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The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all-type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age- and sex-matched population-based comparison cohort of individuals (n = 26 070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all-type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all-type cancer among HBV-infected patients was 1.1 (95% confidence intervals (CI) 0.9-1.3). The IRR of HCC was 17.4 (CI 5.5-54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3-2.5) and 1.2 (CI 0.4-3.6), respectively. HBV-infected patients had a 10-year risk of 0.24% (Cl 0.12-0.44) for HCC, whereas the comparison cohort had a 10-year risk of 0.03% (Cl 0.02-0.07) for HCC. The risk of all-type cancer, NHL and PC was not higher in the HBV-infected cohort compared to non-HBV infected. We found a 17-fold higher risk of HCC for HBV-infected individuals.

BACKGROUND: Risk of cancer is increased in HIV-infection. To our knowledge, no previous study has examined the association between socioeconomic position and risk and prognosis of cancer among HIV-infected individuals.METHODS: Population-based cohort-study including HIV-infected individuals diagnosed in Denmark 1995-2011 (without intravenous drug abuse or hepatitis C infection) (n=3,205), and a comparison cohort from the background population individually-matched by age, gender and country of birth (n=22,435). Educational level (low or high) and cancer events were identified in Danish national registers. Cumulative incidences, Incidence rate ratio (IRR) and survival using Kaplan-Meier methods were estimated.RESULTS: Low educational level was associated with increased risk of cancer among HIV-infected individuals compared to the comparison cohort: all cancers (Adjusted-IRRs: 1.4(95% CI;1.1-1.7) vs. 1.1(95% CI;0.9-1.2)), tobacco- & alcohol-related cancers (2.1(95% CI;1.3-3.4) vs. 1.3(95% CI;1.1-1.6)), and other cancers (1.7(95% CI;1.1-2.8) vs. 0.9(95% CI;0.7-1.0)). No association with educational level was found for Infection-related or Ill-defined cancers. 1-year-survival was not associated with educational level, but 5-year-survival following Infection-related and Ill-defined cancers was lower among HIV-infected individuals with low educational level.CONCLUSION: Education is associated with risk and prognosis of some cancers in HIV-infection, and this association diverges from what is observed in the background population.

To estimate annual employment rates and disability retirement rates (DRRs) among HIV-infected individuals and population controls during the period 1996-2011.A population-based cohort study including all HIV-infected individuals born in Denmark and not reporting intravenous (i.v.) drug abuse as a route of HIV infection or diagnosed with hepatitis C infection (n = 2799) and 22,369 individually matched persons from the background population. Study inclusion was 1 January 1996 or HIV diagnosis, which ever came last.Data on employment status and disability pension were extracted from Danish national registries. Employment rate and DRR were estimated in each calendar year after study inclusion for the cohorts included before 1996 (pre-1996), 1996-1999 and 2000-2011.Employment rate in the year of study inclusion increased from 54.8% [95% confidence interval (CI) 50.5-59.6] in the pre-1996 cohort to 74.6% (66.9-83.2) and 77.4% (72.8-82.2) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 85.9-87.2% in the comparison cohorts. Five years from study inclusion, employment rates were 56.1 (51.4-61.1), 66.2 (58.7-74.6) and 70.9% (65.0-77.3) in the pre-1996, 1996-1999 and 2000-2011 cohorts, respectively, compared with 82.5-85.6% in the comparison cohorts. Five years from study inclusion, DRRs were 32.3 (28.9-36.3) in the pre-1996 cohort and decreased to 17.8 (14.1-22.4) and 11.6% (9.4-14.4) in the 1996-1999 and 2000-2011 cohorts, respectively, compared with 5.1-7.2% in the comparison cohorts.After the introduction of HAART, employment rates have increased profoundly among HIV-infected individuals, but have remained lower than in the background population. During the same period, DRRs decreased among HIV-infected individuals, but still remained higher than in the background population.

OBJECTIVE: To estimate association between educational attainment and risk of HIV diagnosis, response to HAART, all-cause, and cause-specific mortality in Denmark in 1998-2009.DESIGN: Prospective, population-based cohort study including 1277 incident HIV-infected patients without hepatitis C virus or intravenous drug abuse identified in the Danish HIV Cohort Study and 5108 individually matched population controls.METHODS: Data on educational attainment, categorized as low, medium, or high, were identified in The Danish Attainment Register. Logistic and Poisson regression were used to estimate odds ratios (ORs) and mortality rate ratios (MRRs).RESULTS: OR of HIV diagnosis was 1.7 (95% confidence interval, CI 1.3-2.3) among heterosexual individuals with low educational attainments, but no associations between educational attainment and time to HAART initiation, CD4 cell count, or viral suppression were identified. All-cause MRRs were 1.8 (95% CI 1.0-3.2) and 1.8 (1.1-2.8) for HIV-infected patients and population controls with low educational attainment compared with medium and high educational attainment. MRRs for smoking and alcohol-related deaths were 3.6 (95% CI 1.5-8.9) for HIV-infected patients and 2.0 (95% CI 1.2-3.4) for population controls with low educational attainment compared with medium and high educational attainment.CONCLUSION: With free and equal access to healthcare, low educational attainment might increase risk of HIV infection among heterosexual individuals, but was not associated with late/very late presentation of HIV, time to HAART initiation, or HAART response. However, low educational attainment substantially increased lifestyle-related mortality, which indicates that increased mortality in HIV-infected patients with low educational attainments stems from risk factors unrelated to HIV.

Lars Haukali Omland,1 Merete Osler,2 Peter Jepsen,3,4 Henrik Krarup,5 Nina Weis,6 Peer Brehm Christensen,7 Casper Roed,1 Henrik Toft Sørensen,3 Niels Obel1 On behalf of the DANVIR Cohort Study1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Research Center for Prevention and Health, Copenhagen University Hospital, Glostrup Hospital, Glostrup, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark; 5Department of Clinical Biochemistry, Aalborg Hospital, Aalborg, Denmark; 6Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark; 7Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground and aims: It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection.Methods: From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs) for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs) for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender.Results: When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26) for disability pensioners and 2.24 (95% CI: 1.83–2.72) for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01) for low income persons and 1.19 (95% CI: 1.02–1.40) for medium income persons. The OR was 1.35 (95% CI: 1.20–1.52) for low education (no more than basic schooling). When compared to employed patients, MRRs were 1.71 (95% CI: 1.22–2.40) for unemployed patients and 2.24 (95% CI: 1.63–3.08) for disability pensioners. When compared to high income patients, MRRs were 1.47 (95% CI: 1.05–2.05) for medium income patients and 1.64 (95% CI: 1.13–2.34) for low income patients. Educational status was not associated with mortality.Conclusion: Low SES was associated with an increased risk of HCV infection and with poor prognosis in HCV infected patients.Keywords: survival, socioeconomic status, risk factor, prognosis

Importance While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. Objective To determine the risk of cutaneous cancer in HSCT recipients and compare it with the risk in renal transplant recipients (RTRs) and individuals who have not received any transplant. Design, Setting, and Participants A nationwide population-based cohort study from the Danish National Hospital Register including 3302 patients who underwent HSCT (1007 allogeneic, 2295 autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up in specialized hospital departments in Denmark (total population 5.7 million). Main Outcomes and Measures Primary outcomes were time to first appearance of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or malignant melanoma (MM) and comparative risk estimates of cutaneous cancers in HSCT recipients and RTRs. The hypothesis was tested during data collection. Results Allogeneic HSCT recipients had an increased risk of BCC, SCC, and MM, with respective HRs of 3.1 (95% CI, 1.9-5.2), 18.3 (95% CI, 4.1-81.8), and 5.5 (95% CI, 1.7-17.7) compared with the background population. Compared with RTRs, allogeneic HSCT recipients had a 3-fold higher risk of MM. The risk of BCC after allogeneic HSCT was seen only in patients conditioned with total-body irradiation (HR, 3.9 [95% CI, 2.6-6.8]). The risk of BCC was similar for allogeneic HSCT recipients and RTRs, while the risk of SCC was highest for RTRs. Autologous HSCT recipients had no increased risk of skin cancer. Conclusions and Relevance Allogeneic HSCT recipients have an increased risk of BCC, SCC, and MM. Total-body irradiation was a major determinant for BCC. Our findings indicate the relevance of dermatologic follow-up in HSCT recipients.

Background A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. Methods Patients with a diagnosis of chronic hepatitis C were identified from four national registers: a laboratory register, the Hospital Discharge Register, a clinical database of chronic viral hepatitis and the Register of Communicable Diseases. The total population diagnosed with hepatitis C was estimated by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. Results A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population diagnosed with the disease was 9,166 persons (95% C.I. interval 8,973 – 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the Danish population over 15years of age. The prevalence was highest among persons 40–49years old (0.39%) and males (0.28%). It was estimated that 40% of the diagnosed patients lived in the capital region, and 33.5% had attended specialised healthcare. It was estimated that 46% of hepatitis C patients had not been diagnosed and the total population with chronic hepatitis C in Denmark was 16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the population over 15years of age. Conclusions The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care.

Background We determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to (HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse and compared the mortality to that of the general population. Methodology/Principal Findings In a Danish nationwide, population-based cohort study, we used population based registries to identify (1) all Danish HIV-infected patients who started HAART in the period 1 January 1998–1 July 2009, and (2) a comparison cohort of individuals matched on date of birth and gender (N = 2,267 and 9,068, respectively). Study inclusion began 1 year after start of HAART. Patients were categorised hierarchically in four groups according to the three risk factors, which were identified before study inclusion. The main outcome measure was probability of survival from age 25 to 65 years. The probability of survival from age 25 to age 65 was substantially lower in HIV patients [0.48 (95% confidence interval (CI) 0.42–0.55)] compared to the comparison cohort [0.88 (0.86 to 0.90)]. However, in HIV patients with no risk factors (N = 871) the probability of survival was equivalent to that of the general population [0.86 (95% CI 0.77–0.92)]. In contrast, the probability of survival was 0.58 in patients with HIV risk factors (N = 704), 0.30 in patients with comorbidities (N = 479), and 0.03 in patients with drug or alcohol abuse (N = 313). Conclusions The increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful HAART is almost identical to that of the non–HIV-infected population.

Objective The risk of neurocognitive disorders in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART) is controversial. We aimed to compare the incidence and impact on mortality of severe neurocognitive disorders (SNCDs) in HIV-infected patients with that of the background population. Methods The method used was a nationwide, population-based cohort study using Danish registries. We calculated incidence rates, incidence rate ratios, mortality rate ratios, and Kaplan-Meier tables to estimate the incidence of and survival after SNCD in HIV-infected patients, compared with a general population control cohort matched by age and sex. Results We observed 32 cases of SNCDs among 4452 HIV-infected patients and 120 cases of SNCDs among 62 328 population control subjects. The overall risk of SNCD among HIV-infected patients was 1.0 case per 1000 person-years (PYR), compared with 0.23 cases per 1000 PYR for population control subjects but became 0.35 cases/1000 PYR after 2004, compared with 0.27 cases/1000 PYR in population control subjects. The absence of HAART and a low CD4 lymphocyte count increased the risk of SNCD. The mortality among HIV-infected patients with SNCD was higher than that among population controls with SNCD (median survival, 4.3 years vs 9.7 years [P = .02]). Conclusion HIV-infected patients have an increased risk of SNCD, but the risk is low and has, in recent years, become comparable to that seen in the background population. In contrast, the mortality remains high among HIV-infected patients diagnosed with SNCD.

Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied. The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% (95% confidence interval (CI): 0.8 - 1.3%) and 0.1% (95% CI: 0.1 - 0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91 -fold increased risk of HCC (95% CI: 28.99 - 136.52), a 29.97 -fold increased risk of NHL during the first year of follow-up (95% CI: 6.08 - 147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36 - 4.41). Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67 - 13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.

BackgroundThe increased mortality in HCV-infected individuals partly stems from viral damage to the liver and partly from risk-taking behaviours. We examined mortality in patients who cleared their HCV-infection, comparing it to that of the general population. We also addressed the question whether prognosis differed according to age, substance abuse (alcohol abuse and injection drug use) and comorbidity.Methodology/principal findingsPatients with cleared HCV-infection were categorized into one of 8 groups according to age (20-39 years or 40-69 years) and patient characteristics (no substance abuse/no comorbidity; substance abuse/no comorbidity; no substance abuse/comorbidity; and substance abuse/comorbidity). For each patient, 4 age- and gender-matched individuals without substance abuse or comorbidity were selected from the general population, comprising a total of 8 comparison cohorts. We analyzed 10-year survival and used stratified Cox Regression analysis to compute mortality rate ratios (MRRs), comparing mortality between the 8 patient groups and the comparison cohorts, adjusting for personal income. Among patients without substance abuse or comorbidity, those aged 40-69 years had the same mortality as the comparison cohort (10-year survival: 95% (95% confidence interval [CI]: 93%-97%), MRR: 1.3 (95% CI: 0.8-2.3)), whereas those aged 20-39 years had higher mortality than the comparison cohort (10-year survival: 93% versus 99%, MRR: 5.7 (95% CI: 2.3-14.0). For both age categories, substance abuse and comorbidity decreased survival and increased MRRs. Patients aged 40-69 years with substance abuse and comorbidity suffered from substantial mortality (MRR: 12.5 (95% CI: 5.1-30.6)).ConclusionsMortality in patients aged 40-69 years with cleared HCV-infection is comparable to individuals without HCV, provided they have no substance abuse or comorbidity. Any substance abuse and/or comorbidity not captured in the registries used for our study could explain the increased mortality in patients aged 20-39 years without documented substance abuse or comorbidity.

According to the Swiss Federal Commission for HIV/AIDS, HIV-infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.A Danish, population-based nationwide cohort study of HIV-infected patients with VL51 HIV-1 RNA copies/mL for more than 6 months was carried out for the study period 2000-2008. The observation time was calculated from 6 months after the first VL51 copies/mL to the last measurement of VL or the first VL50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL51 copies/mL to the subsequent VL if it was1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5-0.8%] of the overall observation time the patients had VL1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5-11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0-0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low.

Background Previous studies have indicated an increased risk of myocardial infarction (MI) in HIV infected individuals especially after start of highly active antiretroviral therapy (HAART). It is however controversial whether the increased risk of atherosclerotic disease is exclusively associated with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk of MI in parents of HIV-infected individuals. Methods From the Danish HIV Cohort Study and the Danish Civil Registration System we identified the parents of all HIV-infected patients born in Denmark after 1952 in whom a Danish born mother was identifiable. For each HIV patient, 4 matched population controls and their parents were identified. Cumulative incidence functions were constructed to illustrate time to first MI of the parents as registered in the Danish National Hospital Registry. Incidence rate ratios (IRR) were estimated by Cox's regression analyses. Due to the confidential type of the analysed data the study was approved by the Danish Data Protection Agency. Results 2,269 mothers and 2,022 fathers of HIV patients as well as 9,076 mothers and 8,460 fathers of control subjects were identified. We observed an increased risk of MI in mothers of HIV patients (adjusted IRR, 1.31; 95% CI: 1.08-1.60). The strongest association was seen in case the offspring was infected heterosexually (adjusted IRR, 1.59; 95% CI: 1.07-2.35) or by IV drug abuse (IVD) (adjusted IRR, 1.63; 95% CI: 1.02-2.60). In fathers of HIV patients the risk of MI was only increased if the offspring was infected by IVD (adjusted IRR, 1.42; 95% CI: 1.01-2.00). Conclusion Mothers of HIV-infected patients have an increased risk of MI. We presume that this stems from family related life style risk factors, some of which may also influence the risk of MI in HIV-infected patients.

BACKGROUND & AIMS:: The long-term mortality of patients infected with hepatitis C virus (HCV) is not known; few studies have controlled for potential confounders, investigated how mortality changes with age at diagnosis and length of follow-up evaluation, provided absolute risk estimates of death, or analyzed specific causes of death. METHODS:: By using a Danish population, we compared mortality of a cohort of 10,991 HCV-infected patients with that of an age- and sex-matched cohort. By using regression analysis, we adjusted for municipality of residence, history of psychiatric illness, comorbidities, alcohol and drug abuse, and income. We analyzed causes of death and effects of HCV with age and length of follow-up evaluation. RESULTS:: HCV-infected patients had lower income levels and more comorbidities, psychiatric illnesses, and substance and alcohol abuse than the comparison cohort. The 10-year survival rate decreased from 84.1% among HCV-infected patients aged 20 to 29 years to 21.1% among those age 70 years or older. The increased risk of death among HCV-infected patients was more pronounced in the first year of follow-up evaluation than in subsequent years and in the unadjusted than in the adjusted analysis. Starting in the second year of follow-up evaluation, HCV-infected patients aged 20 to 29 years had an 18.2-fold increased risk of death, whereas those that were 70 years or older had a 1.6-fold increased risk. Most deaths among younger patients were from unnatural causes and most deaths among patients 70 years or older were from non-liver-related natural causes. CONCLUSIONS:: HCV infection is associated with increased mortality; younger patients (age, 20-29 y) have an increased risk of unnatural death.

Objectives To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. Design Population-based, nation-wide prospective cohort study in Denmark (the Danish HIV Cohort Study). Methods A total of 4578 HIV-infected patients were followed from 1 January 1997 or date of HIV diagnosis. We calculated mortality rates stratified on IDU. One-, 5- and 10-year survival probabilities were estimated by Kaplan–Meier methods, and Cox regression analyses were used to estimate mortality rate ratios (MRR). Results Of the patients, 484 (10.6%) were categorized as IDUs and 4094 (89.4%) as non-IDUs. IDUs were more likely to be women, Caucasian, hepatitis C virus (HCV) co-infected and younger at baseline; 753 patients died during observation (206 IDUs and 547 non-IDUs). The estimated 10-year survival probabilities were 53.2% [95% confidence interval (CI): 48.1–58.3] in the IDU group and 82.1% (95% CI: 80.7–83.6) in the non-IDU group. IDU as route of HIV infection more than tripled the mortality in HIV-infected patients (MRR: 3.2; 95% CI: 2.7–3.8). Adjusting for potential confounders did not change this estimate substantially. The risk of HIV-related death was not increased in IDUs compared to non-IDUs (MRR 1.1; 95% CI 0.7–1.7). Conclusions Although Denmark's health care system is tax paid and antiretroviral therapy is provided free of charge, HIV-infected IDUs still suffer from substantially increased mortality in the HAART era. The increased risk of death seems to be non-HIV-related and is due probably to the well-known risk factors associated with intravenous drug abuse.

Udgivelsesdato: 2010 Summary. Acute hepatitis C virus (HCV) infection may lead to chronic HCV-infection with detectable HCV RNA or to spontaneous clearance with no HCV RNA, but detectable HCV antibodies. It is unknown whether HCV RNA status is associated with mortality in HIV-infected injection drug users (IDUs). We conducted a nationwide population-based cohort study to examine the impact of HCV RNA status on overall and cause-specific mortality in HIV-infected IDUs. We computed cumulative mortality and used Cox Regression to estimate mortality rate ratios (MRR). We identified 392 HIV-infected patients of whom 284 (72%) had chronic HCV-infection (HCV RNA positive patients) and 108 (28%) had cleared the HCV-infection (HCV RNA negative patients). During 1286 person-years of observation (PYR), 157 persons died (MR = 122/1000 PYR, 95% CI: 104-143). The estimated 5-year probabilities of survival were 0.58 (95% CI: 0.51-0.65) in the chronically HCV-infected and 0.52 (95% CI: 0.40-0.63) in the cleared HCV group. Chronic HCV-infection was not associated with overall mortality: MRR 0.85, 95% CI: 0.59-1.21. In HIV-infected Danish IDUs, chronic HCV-infection is not associated with increased mortality compared to patients who have cleared the infection.

Udgivelsesdato: 2010-Mar-29 BACKGROUND & AIMS: It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies. METHODS: This nationwide cohort study focused on Danish patients with at least one HCV RNA measurement available after testing positive for HCV antibodies between 1996 and 2005. To capture long-term prognosis, eligible patients needed to be alive 1year after HCV RNA assessment. We estimated mortality rate ratios (MRRs) using Cox regression (for overall mortality) and subdistribution hazard ratios (SDHRs) for cause-specific mortality, controlling for gender, age, comorbidity, calendar period, alcohol abuse, injection drug use and income. RESULTS: Of the 6292 patients under study, 63% had chronic HCV-infection and 37% had cleared the virus. Five-year survival was 86% (95% confidence interval (CI): 84-87%) in the chronic HCV group and 92% (95% CI: 91-94%) in the cleared HCV group. Chronic HCV-infection was associated with higher overall mortality (MRR: 1.55, 95% CI: 1.28-1.86) and liver-related death (SDHR: 2.42, 95% CI: 1.51-3.88). Chronic HCV-infection greatly increased the risk of death from primary liver cancer (SDHR: 16.47, 95% CI: 2.24-121.00). CONCLUSIONS: Patients with chronic HCV-infection are at higher risk of death than patients who cleared the infection. The substantial association found between chronic HCV-infection and death from primary liver cancer supports early initiation of antiviral treatment in chronically HCV-infected patients.

Objective To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV). Methods From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient, four control HCV patients without HIV were matched on age, gender and year of HCV diagnosis. Data on comorbidity, drug abuse, alcoholism and date of death were extracted from two healthcare databases. We constructed Kaplan–Meier curves and used Cox regression analyses to estimate mortality rate ratios (MRRs), controlling for comorbidity. Results We identified 483 HCV–HIV co-infected and 1932 HCV mono-infected patients, yielding 2192 and 9894 person-years of observation with 129 and 271 deaths, respectively. The 5-year probability of survival was 0.74 [95% confidence interval (CI) 0.69–0.80] for HCV–HIV co-infected patients and 0.87 (95% CI 0.85–0.89) for HCV mono-infected patients. Co-infection was associated with substantially increased mortality (MRR 2.1, 95% CI 1.7–2.6). However, prior to the first observed decrease in CD4 counts to below 300 cells/μL, HIV infection did not increase mortality in HCV-infected patients (MRR 0.9, 95% CI 0.5–1.50). Conclusions HIV infection has a substantial impact on mortality among HCV-infected individuals, mainly because of HIV-induced immunodeficiency.

Udgivelsesdato: 2008-Nov-13 Background. @nbsp; Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. Methods. @nbsp; Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. Results. @nbsp; Among 4649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/muL at diagnosis of PML was significantly associated with reduced mortality. Conclusions. @nbsp; The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.

Udgivelsesdato: 2008-Sep-17

Background Hospital-based discharge registries are used increasingly for longitudinal epidemiological studies of HIV. We examined completeness of registration of HIV infections and of chronic hepatitis B (HBV) and hepatitis C (HCV) coinfections in the Danish National Hospital Registry (DNHR) covering all Danish hospitals. Methods The Danish HIV Cohort Study (DHCS) encompasses all HIV-infected patients treated in Danish HIV clinics since 1 January 1995. All 2,033 Danish patients in DHCS diagnosed with HIV-1 during the 10-year period from 1 January 1995 to 31 December 2004 were included in the current analysis. We used the DHCS as a reference to examine the completeness of HIV and of HBV and HCV coinfections recorded in DNHR. Cox regression analysis was used to estimate hazard ratios of time to diagnosis of HIV in DNHR compared to DHCS. Results Of the 2,033 HIV patients in DHCS, a total of 2,006 (99%) were registered with HIV in DNHR. Of these, 1,888 (93%) were registered in DNHR within one year of their first positive HIV test. A CD4 < 200 cells/μl, a viral load >= 100,000 copies/ml and being diagnosed after 1 January 2000, were associated with earlier registration in DNHR, both in crude and adjusted analyses. Thirty (23%) HIV patients registered with chronic HBV (n = 129) in DHCS and 126 (48%) of HIV patients with HCV (n = 264) in DHCS were registered with these diagnoses in the DNHR. Further 17 and 8 patients were registered with HBV and HCV respectively in DNHR, but not in DHCS. The positive predictive values of being registered with HBV and HCV in DHCS were thereby estimated to 0.88 and 0.97 and in DNHR to 0.32 and 0.54. Conclusion The study demonstrates that secondary data from national hospital databases may be reliable for identification of patients diagnosed with HIV infection. However, the predictive value of co-morbidity data may be low.

Background The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. Methods This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. Results HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1–2.1], liver-related mortality (MRR 4.0; 95% CI 1.6–9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0–3.0). The presence of HBeAg did not influence patients' response to HAART. Conclusions In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.

Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV-2 in the CSF was determined by polymerase chain reaction (PCR), and patients were diagnosed as encephalitis or meningitis according to predefined clinical criteria by retrospective data information from consecutive clinical journals. The annual crude incidence rate of HSV-2 CNS disease was 0.26 per 100,000. 43 (88%) had meningitis of whom 8 (19%) had recurring lymphocytic meningitis. Six patients (12%) had encephalitis. 11 of 49 patients (22%) had sequelae recorded during follow-up. None died as a result of HSV-2 CNS disease. Thus, the clinical presentation of HSV-2 infection of the CNS is mainly meningitis but encephalitis does occur and neurological sequelae are common. Recurring lymphocytic meningitis is associated with reactivation of HSV-2 and the condition might be underdiagnosed. Udgivelsesdato: 2008-null

The DHCS is a cohort of all HIV-infected individuals seen in one of the eight Danish HIV centres after 31 December 1994. Here we update the 2009 cohort profile emphasizing the development of the cohort. Every 12-24 months, DHCS is linked with the Danish Civil Registration System (CRS) in order to extract an age- and sex-matched comparison cohort from the general population, as well as cohorts of family members of the HIV-infected patients and of the comparison cohort. The combined cohort is linked with CRS, the Danish Cancer Registry, the Danish National Hospital Registry, the Danish Registry of Causes of Death, the Danish National Prescription Registry, the Attainment Register and the Integrated Database for Labour Market Research to get information on vital status, migration, cancer, hospital contacts, causes of death, dispensed prescriptions, education and employment. Using this design, rates of a range of outcomes have been compared between HIV-infected patients and the comparison cohort, as well as between families of these two cohorts in order to disaggregate the effects of HIV infection and familial/environmental factors. Data can be shared with foreign institutions following approval from the Danish Data Protection Agency. Potential collaborators can contact the study director, Niels Obel (e-mail: niels.obel@regionh.dk).

Importance To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. Objective To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. Design, Setting, and Participants Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. Main Outcomes and Measures Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. Results By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H influenzae meningitis patients were economically self-sufficient and 1.5% (3.7% vs 2.3%; 95% CI, −0.2% to 3.2%), 8.7% (10.0% vs 1.3%; 95% CI, 5.0%-12.4%), and 3.7% (6.2% vs 2.5%; 95% CI, 1.6%-5.8%) more received disability pension compared with individuals from the comparison cohort. Conclusions and Relevance In a Danish population, bacterial meningitis in childhood was associated with lower educational achievement and economic self-sufficiency in adult life. This association may apply particularly to pneumococcal and H influenzae meningitis, whereas for meningococcal meningitis the lower educational achievement may be family-related.

BACKGROUND: With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. METHODS: A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972-2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death. FINDINGS: A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09-2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31-60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34-5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. CONCLUSION: Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.

Background In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented. Methodology/Principal Findings We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12–1.45), adjusted MRR, 1.21 (95% CI, 1.06–1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82–7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92–1.48). Conclusions Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases.