Abbreviations: CFR, case-fatality rate; FHF, fulminant hepatic failure; HEV, hepatitis E virus; IQR, interquartile range; LBW, low birth weight; NOS, Newcastle-Ottawa Scale;PRISMA, preferred reporting items for systematic reviews and meta-analysis; PROM, premature rupture of membranes. AbstractHepatitis E virus infection during pregnancy can have severe consequences for mother and child, such as vertical transmission, fulminant hepatic failure, even foetal or maternal mortality. The aim of this systematic review is to describe maternal, foetal and neonatal case-fatality rates as well as the prevalence of adverse outcomes in relation to hepatitis E virus infection during pregnancy. A systematic literature search was performed in Pubmed, Embase, Cochrane and CINAHL. Search terms included Pregnant, Women, Maternal, Infant, Foetal, Neonatal and Hepatitis E virus.Data were extracted using predefined data collection forms. All studies were quality assessed, either by the Newcastle-Ottawa Scale or by an adapted assessment scale for cross-sectional studies. We found 23 eligible studies, all observational, which were included in this systematic review with a total of 1338 cases. The median maternal, foetal and neonatal case-fatality rates were 26% (IQR 17%-41%), 33% (IQR 19%-37%) and 8% (IQR 3%-20%), respectively. Adverse outcomes such as fulminant hepatic failure, preterm labour, postpartum haemorrhage, low birth weight and vertical transmission were reported. The two studies that reported the highest prevalence of fulminant hepatic failure also reported the highest case-fatality rates. The median prevalence of fulminant hepatic failure was 45.3%. This systematic review found a high case-fatality rate among pregnant women infected with hepatitis E virus and a high rate of adverse outcomes among these women and their children. The results from this review mainly apply to hospital settings and symptomatic pregnant women from endemic countries. K E Y W O R D Sfoetus, hepatitis E virus, mortality, pregnant women, systematic review |

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.

BackgroundChronic 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 methodsPatients 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.ResultsOf 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.ConclusionAlcohol 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.

Background and aimsChronic 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.MethodsConsecutive 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.ResultsWe 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).ConclusionWe 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.

MRs were high among patients with CHC with or without cirrhosis compared with the general population. Curing CHC was associated with a reduction in MR among cirrhotic patients, but the MR remained higher than the general population.

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.

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.

SummaryCirrhosis 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.