Altered balance between collagen formation and degradation after successful direct-acting antiviral therapy of chronic hepatitis C.

The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers' dynamics with DAA therapy in CHC patients. Plasma PRO-C3, PRO-C4, C3M and C4M were assessed before, during and up till one year after 12-24 weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n = 14) or cirrhosis (n = 63). Liver stiffness was evaluated using transient elastography. PRO-C3, C3M and C4M levels decreased significantly (P < .00001) while PRO-C4 was unchanged (P = .20) during the study period. There was a steep decrease in the PRO-C3/C3M ratio during DAA therapy and follow-up (P < .02). The PRO-C4/C4M ratio was unchanged (P > .27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had >20% higher levels of C3M, PRO-C4 and C4M at all time points (P < .05). The collagen markers correlated with liver stiffness at baseline and follow-up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.

Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis.

Laursen TL, Sandahl TD, Kazankov K, Eriksen PL, Kristensen LH, Holmboe CH, Laursen AL, Vilstrup H, Grønbæk H. Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis. Am J Physiol Gastrointest Liver Physiol 319: G151-G156, 2020. First published June 29, 2020; doi:10.1152/ajpgi.00128.2020.-Effects of direct-acting antiviral (DAA) treatment of chronic hepatitis C (CHC) cirrhosis on metabolic liver function are unknown but important for prognosis. Ureagenesis is an essential metabolic liver function involved in whole body nitrogen homeostasis. We aimed to investigate the ureagenesis capacity before and immediately after DAA therapy and relate the findings to hepatic inflammation and structural changes. In an observational before-and-after intervention study, the ureagenesis capacity was quantified by functional hepatic nitrogen clearance (FHNC) in 9 CHC patients with cirrhosis and 10 healthy volunteers. Hepatic inflammation was evaluated by alanine aminotransferase (ALT) and the macrophage activation markers sCD163 and sMR. Structural changes were estimated as liver stiffness and by portal hypertension as the hepatic venous pressure gradient (HVPG). Before treatment, the FHNC in the patients was half of the controls [16.4 L/h (8.2-24.5) vs. 33.4 (29.2-37.6), P = 0.0004]; after successful DAA treatment, it normalized [28.4 (15.9-40.9), P = 0.008 vs. baseline]. DAA treatment normalized ALT (P < 0.0001) and decreased the elevated sCD163 from 5.6 mg/L (3.5-7.7) to 3.4 (2-0-4.8) (P < 0.001) and sMR from 0.35 mg/L (0.21-0.49) to 0.31 (0.17-0.45) (P < 0.01). Liver stiffness fell by 30% (P < 0.05) but remained over the cirrhosis threshold. HVPG was not affected (P = 0.59). DAA treatment restored the severely reduced ureagenesis capacity, along with amelioration of hepatic inflammation but without normalization of other cirrhosis characteristics. Our findings indicate that the anti-inflammatory effect of virus eradication independent of hepatic structural effects rapidly improves metabolic dysfunction. We suggest this effect to be an important early onset part of the expected clinical DAA treatment benefit.NEW & NOTEWORTHY Antiviral treatment of chronic hepatitis C restores the liver's reduced capacity to produce urea along with an improvement in liver inflammation without immediate effects on structural liver changes. The effect is suggested to be an important early onset part of the expected clinical treatment benefit.

Time-dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct-acting antiviral therapy of chronic hepatitis C.

Sofosbuvir-based direct-acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy-one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir-based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow-up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post-treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one-year follow-up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark.

OBJECTIVE: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission. MATERIALS AND METHODS: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc. RESULTS: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission. CONCLUSION: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.

The role of Fusobacterium necrophorum in pharyngotonsillitis - A review.

Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. In addition, it is also associated with peritonsillar abscess formation and otitis media in small children. Recent research has shown that F. necrophorum may be involved in pharyngotonsillitis especially in adolescent and young adults and that it may be the second most common bacterial cause of pharyngotonsillitis after Streptococcus pyogenes (Group A streptococci). Peritonsillar abscesses and Lemierre's syndrome due to F. necrophorum are also found in this age group, suggesting that they may be complications of F. necrophorum pharyngotonsillitis. In this review we present the present knowledge about the role of F. necrophorum in pharyngotonsillitis with special emphasis on the age distribution. We argue that F. necrophorum is an important pathogen involved in pharyngotonsillitis in the age group of 13-40 years of age and we urge clinical microbiology labs to set up the appropriate techniques to be able to detect F. necrophorum from throat swabs.

Arterial ischemic stroke as a complication to disseminated infection with Fusobacterium necrophorum.

Lemierre syndrome (LS) is a rare complication of oropharyngeal and odontogenic infections in otherwise healthy young individuals. It is characterized by septic internal jugular vein thrombophlebitis and disseminated metastatic abscesses. Cerebral arterial ischemic stroke is rarely seen in LS. The authors present a 14-year-old, previously healthy girl, who developed cerebral arterial infarction following acute tonsillitis and abscess formations due to Fusobacterium necrophorum.

Testing for hepatitis B virus and HIV in patients with chronic hepatitis C: screening performance and outcome.

BACKGROUND: Patients infected with hepatitis C virus (HCV) and co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at increased risk for progression of liver disease. The aim of this study was to assess HBV and HIV screening performance and outcome in HCV patients followed at a Danish university hospital and affiliated regional outpatient clinics. METHODS: HBV and HIV serology data were extracted from a quality assurance database for the assessment of screening performance in patients diagnosed with chronic HCV infection during the period 1 January 1996 to 31 December 2011. Patients with incomplete and missing serology data had complementary serology tests performed to assess the prevalence of HBV and HIV co-infection and HBV immune status. RESULTS: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32 (5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an unknown HBV serology status. Serology results consistent with resolved infection and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively. During the 16-y observation period, HBV and HIV screening coverage at HCV diagnosis increased from 23% to 92% and from 38% to 80%, respectively. CONCLUSION: Despite improvements throughout the study period, HBV and HIV serology screening remained incomplete. The majority of patients were either HBV non-immune or had an unknown HBV serology status. These findings thus call for a more proactive screening approach as well as an improved HBV vaccination strategy for patients with chronic HCV infection.

Splenic Abscess in an Adolescent due to Salmonella enterica Conservatively Treated with Ultrasound-Guided Fine-Needle Aspiration.

Background: Splenic abscesses are rare and potentially fatal. Diagnosis is often delayed due to vague symptoms, and laboratory findings are varying and often nonspecific. Ultrasound and computed tomography have a high sensitivity in detecting splenic abscesses. Splenectomy was previously considered the gold standard for treatment, but in recent years, a shift has been seen towards a more conservative approach, i.e., ultrasound-guided aspiration or drainage in combination with adequate antibiotics in selected cases. Case Report. A previously healthy adolescent complained of left-sided chest pain, pain in the left clavicular region for three weeks, and recent fever. Ultrasound and computed tomography demonstrated an intrasplenic abscess. The patient was successfully treated with two percutaneous fine-needle punctures and adequate antibiotics for six weeks. Salmonella enterica serotype Poona was grown from the aspirate. At one-year follow-up, the patient remained healthy without signs of recurrence. Conclusion: The present case report demonstrates that ultrasound-guided aspiration and subsequent treatment with antibiotics may be an effective alternative to splenectomy in patients with a splenic abscess.

[Outbreak of nephropathiaepidemica in Jutland, Denmark].

In Denmark, most cases of nephropathia epidemica (NE) occur on the island of Funen and are caused by the transmission of Puumala hantavirus to humans from the bank vole. This is a case report comprising four cases of NE occurring in close vicinity to Silkeborg, Jutland, where the disease is not usually seen. NE is characterised by increased vascular permeability, and patients present with flu-like symptoms progressing to acute kidney injury. When NE occurs in areas where it has not traditionally been endemic, awareness of the disease is important to ensure proper diagnosis.

Complete Genome Sequences of Two Isolates of Fusobacterium necrophorum subsp. funduliforme, Obtained from Blood from Patients with Lemierre's Syndrome.

Two isolates (F1260 and F1291) of Fusobacterium necrophorum subsp. funduliforme were recovered from blood from patients with Lemierre's syndrome. Here, we report the complete genome sequences of these two isolates. The genomes of F1260 and F1291 comprise one chromosome with lengths of 2.29 and 2.14 Mb, respectively.

[Compression is important in erysipelas treatment].

Erysipelas is a common skin infection involving the lymphatic vessels, which induces an oedema. This has a tendency of persisting after infection is treated. The lymphatic system plays an important role in the immune system, and the impaired lymph drainage leads to a state of local immune deficiency. This is essential to the pathogenesis of recurrent erysipelas, as each episode of erysipelas further damages the lymphatic system and increases the risk of a new infection. This vicious circle makes it important to treat both erysipelas and oedema appropriately to reduce recurrence and morbidity.

Rotavirus is frequent among adults hospitalised for acute gastroenteritis.

INTRODUCTION: Rotavirus infection is the most common aetiology of acute gastroenteritis (AGE) among young children. In adults, diagnostics focus mainly on bacterial causes, though recent studies suggest that rotavirus is a frequent agent. The aim of this study was to examine the proportion of rotavirus in adults hospitalised with AGE and to identify possible predictors. METHODS: During a 24-month period from 1 May 2010 adults (> 15 years) with AGE admitted to one of four hospitals in the Central Denmark Region were examined for rotavirus with VIKIA Rota-Adeno rapid test in addition to routine culture for bacterial pathogens. RESULTS: A total of 265 adult patients were included. 9.4% tested positive for rotavirus. Enteropathogenic bacteria were found in 24.5% of the cases. In the majority of cases (62.3%), no pathogen was found. Overall, rotavirus was the second-most frequent pathogen, exceeded only by Campylobacter spp. Immunosuppression and a C-reactive protein (CRP) below 50 mg/l (0-8 mg/l) were associated with rotavirus. The seasonality of rotavirus differed markedly from that of bacterial gastroenteritis. CONCLUSION: Rotavirus is the second-most frequently identified pathogen in adults hospitalised with AGE. Close contact to children or travel activity does not predict rotavirus gastroenteritis, but immunosuppression and a CRP below 50 mg/l do. The seasonality of rotavirus differs from that of bacterial gastroenteritis, making rotavirus the most frequently identified cause of AGE in adults admitted to hospital in the colder months. FUNDING: The trial was funded by an unrestricted grant from Sanofi Pasteur MSD. TRIAL REGISTRATION: not relevant.

Recurrent Invasive Pneumococcal Disease Serotype 12F in a Vaccinated Splenectomized Patient.

This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded that she had responded sufficiently to vaccination. Still, she had a fulminate recurrent infection with PPV23 serotype 12F. We investigated the anti-pneumococcal IgG test, and it turned out that it is based on the geometric mean value of only 12 of the serotypes included in PPV23; 12F is none of them. The reason is that there are no titer cut-offs available for 11 of the PPV23 serotypes, including 12F, neither nationally nor internationally. Yet, this is not specified in the answer to the clinicians. This case illustrates the need for titer cut-offs for the remaining pneumococcal serotypes in available vaccines, in order to get a more accurate estimation of the vaccination coverage for the individual patient. Therefore, more research on this area is warranted, along with a discussion of whether the laboratory answers to the clinicians should be more detailed.

Fusobacterium necrophorum findings in Denmark from 2010 to 2014 using data from the Danish microbiology database.

Fusobacterium necrophorum findings in Denmark and estimation of the incidence of F. necrophorum bacteraemia was described using data from the nationwide Danish microbiology database (MiBa). All microbiological reports on any Fusobacterium species in Denmark were extracted for a period of 5 years from 2010 to 2014 from MiBa and from the local department of clinical microbiology. The overall incidence of F. necrophorum bacteraemia from 2010 to 2014 was 2.8 cases per million/year vs 9.4 in the age group 15-24 years. F. necrophorum was rare in blood cultures from children and middle-aged patients and then raised again. However, 48 of 232 cases of Fusobacterium bacteraemia were not identified to species level, so the incidences of F. necrophorum bacteraemia may be underestimated in our study. F. necrophorum was found in throat swabs in the age group between 13 and 40 years and in otitis media in children below 2 years in those departments which performed anaerobic culture. The incidence of F. necrophorum bacteraemia found was comparable to earlier reported figures for Lemierre's syndrome. Fusobacterium bacteraemia should always be identified to species level.

[Intervertebral discitis in children].

Intervertebral discitis is a rare disorder which is easily missed. It presents with non-specific symptoms such as irritability, abdominal pain, decreased appetite and limping. The infection parameters can be normal, and blood cultures are often negative. The pathogenesis is not established but infectious, and inflammatory aetiologies have been suggested. Diagnostic golden standard is magnetic resonance imaging. The treatment is immobilization, anti-inflammatory drugs and often antibiotics. Early treatment is important to reduce the risk of complications such as nerve damage and spine fusion.

Patients' answers to simple questions about treatment satisfaction and adherence and depression are associated with failure of HAART: a cross-sectional survey.

Psychosocial and behavioral factors have been shown to be associated with adherence to highly active antiretroviral therapy (HAART) and treatment effectiveness. These factors have often been identified in selected populations through complex or time-consuming questionnaires. In this study we aimed at asking all the patients of a large population-based cohort receiving HAART a few short, explicit, and direct questions about these factors, and to examine the associations between their answers and prevalent treatment failure. All patients receiving HAART in western Denmark and central Copenhagen were offered participation. Participants answered a short, self-administered, anonymous questionnaire assessing psychosocial and behavioral factors and treatment adherence. Findings were linked with data on demographics, disease history, and treatment effect. Treatment failure was defined as two consecutive measurements of HIV-RNA above 400 copies per milliliter taken at least 14 days apart. Prevalence odds ratios were estimated by logistic regression. We found that a total of 887 of 1126 patients returned a completed questionnaire (response rate 79%). The overall rate of treatment failure in participants was 20%. Adjusted odds ratio estimates for treatment failure were 2.3 (confidence interval [CI] 1.3-4.3) for patients who stated poor treatment satisfaction, 2.1 (CI 1.2-3.7) for patients not fully disagreeing that they were depressed, and 2.8 (CI 1.5-5.4) for patients who stated to have been nonadherent within the preceding 4 days. Because of the cross-sectional nature of the study, causality could not be determined. These questions, however, may be relevant screening tools in clinical practice and in follow-up studies.

[Intestinal tuberculosis--a rare differential diagnosis of Crohn's disease in an ethnic Danish woman]. / Intestinal tuberkulose, en sjælden differentialdiagnose til Crohns sygdom hos en etnisk dansker.

We report a case of intestinal tuberculosis in a 42-year-old Danish woman with stomach pain, weight loss and diarrhoea for months suspective of Crohn's disease. She underwent hysterectomy where white, small nodules were found on the small intestine. Biopsies showed non-necrotizing granulomatous inflammation. Gastroscopy and colonoscopy were normal. Capsule endoscopy revealed small intestine ulcers and a stenosis. A CT scan of the abdomen confirmed stenosis and inflammation of terminal ileum. QuantiFERON-TB Gold Test was positive and Mycobacterium tuberculosis was detected in faeces cultures.

[Pseudo-Meig's syndrome: a rare complication to uterine fibroma]. / Pseudo-Meigs' syndrom: en sjaelden komplikation til et uterint fibrom.

Pseudo-Meigs syndrome is a rare condition where a benign and non-ovarian pelvic tumour, pleural effusion and ascites are coexisting, and where removal of the tumour cures the patient. We present a patient with pseudo-Meigs syndrome originating from a leiomyoma of the uterus associated with elevated cancer antigen 125 and inflammatory parameters. Our patient also had pericardial effusion, which has only been reported once before in the literature. All her symptoms disappeared when the uterine fibroma was removed. Pseudo-Meig's syndrome has to be kept in mind in these patients.

Fusobacterium necrophorum- detection and identification on a selective agar.

Within the last decade, Fusobacterium necrophorum subsp. funduliforme has been considered a clinically important pathogen causing pharyngitis especially in adolescents and young adults. F. necrophorum pharyngitis can progress into Lemierre's syndrome, which is a severe and life-threatening infection. However, throat swabs are not cultured anaerobically in the routine and even if cultured anaerobically, it can be difficult to identify F. necrophorum from the normal flora of the throat. F. necrophorum is therefore often overlooked as the cause of pharyngitis. In our laboratory, a F. necrophorum selective agar has been developed containing vancomycin and nalidixin, which inhibit the growth of most Gram-positive and many Gram-negative bacteria, respectively. ß-haemolysis of horse blood can be detected, which further facilitates the detection and identification of F. necrophorum. The F. necrophorum selective agar was evaluated against a quantitative real-time polymerase chain reaction assay and shown to have a significantly higher sensitivity for detecting F. necrophorum than the anaerobic agar commonly used in Denmark. Furthermore, the F. necrophorum selective agar does not require experienced laboratory technicians, require fewer subcultures, is probably less expensive and is faster to perform than other culture methods.