Sofie Hallager

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

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

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections: A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Mortality in patients with Chronic Hepatitis C and cirrhosis compared to the general population: a Danish cohort study

Background Knowledge of mortality in patients with Chronic Hepatitis C (CHC) with cirrhosis is limited. This study aimed to estimate all-cause mortality among CHC patients with and without cirrhosis in Denmark compared to the general population. Methods Patients registered in The Danish Database for Hepatitis B and C with CHC and a liver fibrosis assessment were eligible for inclusion. Liver fibrosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Up to 20 sex- and age-matched individuals per patient were identified in the general population. Data were extracted from nationwide registries. Results 3,410 CHC patients (1,014 with cirrhosis), and 67,315 matched individuals were included. Adjusted mortality rate ratios (MRR) between patients with and without cirrhosis and their comparison cohorts were 5.64 [CI95% 4.76; 6.67] and 1.94 [1.55; 2.42], respectively. Cirrhosis among patients was associated with a MRR of 4.03 [3.43; 4.72]. A cure for CHC was associated with a MRR of 0.64 [0.40; 1.01] among cirrhotic patients and 2.33 [1.47; 3.67] compared to the general population. Conclusions Mortality was high among CHC patients with and without cirrhosis compared to the general population. Curing CHC was associated with reduced mortality among cirrhotic patients but remained higher than the general population.

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.

Antiretroviral therapy adherence strategies used by patients of a large HIV clinic in Lesotho

A high degree of adherence to antiretroviral therapy (ART) in patients infected with human immunodeficiency virus (HIV) is necessary for long term treatment effects. This study explores the role of timing of ART intake, the information patients received from health workers, local adherence patterns, barriers to and facilitators of ART among 28 HIV-positive adults at the Senkatana HIV Clinic in Maseru, Lesotho. This qualitative, semi-structured interview study was carried out during February and March of 2011 and responses were analyzed inspired by the Grounded Theory method. Results were then compared and discussed between the authors and the main themes that emerged were categorized. The majority of the respondents reported having missed one or more doses of medicine in the past and it was a widespread belief among patients that they were required to skip the dose of ART if they were “late”. The main barriers to adherence were interruptions of daily routines or leaving the house without sufficient medicine. The use of mobile phone alarms, phone clocks and support from family and friends were major facilitators of adherence. None of the patients reported to have been counseled on family support or the use of mobile phones as helpful methods in maintaining or improving adherence to ART. Being on-time with ART was emphasized during counseling by health workers. In conclusion, patients should be advised to take the dose as soon as they remember instead of skipping the dose completely when they are late. Mobile phones and family support could be subjects to focus on during future counseling particularly with the growing numbers of mobile phones in Africa and the current focus on telemedicine.

Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation

OBJECTIVES We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark. MATERIALS AND METHODS In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause. RESULTS In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91). CONCLUSIONS In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.

Late Presentation for Care Among Patients With Chronic Hepatitis C: Prevalence and Risk Factors

Abstract Patients with chronic hepatitis C may have advanced fibrosis at first evaluation. Using the European Association for the Study of the Liver (EASL) definition (FibroScan® >9.5 kPa) for “late presenter for care” (LP), we found that 32% (169 of 527) of patients were LP. Being a LP was associated with increasing age and a history of alcohol overuse.

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: a nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha‐fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL−1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.