful in 93% (1835/1975) of patients. Success rate increased from 89% to 96% when the XL probe became available (OR: 1.07, 95% CI 1.06–1.09). Likewise, re-examining those with a failed or unreliable TE led to a reliable TE in 96% of patients. Combining availability of the XL probe with TE re-examination resulted in a 99.5% success rate on a per-patient level. When comparing the feasibility of TE vs. 2D-SWE, 96% (52/54) of patients obtained a reliable TE, while 2D-SWE was reliable in 63% (34/54, p < 0.001). The odds of a successful 2D-SWE exam decreased with higher skin-capsule distance (OR = 0.77, 95% CI 0.67–0.98). Conclusions: Transient elastography can be accomplished in nearly all patients by use of the FibroScan XL probe and repeated examinations. In difficult-to-scan patients, the feasibility of TE is superior to 2D-SWE.

Four weeks of ledipasvir/sofosbuvir and ribavirin with or without pegylated interferon for chronic hepatitis C in non-cirrhotic people who inject drugs. A randomized trial

Citation for pulished version (APA): Øvrehus, A. L. H., Krarup, H., Birkemose, I., Holm, D. K., Mössner, B., Ernst, A., & Christensen, P. B. (2018). Four weeks of ledipasvir/sofosbuvir and ribavirin with or without pegylated interferon for chronic hepatitis C in non-cirrhotic people who inject drugs. A randomized trial. Journal of Hepatology, 68(4), 840-842. https://doi.org/10.1016/j.jhep.2017.11.031

Regression of cirrhosis of the liver detected by elastiometry

TO THE EDITOR: We report the case of a 30-year-old immigrant from Vietnam who was referred to our department with chronic hepatitis B in April 2005. The infection had been diagnosed 6 years earlier as part of an antenatal screening program. The patient had probably been infected with hepatitis B virus (HBV) at birth. At presentation the patient had no clinical signs of cirrhosis: alanine aminotransferase (ALAT) was 703 IU/l (16 times upper limit of normal (ULN)), international normalized ratio (INR) 1,1, albumin 41 g/l, HBsAg positive, HBeAg positive, HBV genotype B and HBV DNA 2.5 10 IU/l. Alpha fetoprotein was 41 KIU/l (ULN 14) and an ultrasound of the abdomen was normal. During the following 6 months ALAT remained elevated (200 400 IU/l). A 45-mm liver biopsy showed cirrhosis with multiple nodules of regeneration (Figure 1). The patient was started on treatment with lamivudine (100 mg q.i.d.) in November 2005. Within one month of treatment ALATand alpha-fetoprotein were normalized but after 12 months HBV-DNA was still detectable and adefovir (10 mg q.i.d.) was added to the treatment. In June 2007, after 20 months of treatment, transient elastography was performed and showed a liver stiffness of 4.4 kPa compatible with a liver without significant fibrosis. The patient had seroconverted to anti-HBe positivity, but remained HBV-DNA positive below the limit of quantification. A 50-mm liver biopsy after 24 months of treatment showed loss of regeneration nodules, and only one single thin connective tissue septum was found in the biopsy (Figure 2). To the best of our knowledge this is the first time that transient elastography has been used to identify complete regression of cirrhosis subsequently confirmed by liver biopsy. We did not have an elastiometry measurement at the time of the first biopsy, but the histology of the first liver biopsy leaves no doubt that the patient had cirrhosis. A possibility is sampling error of the second biopsy so that this was taken within a macro-nodule of a cirrhotic liver. However, the biopsy had a length 3 times longer than what is considered the minimal requirement for a diagnostic liver biopsy, and the histology was in agreement with the findings by elastiometry, which have a very high sensitivity for detecting cirrhosis.

Depressive symptoms are frequent among drug users, but not associated with hepatitis C infection.

Abstract Aim: To compare the prevalence and severity of depressive symptoms among drug users with and without hepatitis C virus (HCV) infection. Methods: This was a cross-sectional survey study carried out at the 2 major drug treatment centres on the island of Funen, Denmark. Participants were drug users presenting to the 2 treatment centres. Individuals with chronic hepatitis B virus or HIV infection were excluded. Participants completed the Major Depression Inventory (MDI) questionnaire when presenting at the centres. Patients with MDI scores indicating severe depression (total MDI score ≥ 35) were referred for treatment evaluation. Hepatitis C status was classified by the presence of anti-HCV as a marker of HCV exposure and HCV-RNA as a marker of ongoing infection. Results: Two hundred and sixty-eight patients were included, of whom 235 (88%) had complete serological testing; 100 (43%, 95% confidence interval (CI) 36–49%) had chronic hepatitis C. The median MDI score was 22 (interquartile range 12–33); 32% (95% CI 26–39%) had a score compatible with depression and 14% (95% CI 10–19%) were rated as severe depression. Depression was not associated with hepatitis C (HCV-infected 29%, non-infected 35%; p = 0.25). Forty-one percent (11/27) of the evaluated participants started antidepressant treatment. Conclusions: Our study demonstrated a high prevalence of depressive symptoms among drug users, but this was not more frequent among HCV-infected patients. The high overall prevalence of depression underlines the relevance of screening for depression in patients who are drug users.