Peer Brehm Christensen

Adenocarcinoma of the Esophagus and Barrett's Esophagus: A Population-Based Study

Objective: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barretts esophagus, making them potential candidates for endoscopic surveillance. Methods: Rates of esophageal and gastric cancers were collected from the Danish Cancer registry for the period 1970–1991. The registry was used to identify all cases of esophageal adenocarcinoma in the period 1987–1992. Medical records were retrieved and details concerning previous diagnosis of reflux disease and Barretts esophagus were recorded. Results: The age- and gender-adjusted incidence of esophageal adenocarcinoma increased eightfold, from 0.3/105/yr in 1970 to 2.3/105/yr in 1990. This increase could not be explained by changes in classification or diagnostic routines. Medical data were retrieved for 524 of the 578 cases of esophageal adenocarcinoma reported during the period 1987–1992. A history of reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524 patients. A total of 119 patients (23%) had previously been investigated for dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of Barretts esophagus was found in only 1.3% of the cancer patients. Conclusions: The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a 20-yr period, and this increase is not explained by changes in classification or diagnostic routines. More than 98% of esophageal adenocarcinomas were found in patients who could not have entered endoscopic surveillance, as Barretts esophagus had not been diagnosed before the cancer diagnosis. Endoscopic surveillance to detect dysplasia may be an option for the individual patient with Barretts esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population.

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Time Trend of the Prevalence of Hepatitis E Antibodies among Farmers and Blood Donors: A Potential Zoonosis in Denmark

BACKGROUND Antibody to hepatitis E virus (anti-HEV) is prevalent in Western countries, where clinical hepatitis E is rarely reported. The aim of this study was to determine the prevalence of anti-HEV among Danish blood donors and Danish farmers. In addition, we compared the prevalence among 2 sets of serum samples obtained from blood donors 20 years apart. METHODS Samples from 291 Danish farmers and 169 blood donors that were collected in 1983 and samples from 461 blood donors that were collected in 2003 were tested for anti-HEV. Relevant information on HEV exposure was collected by self-administered questionnaire. RESULTS Anti-HEV testing was performed on samples after 20 years of storage at -20 degrees C. The prevalence of anti-HEV was 50.4% among farmers and 32.9% among donors in 1983 and 20.6% among donors in 2003 (P < .05). Presence of anti-HEV was significantly correlated with increasing age in all 3 groups (P < .05). Among donors who had serum samples obtained in 2003, age, contact with horses, and the presence of antibody to hepatitis A virus were associated with the presence of anti-HEV in multivariate analysis. Among farmers, only age was independently associated with the presence of anti-HEV. CONCLUSION Anti-HEV was highly prevalent among Danes but has decreased in prevalence over the past 50 years. Our study supports the hypothesis that HEV infection in Denmark may be an asymptomatic zoonotic infection.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Prevalence and incidence of bloodborne viral infections among Danish prisoners

In order to determine the prevalence and incidence of bloodborne viral infections among prisoners, we conducted a prospective study in a Danish medium security prison for males. The prisoners were offered an interview and blood test for hepatitis and human immunodeficiency virus HIV at inclusion as well as at release from prison or end of study. Of 403 prisoners available 325 (79%) participated in the initial survey and for 142 (44%) a follow-up test was available. 43% (140/325) of the participants were injecting drug users (IDUs) of whom 64% were positive for hepatitis B (HBV) and 87% for hepatitis C (HCV) markers. No cases of HIV or human T lymphotropic virus (HTLV) were found. 32% of all prisoners could transmit HBV and/or HCV by blood contact. 70% of IDUs had shared injecting equipment, and 60% had injected inside prison. Only 2% of IDUs were vaccinated against HBV. Duration of injecting drug use, numbers of imprisonments, and injecting in prison were independently and positively associated with the presence of HBV antibodies among IDUs by logistic regression analysis. The HBV incidence was 16/100 PY (95% CI: 2–56/100 PY) and the HCV incidence 25/100 PY (1–140) among injecting drug users (IDUs). We conclude that IDUs in prison have an incidence of hepatitis B and C 100 times higher than reported in the general Danish population. They should be vaccinated against hepatitis B and new initiatives to stop sharing of injecting equipment in and outside prison is urgently needed.

Impact of Hepatitis C Virus Coinfection on Response to Highly Active Antiretroviral Therapy and Outcome in HIV-Infected Individuals: A Nationwide Cohort Study

BACKGROUND Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among Danish patients with HIV-1 infection. METHODS This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR results [443 patients [16%]]), HCV negative (consistent negative HCV serological test results [2183 patients [80%]]) and HCV-U (never tested for HCV [108 patients [4%]]). The study end points were viral load, CD4+ cell count, and mortality. RESULTS Compared with the HCV-negative group, overall mortality was significantly higher in the HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9-3.0), as was liver disease-related mortality (mortality rate ratio, 16; 95% CI, 7.2-33). Furthermore, patients in the HCV-positive group had a higher risk of dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count. CONCLUSIONS HIV-HCV-coinfected patients are compromised in their response to highly active antiretroviral therapy. Overall mortality, as well as mortality from liver-related and acquired immunodeficiency syndrome-related causes, is significantly increased in this patient group.

Mortality in patients with chronic and cleared hepatitis C viral infection: A nationwide cohort study

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.

Impact of hepatitis B virus co‐infection on response to highly active antiretroviral treatment and outcome in HIV‐infected individuals: a nationwide cohort study

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.

Mortality among Danish drug users released from prison

To determine the mortality of drug users after release from prison in Denmark, a cohort of drug users was identified from two national registers during 1996‐2001: the drug treatment register (T) and the register of viral hepatitis (H). Incarcerations were extracted from the national penal register, vital status from the civil register, and causes of death from the death certificate register and the police register of drug‐related deaths. We identified 15,885 drug users (T: 15,735, H: 896), 62% of the estimated drug‐using population in Denmark. There were 1000 observed deaths, of which 51% were classified as overdose deaths. Mortality in the treatment cohort was 2.4/100 person years (py) (95% C.I. 2.2‐2.5/100 py) compared to the general population expectation of 0.2/100 py. Within the first 2 weeks after release from prison, 26 deaths were observed among 6019 released drug users corresponding to 13/100 py (95% CI 8‐19/100 py). Overdose deaths accounted for 24/26 deaths (92%) in the first two weeks compared to 121/179 (68%) hereafter (p <0.001). We conclude that drug users released from prison are at high risk of overdose death. We suggest that methadone treatment should be evaluated as a way to decrease mortality after release from prison.

Outreach screening of drug users for cirrhosis with transient elastography

AIMS Transient elastography (TE) is a non-invasive sensitive tool for diagnosing cirrhosis in hospital-based cohorts. This study aimed to evaluate TE as a screening tool for cirrhosis among drug users. DESIGN Cross-sectional study. SETTING All treatment centres in the county of Funen, Denmark. PARTICIPANTS Drug users attending treatment centres during the presence of the study team. MEASUREMENTS Liver stiffness measurements (LSM) by transient elastography using the Fibroscan device; blood tests for viral hepatitis, HIV infection and hyaluronic acid (HA) levels; and routine liver tests. Individuals with LSM ≥ 8 kPa were referred to the hospital for treatment evaluation. Individuals with LSM ≥ 12 kPa were recommended a liver biopsy. FINDINGS Among 175 drug users negative for hepatitis C, 13% had LSM = 8-11.9 kPa and 4% had LSM ≥ 12 kPa; elevated LSM was associated with a body mass index (BMI) > 30. Among 128 drug users with chronic hepatitis C, 19.5% had LSM = 8-11.9 kPa and 21.1% had LSM ≥ 12 kPa (P < 0.001). Repeat LSM at liver biopsy performed a median 3 months after screening showed a significant decrease (<12 kPa) among 30% (six of 20), and this was independent of alcohol consumption, BMI, age and gender. In 29 patients where liver biopsy was performed a LSM ≥ 16 kPa predicted cirrhosis with 88.9% sensitivity and 90% specificity. CONCLUSIONS Transient elastography is a feasible screening tool for cirrhosis among drug users. Transient elastography identifies severe liver fibrosis in a significant proportion of drug users with hepatitis C infections but management should not be based on a single elevated liver stiffness measurement.