Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. METHODS: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage [F], lobular inflammation grade [LI], hepatocyte ballooning grade [HB], and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. RESULTS: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0-1 vs. F3: 0.22 [95% CI: 0.12-0.42]), LI1 versus LI2-3 (0.42 [0.19-0.97]), and HB1 versus HB2 (0.20 [0.08-0.50]). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0-1: 0.12 [0.05-0.25]), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. CONCLUSIONS: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.

FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is unknown. We aimed to assess the association between FAST score and histological endpoints. Methods: We conducted a post-hoc analysis using data from a prior randomised, double-blind, placebo-controlled, phase 2b trial at 143 sites across 16 countries. Patients (aged 18-75 years) with biopsy-confirmed NASH, fibrosis stage 1-3, and a Non-alcoholic fatty liver disease Activity Score (NAS) ≥4 were enrolled between January 2017 and September 2018, and randomly assigned to receive once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg or placebo for 72 weeks. A subgroup analysis of patients with FAST score and histological data in the pooled semaglutide treatment and placebo arms at baseline and week 72 was performed. The original trial is registered at ClinicalTrials.gov, NCT02970942. Findings: A total of 122 patients were included in this post-hoc analysis (93 received semaglutide and 29 received placebo). FAST score reduction was associated with achieving the primary endpoint of NASH resolution without worsening of fibrosis in the pooled semaglutide group (area under the receiver operating curve 0.69; 95% confidence interval [CI] 0.58, 0.81). Mean FAST score reduction from baseline to week 72 was greatest in patients who met the primary endpoint vs those who did not in both the semaglutide (-0.40 [95% CI -0.84, 0.04] vs -0.22 [95% CI -0.74, 0.30] points; p = 0.002) and placebo groups (-0.25 [95% CI -0.72, 0.23] vs 0.00 [95% CI -0.50, 0.50] points; p = 0.047). Similarly, mean reductions in FAST score at week 72 were greater in those with NAS improvement vs those without in the semaglutide and placebo groups (≥1 point, -0.36 [95% CI -0.82, 0.11] vs -0.08 [95% CI -0.53, 0.38] points [p < 0.001] and -0.25 [95% CI -0.64, 0.14] vs -0.06 [95% CI -0.40, 0.53] points [p = 0.001]; ≥2 points, -0.40 [95% CI -0.86, 0.06] vs -0.14 [95% CI -0.56, 0.28] points [p < 0.001] and -0.29 [95% CI -0.67, 0.09] vs -0.05 [95% CI -0.40, 0.50] points; [p < 0.001]). A FAST score reduction of more than 0.22 points after semaglutide treatment was associated with meeting the primary endpoint (sensitivity 78%; specificity 60%; positive likelihood ratio 1.26; negative likelihood ratio 0.25; odds ratio 4.93). Interpretation: The potential of the FAST score as a non-invasive monitoring tool to identify histological changes following treatment requires further evaluation and validation. Funding: Novo Nordisk A/S.

Improved health-related quality of life with semaglutide in people with non-alcoholic steatohepatitis: A randomised trial.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) can adversely affect health-related quality of life (HRQoL). AIMS: This double-blind, placebo-controlled, phase 2 trial aimed to report the effects of the glucagon-like peptide-1 receptor agonist, semaglutide, on HRQoL in patients with NASH as a secondary endpoint. METHODS: Adults with biopsy-proven NASH and stage 1-3 fibrosis were randomised (3:3:3:1:1:1) to once-daily subcutaneous semaglutide 0.1, 0.2 or 0.4 mg, or placebo, for 72 weeks. Patients were invited to complete the Short Form-36 version 2.0 questionnaire at weeks 0, 28, 52 and 72. RESULTS: Between January 2017 and September 2018, 320 patients were enrolled. At 72 weeks, semaglutide was associated with significant improvements in physical component summary (PCS) score (estimated treatment difference [ETD] 4.26; 95% confidence interval [CI]: 1.96-6.55; p = 0.0003); bodily pain (ETD 5.07; 95% CI: 2.15-7.99; p = 0.0007); physical functioning (ETD 3.51; 95% CI: 1.16-5.86; p = 0.0034); role limitations due to physical health problems (ETD 2.80; 95% CI: 0.28-5.33; p = 0.0294); social functioning (ETD 3.16; 95% CI: 0.53-5.78; p = 0.0183) and vitality (ETD 4.47; 95% CI: 1.63-7.32; p = 0.0021). There was no significant difference in the mental component summary score (ETD 1.02; 95% CI: -1.59 to 3.62; p = 0.4441). After 72 weeks, improvements in PCS scores were significantly greater in patients (pooled semaglutide and placebo) with NASH resolution than without (p = 0.014). CONCLUSIONS: Treatment with semaglutide is associated with improvements in the physical components of HRQoL in patients with biopsy-proven NASH and fibrosis compared with placebo. CLINICALTRIALS: gov: NCT02970942.

Association of birth by cesarean section with academic performance and intelligence in youth: A cohort study.

INTRODUCTION: It is suggested that birth by elective cesarean section (CS) reduces the risk of birth-related infant mortality and injury. Other studies suggest an increased risk of somatic immune-related diseases among children born by CS such as asthma, type 1 diabetes, and inflammatory bowel disease. The WHO Statement on Cesarean Section Rates 2015 described an increase in CS globally. The statement concluded that the effects of CS on social and psychological outcomes remain unclear and that more research is needed to fully understand the effects of CS, including effects on cognition and intelligence in the child. Therefore, we aimed to investigate the association between delivery by CS (elective and acute) and school performance and intelligence in youth. MATERIAL AND METHODS: This cohort study included all Danish live-born children in 1978-2000. We retrieved data regarding pregnancies, births, parents, school grades, and intelligence of the children from Danish registers and performed multiple imputations to avoid discarding data. The final cohort after exclusion comprised 1 408 230 children. Associations between CS and school graduation, grades, conscription attendance, and conscription intelligence scores were analyzed using univariate and multivariate logistic and linear regressions. RESULTS: Adjusted odds ratio with 95% CI of graduating from lower (LSE) and upper (USE) secondary education and of attending conscription were significantly lower in the CS group: LSE graduation: 0.87 (0.84-0.89), USE graduation: 0.93 (0.92-0.94), attending conscription: 0.95 (0.93-0.98). The CS group had significantly lower grade point averages (GPA) in LSE with adjusted differences in mean total GPA of -0.090 (-0.10 to -0.007), and mean core subject GPA of -0.098 (-0.11 to -0.08), in USE with total GPA difference of -0.091 (-0.11 to -0.075) and lower mean intelligence scores of -0.36 (-0.46 to -0.27) in adjusted linear models. A sub-analysis revealed lower chances of graduating LSE and USE when born by acute rather than elective CS. CONCLUSIONS: Chances of LSE and USE graduation and of attending conscription were significantly lower for children born by CS. However, even significant differences in mean GPAs and intelligence scores were very small, so performances when graduating school and attending conscription were comparable regardless of delivery mode.

Association of Apgar score at 5 minutes with academic performance and intelligence in youth: A cohort study.

INTRODUCTION: The Apgar score is routinely given at childbirth worldwide. A low Apgar score at 5 minutes is a strong predictor for neonatal death. Scores below 7 have been associated with higher risks of later neurologic disability. Few studies have assessed the association between Apgar score and school performance and intelligence. The existing literature points towards a possible association between Apgar score and later cognitive function, but the contradictions call for further investigation to fully understand the potential association. This study aimed to examine the possible association between Apgar score at 5 minutes and academic performance and intelligence in youth. MATERIAL AND METHODS: The study is a cohort study. The cohort consists of all Danish liveborn children in 1978-2000 (n = 1 450 681). Data regarding pregnancies, births, parents, school grades, and intelligence of the children were retrieved from different Danish registers. Multiple imputations were performed to avoid discarding data. After exclusion, the final cohort consisted of 1 005 241 children. Associations between Apgar score at 5 minutes and school graduation, grades and attendance, and intelligence scores from conscription were analyzed using univariate and multivariate logistic and linear regressions. RESULTS: No association was found between Apgar score and graduating primary school. Adjusted odds ratio (aOR) of graduating upper secondary education and attending conscription were significantly lower for children with scores below 7 compared with 7-10: graduating upper secondary education: Apgar 0-3: aOR 0.79 (95% CI 0.67-0.93), Apgar 4-6: aOR 0.86 (95% CI 0.81-0.93), attending conscription: Apgar 0-3: aOR 0.73 (95% CI 0.59-0.91), Apgar 4-6: aOR 0.73 (95% CI 0.66-0.80). The Apgar 4-6 group had significantly lower total mean primary school grade average: -0.13 (95% CI -0.21 to -0.054) and lower mean intelligence scores at conscription: -0.57 (95% CI -1.09 to -0.058). All other differences remained insignificant. CONCLUSIONS: Performances when graduating school and attending conscription were overall equal regardless of Apgar score at 5 minutes. Chances of graduating primary school were the same irrespective of the score, but chances of graduating upper secondary education and attending conscription were significantly lower with scores below 7. The results suggest that children with scores below 7 may fail to appear at upper secondary education and conscription, but if they do, they perform equally to anyone else.

Risk of hypoglycaemia with insulin degludec versus insulin glargine U300 in insulin-treated patients with type 2 diabetes: the randomised, head-to-head CONCLUDE trial.

AIMS/HYPOTHESIS: A head-to-head randomised trial was conducted to evaluate hypoglycaemia safety with insulin degludec 200 U/ml (degludec U200) and insulin glargine 300 U/ml (glargine U300) in individuals with type 2 diabetes treated with basal insulin. METHODS: This randomised (1:1), open-label, treat-to-target, multinational trial included individuals with type 2 diabetes, aged ≥18 years with HbA1c ≤80 mmol/mol (9.5%) and BMI ≤45 kg/m2. Participants were previously treated with basal insulin with or without oral glucose-lowering drugs (excluding insulin secretagogues) and had to fulfil at least one predefined criterion for hypoglycaemia risk. Both degludec U200 and glargine U300 were similarly titrated to a fasting blood glucose target of 4.0-5.0 mmol/l. Endpoints were assessed during a 36 week maintenance period and a total treatment period up to 88 weeks. There were three hypoglycaemia endpoints: (1) overall symptomatic hypoglycaemia (either severe, an event requiring third-party assistance, or confirmed by blood glucose [<3.1 mmol/l] with symptoms); (2) nocturnal symptomatic hypoglycaemia (severe or confirmed by blood glucose with symptoms, between 00:01 and 05:59 h); and (3) severe hypoglycaemia. The primary endpoint was the number of overall symptomatic hypoglycaemic events in the maintenance period. Secondary hypoglycaemia endpoints included the number of nocturnal symptomatic events and number of severe hypoglycaemic events during the maintenance period. RESULTS: Of the 1609 randomised participants, 733 of 805 (91.1%) in the degludec U200 arm and 734 of 804 (91.3%) in the glargine U300 arm completed the trial (87.3% and 87.8% completed on treatment, respectively). Baseline characteristics were comparable between the two treatment arms. For the primary endpoint, the rate of overall symptomatic hypoglycaemia was not significantly lower with degludec U200 vs glargine U300 (rate ratio [RR] 0.88 [95% CI 0.73, 1.06]). As there was no significant difference between treatments for the primary endpoint, the confirmatory testing procedure for superiority was stopped. The pre-specified confirmatory secondary hypoglycaemia endpoints were analysed using pre-specified statistical models but were now considered exploratory. These endpoints showed a lower rate of nocturnal symptomatic hypoglycaemia (RR 0.63 [95% CI 0.48, 0.84]) and severe hypoglycaemia (RR 0.20 [95% CI 0.07, 0.57]) with degludec U200 vs glargine U300. CONCLUSIONS/INTERPRETATION: There was no significant difference in the rate of overall symptomatic hypoglycaemia with degludec U200 vs glargine U300 in the maintenance period. The rates of nocturnal symptomatic and severe hypoglycaemia were nominally significantly lower with degludec U200 during the maintenance period compared with glargine U300. TRIAL REGISTRATION: ClinicalTrials.gov NCT03078478 FUNDING: This trial was funded by Novo Nordisk (Bagsvaerd, Denmark).

Persistence of cervical high-risk human papillomavirus in women living with HIV in Denmark - the SHADE.

BACKGROUND: Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark. METHODS: From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011-2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL. RESULTS: Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 < 350 cells/µL predicted genotype-specific hrHPV persistence (adjusted OR 4.36 (95%CI: 1.18-16.04)) and ≥ HSIL was predicted by prior AIDS (adjusted OR 8.55 (95% CI 1.21-60.28)). CONCLUSIONS: This prospective cohort study of well-treated WLWH in Denmark found a high rate of persistent hrHPV infections with predominantly non-16/18 hrHPV genotypes. CD4 count < 350 cells/µL predicted hrHPV persistence, while prior AIDS predicted ≥HSIL.

Bedside vital parameters that indicate early deterioration.

PURPOSE: The purpose of this paper is to determine associations between initially recorded deviations in individual bedside vital parameters that contribute to total Modified Early Warning Score (MEWS) levels 2 or 3 and further clinical deterioration (MEWS level=4). DESIGN/METHODOLOGY/APPROACH: This was a prospective study in which 27,504 vital parameter values, corresponding to a total MEWS level⩾2, belonging to 1,315 adult medical and surgical inpatient patients admitted to a 90-bed study setting at a university hospital, were subjected to binary logistic and COX regression analyses to determine associations between vital parameter values initially corresponding to total MEWS levels 2 or 3 and later deterioration to total MEWS level ⩾4, and to evaluate corresponding time intervals. FINDINGS: Respiratory rate, heart rate and patient age were significantly ( p=0.012, p<0.001 and p=0.028, respectively) associated with further deterioration from a total MEWS level 2, and the heart rate also ( p=0.009) from a total MEWS level 3. Within 24 h from the initially recorded total MEWS levels 2 or 3, 8 and 17 percent of patients, respectively, deteriorated to a total MEWS level=4. Patients initially scoring MEWS 2 had a 27 percent 30-day mortality rate if they later scored MEWS level=4, and 8.7 percent if they did not. PRACTICAL IMPLICATIONS: It is important to observe all patients closely, but especially elderly patients, if total MEWS levels 2 or 3 are tachypnoea and/or tachycardia related. ORIGINALITY/VALUE: Findings might contribute to patient safety by facilitating appropriate clinical and organizational decisions on adequate time spans for early warning scoring in general ward patients.

Soluble urokinase plasminogen activator receptor is linearly associated with dietary quality and predicts mortality.

Chronic inflammation is associated with disease risk and mortality in the general population. Soluble urokinase plasminogen activator receptor (suPAR) is a stable marker of chronic inflammation, and a higher serum-concentration of suPAR is found in individuals with an unhealthy lifestyle such as smoking. This article investigates the association between suPAR and dietary quality measured with the dietary quality score (DQS). The DQS is an index of the overall quality of an individual's dietary habits assessed through a self-administered FFQ. Furthermore, this article investigates the association of both suPAR and the DQS with CVD risk and mortality in the general Danish population. We analysed 5347 individuals aged 30-60 years from the Danish Inter99 study cohort. Multiple linear regression analyses showed a linear inverse association between the DQS and suPAR (P=0·0005). Cox regression analyses showed an 18 (95 % CI 9, 26) % increase in the risk of death from any cause with each 1 ng/ml increase in suPAR. We found no significant association between the DQS and the mortality (hazard ratio: 1·16, 95 % CI 0·79, 1·69). All analyses were adjusted for demographics and lifestyle factors. The association between the DQS and suPAR on the one hand and suPAR and mortality on the other supports the argument that low dietary quality may constitute a health risk through its influence on chronic inflammation. Future research should examine whether suPAR is modifiable through changes in dietary habits.

Healthy lifestyles reduce suPAR and mortality in a Danish general population study.

BACKGROUND: The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is a strong predictor of disease development and premature mortality in the general population. Unhealthy lifestyle habits such as smoking or unhealthy eating is known to elevate the suPAR level. We aimed to investigate whether change in lifestyle habits impact on the suPAR level, and whether the resultant levels are associated with mortality. RESULTS: Paired suPAR measurements from baseline- and the 5-year visit of the population-based Inter99 study were compared with the habits of diet, smoking, alcohol consumption, and physical activity. Paired suPAR measurements for 3225 individuals were analyzed by linear regression, adjusted for demographics and lifestyle habits. Compared to individuals with a healthy lifestyle, an unhealthy diet, low physical activity, and daily smoking were associated with a 5.9, 12.8, and 17.6% higher 5-year suPAR, respectively. During 6.1 years of follow-up after the 5-year visit, 1.6% of those with a low suPAR (mean 2.93 ng/ml) died compared with 3.8% of individuals with a high suPAR (mean 4.73 ng/ml), P <  0.001. In Cox regression analysis, adjusted for demographics and lifestyle, the hazard ratio for mortality per 5-year suPAR doubling was 2.03 (95% CI: 1.22-3.37). CONCLUSION: Lifestyle has a considerable impact on suPAR levels; the combination of unhealthy habits was associated with 44% higher 5-year suPAR values and the 5-year suPAR was a strong predictor of mortality. We propose suPAR as a candidate biomarker for lifestyle changes as well as the subsequent risk of mortality.

Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes.

Dissemination of information on a genetically increased risk should according to guidelines primarily be family-mediated. Incomplete and incorrect information spread has, however, been documented and implies missed possibilities for prevention. In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer. To evaluate this approach, we investigated reactions and attitudes to unsolicited letters in 708 members of families with genetic predisposition and in 1600 individuals from the general population. Support for information letters was expressed by 78% of the family members and by 82% of the general population. Regarding route of information, 90% of family members preferred a letter to no information, 66% preferred information from the hospital rather than from family members and 40% preferred to obtain information from a close family member. Our results suggest that use of unsolicited information letters from the health care system may be a feasible and highly acceptable strategy to disseminate information to families at high risk of colorectal cancer.

Patient Assessment of Family Function, Glycemic Control and Quality of Life in Adult Patients With Type 2 Diabetes and Incipient Complications.

OBJECTIVES: Family affects the perception of diabetes self-management in patients with diabetes. Family-related questionnaires have been used to assess family function, but the Brief Family Assessment Measure (Brief FAM-III) has not been used previously in a diabetes population. We aimed to determine whether the family function is associated with glycated hemoglobin levels and quality of life as potential predictors of diabetes self-management. METHODS: An exploratory study of patients with type 2 diabetes and incipient complications and their relatives using the Brief FAM-III, a self-report questionnaire comprising 3 scales assessing family function according to different perspectives: a general score, a dyadic relationship score and a self-rating score. RESULTS: We included 127 patients: 72.4% males, mean age 65.23 (SD=10.26) years; glycated hemoglobin levels, 6.9% (SD=0.9%); diabetes duration, 9.1 (SD=0.6) years; and body mass index, 30.8 (SD=0.5) kg/m2. Mean FAM-III scores for the 3 scales were 41.7 (SD=1.0), 41.5 (SD=0.9) and 38.5 (SD=1.1), respectively. Correlation coefficients were -0.06 (p=0.37), -0.09 (p=0.18) and -0.12 (p=0.06), showing no significant correlation between scales and glycated hemoglobin levels levels in the 3 perspectives before and after adjustment for confounders. Family function correlated with burden of diabetes at 0.14 (p=0.02), 0.24 (p=0.0003) and 0.16 (p=0.01), respectively, and mental health at -0.21 (p=0.0007), -0.23 (p=0.0005) and -0.25 (p<0.0001), respectively. CONCLUSION: The results of our study suggest that in patients with type 2 diabetes, family function does not predict the level of glycemic control. However, we found an association among healthy family function, low burden of diabetes and strong mental health, issues that are important for the patients' quality of life, compliance with lifestyle factors and diabetes self-management.

Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition.

Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9-5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.

The Prevalence of Human Immunodeficiency Virus Coinfection Among Patients Newly Diagnosed With Chronic Hepatitis B or C in Denmark: A Nationwide Cohort Study.

BACKGROUND: Early identification of patients with chronic viral hepatitis coinfected with human immunodeficiency virus (HIV) is essential for optimal care. The objectives of this study were to estimate the prevalence of HIV coinfection among patients newly diagnosed with chronic viral hepatitis, HIV testing prevalence, and identify factors associated with coinfection. METHODS: Patients with chronic viral hepatitis newly enrolled in The Danish Database for Hepatitis B and C between 2002 and 2015 were identified. The HIV coinfection prevalence was calculated, and risk factors associated with HIV coinfection were estimated by logistic regression. RESULTS: In total, 8490 patients were included: 3091 had chronic hepatitis B (CHB), 5305 had chronic hepatitis C (CHC), and 94 had CHB and CHC. The prevalence of HIV coinfection was 4.4% (95% confidence interval [CI], 4.0-4.9) and was higher among CHC and CHB-CHC patients than CHB patients with a prevalence of 5.3% (95% CI, 4.7-5.9), 6.4% (95% CI, 2.4-13.4), and 2.9 (95% CI, 2.3-3.5), respectively (P < .0001). The HIV testing prevalence increased from 65% to 88% between 2002 and 2014 concurrently with a decrease in the HIV coinfection prevalence from 7.8% (95% CI, 5.5-10.7) to 1.6% (95% CI, 0.7-3.2). Age 35-50 years, male sex, and sexual route of viral hepatitis transmission were associated with HIV coinfection with odds ratios of 4.42 (95% CI, 1.40-13.94), 2.21 (95% CI, 1.74-2.81), and 8.81 (95% CI, 6.30-12.33), respectively. CONCLUSIONS: The prevalence of HIV coinfection among patients with newly diagnosed chronic viral hepatitis decreased concurrently with an increase in HIV testing prevalence.

Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study.

OBJECTIVES: Soluble urokinase plasminogen activator receptor is a prognostic biomarker associated with critical illness, disease progression, and risk of mortality. We aimed to evaluate whether soluble urokinase plasminogen activator receptor adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score) in acute medical patients. DESIGN: Registry-based observational cohort study of consecutively admitted acute medical patients. SETTING: The Acute Medical Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. PATIENTS: Acute medical patients admitted between November 18, 2013, and September 30, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 17,312 included patients, admission National Early Warning Score was available for 16,244 (93.8%). During follow-up, 587 patients (3.4%) died in-hospital, 859 (5.0%) within 30 days, and 1,367 (7.9%) within 90 days. High soluble urokinase plasminogen activator receptor was significantly associated with in-hospital-, 30-day-, and 90-day mortality within all National Early Warning Score groups, in particular in patients with a low National Early Warning Score; for 30-day mortality, mortality rate ratios ranged from 3.45 (95% CI, 2.91-4.10) for patients with National Early Warning Score 0-1, to 1.86 (95% CI, 1.47-2.34) for patients with National Early Warning Score greater than or equal to 9 for every doubling in soluble urokinase plasminogen activator receptor (log2-transformed). Combining National Early Warning Score, age, and sex with soluble urokinase plasminogen activator receptor improved prediction of in-hospital-, 30-day-, and 90-day mortality, increasing the area under the curve (95% CI) for 30-day mortality from 0.86 (0.85-0.87) to 0.90 (0.89-0.91), p value of less than 0.0001, with a negative predictive value of 99.0%. CONCLUSIONS: The addition of soluble urokinase plasminogen activator receptor to National Early Warning Score significantly improved risk prediction of both low- and high-risk acute medical patients. Patients with low National Early Warning Score but elevated soluble urokinase plasminogen activator receptor had mortality risks comparable to that of patients with higher National Early Warning Score.

Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark - The SHADE cohort study.

BACKGROUND: Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers. OBJECTIVES: To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark. STUDY DESIGN: WLWH followed in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) were enrolled and examined for cervical, oral, and anal HPV infection. Logistic regression models were used to identify predictors of anal and oral HPV. RESULTS: A total of 214 of 334 WLWH had sufficient DNA for analysis at all three anatomical sites and were included in analyses. Cervical, oral, and anal high-risk (hr) HPV prevalence were 28.0%, 3.7% and 39.3%. Most frequent i) cervical, ii) oral and iii) anal hrHPV genotypes were i) hrHPV58 (8.4%), 52 (5.1%), 16 (5.1%) and 51 (5.1%); ii) 52 (1.4%) and iii) 51 (9.3%), 58 (8.9%), 16 (7.0%) and 18 (7.0%). Among present cervical, oral, and anal hrHPV genotypes, 6.7%, 12.5% and 17.9% were targeted by the 2-or 4-valent HPV vaccines, whereas 50.0%, 50.0% and 42.9% of hrHPV genotypes were covered by the 9-valent HPV vaccine. Anal HPV infection was predicted by cervical HPV infection (adjusted OR 4.47 (95%CI 2.25-8.89)). CONCLUSION: Cervical and anal HPV infection were highly prevalent in WLWH. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half of all hrHPV infections at the three anatomical sites could have been prevented by childhood/adolescent vaccination with the 9-valent HPV vaccine.

suPAR is associated with risk of future acute surgery and post-operative mortality in acutely admitted medical patients.

BACKGROUND: Acutely admitted medical patients are often fragile and in risk of future surgery. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is a predictor of readmission and mortality in the acute care setting. We aimed to investigate if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality. METHODS: A retrospective registry-based cohort study of 17,312 patients admitted to an acute medical unit in Denmark, from 18 November 2013 until 30 September 2015. The first admission with available suPAR was defined as the index admission, and patients were followed via national registries until 1 January 2016. The risk of acute surgery during the entire follow-up period as well as the 90-day post-operative mortality risk was modeled by Cox regression analyses adjusted for sex, age, C-reactive protein, and Charlson Comorbidity Index (Charlson Score). RESULTS: Acute surgery was carried out on 2404 patients (13.9%) after a median of 45 days (interquartile range 5-186) following the index admission. Patients receiving acute surgery had higher baseline suPAR compared with patients receiving elective- or no surgery (p < 0.0001). The hazard ratio (HR) for acute surgery was 1.50 (95% confidence interval (CI): 1.42-1.59) for every doubling of the suPAR level in the adjusted Cox regression analysis. Death within 90 days occurred in 439 (18.3%) patients receiving acute surgery, and the adjusted HR for post-operative mortality was 1.73 (95% CI: 1.52-1.95). DISCUSSION: Elevated levels of suPAR in acutely admitted medical patients were independently associated with increased risk of future acute surgery as well as with 90-day post-operative mortality. TRIAL REGISTRATION: This retrospective registry-based cohort study was approved by the Danish Health and Medicines authority (reference no. 3-3013-1061/1). All processing of personal data followed national guidelines, and the project was approved by the Danish Data Protection Agency (reference no. HVH-2014-018, 02767).

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response.

BACKGROUND: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. MATERIALS AND METHODS: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013. RESULTS: Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43-1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36-1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22-0.62) for HCC and 0.31 (95% CI 0.17-0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR. CONCLUSION: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.