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Metabolic disorders appear to be the biggest risk factors for hepatocellular carcinoma (HCC) and have increased in the last decade, new US evidence suggests.
Researchers at the National Cancer Institute, Bethesda, used data from the Surveillance, Epidemiology, and End Results-Medicare linkage to calculate population attributable fractions (PAFs) for each risk factor over time. A total of 10, 708 patients with HCC who were diagnosed between 2000 and 2011 were compared with 332,107 cancer-free controls residing in the Surveillance, Epidemiology, and End Results areas.
Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%) and whites (PAF, 34.8%), whereas HCV had the largest PAF among black people (PAF, 36.1%) and Asians (PAF, 29.7%).
Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% to 36%. In contrast, the PAFs of alcohol-related disorders and HCV remained stable.
Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. Makarova-Rusher OV, Altekruse SF, McNeel TS et al. Cancer. 2016 Mar 21 [Epub ahead of print]
A UK study suggests an increased risk of hepatotoxicity with high doses of the statin atorvastatin when compared to sim vastatin.
Researchers at the University of Glasgow used the UK General Practice Research Database (GPRD) to identify 164,407 patients with a first prescription for sim vastatin and 76,411 with atorvastatin between 1997 and 2006. None of the patients had a prior record of liver disease, alcohol-related diagnosis, or liver dysfunction.
Moderate to severe hepatotoxicity developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio for all atorvastatin relative to simvastatin was 1.9.
High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4,075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS].
Adjusted hazard ratios compared to LDS were 7.3 for HDA, 1.4 for LDA and 1.5 for HDS.
High dose atorvastatin associated with increased risk of significant
hepatotoxicity in comparison to simvastatin in UK GPRD cohort. Clarke AT, Johnson PC, Hall GC et al. PLoS One. 2016 Mar 16;11(3):e0151587
New research suggests epigallocatechin-3-gallate (EGCG), a major component of green tea, could be an effective anti-HBV agent.
Using fluorescence quenching and affinity binding, researchers at Henan Agricultural University, Zengzhou, China, showed EGCG to be an important transcriptional regulator of the HBV genome. It achieves this by interacting with farnesoid X receptor alpha (FXRα).
Luciferase assay showed that EGCG effectively inhibited the transcription of the HBV promoter dose-dependently when expression plasmids of FXRα and retinoid X receptor α (RXRα) were co-transfected into HEK293 cells.
These results indicated the down-regulation of the HBV antigen and the decrease in the transcriptional activation of the HBV EnhII/core promoter by FXRα/RXRα are mainly because of the interaction between EGCG and FXRα. Therefore, say the researchers, EGCG, an antagonist of FXRα in liver cells, has the potential to be employed as an effective anti-HBV agent.
Epigallocatechin gallate inhibits hepatitis B virus via farnesoid X receptor alpha. Xu J, Gu W, Li C et al. J Nat Med. 2016 Mar 11. [Epub ahead of print]
HCV infections can be identified and fibrosis staged using commonly available electronic medical record (EMR)-based algorithms.
So say researchers at the NorthShore University Health System, Portland, USA. The team performed a pilot study to identify all HCV-infected patients in a large healthcare system, and predict their fibrosis stage on the basis of demographic and laboratory data from their EMRs.
The liver biopsies of 191 HCV patients were graded using the Ishak and Metavir scoring systems. Demographic and laboratory data were extracted from the EMR and used to calculate the aminotransferase to platelet ratio index, Fib-4, Fibrosis Index, Forns, Göteborg University Cirrhosis Index, Lok Index and Vira-HepC.
In total, 869 HCV-infected patients were identified from a population of more than 1m. In the subgroup of patients with liver biopsies, all seven algorithms were significantly correlated with the fibrosis stage. The degree of correlation was moderate, with correlation coefficients ranging from 0.22 to 0.60.
For the detection of advanced fibrosis (Metavir three or four), the areas under the receiver operating characteristic cure ranged from 0.71 to 0.84, with no significant differences between the individual scores. Sensitivities, specificities, and positive and negative predictive values were within the previously reported range. All scores tended to perform better for higher fibrosis stages.
Identification and fibrosis staging of Hepatitis C patients using the electronic medical record system. Anand V, Hyun C, Khan QM et al. J Clin Gastroenterol. 2016 Mar 11. [Epub ahead of print]
Obesity has been shown to be the major risk factor for cirrhosis and advanced fibrosis in young Hispanic males.
Researchers studied 2,466 participants in the community-based Cameron County Hispanic Cohort in South Texas. Aspartate transaminase to Platelet Ratio Index (APRI) was used to predict cirrhosis.
The prevalence of cirrhosis using APRI=2 was 0.94%, which is nearly four-fold higher than the national USA prevalence. Using APRI=1, the overall prevalence of cirrhosis/advanced fibrosis was 3.54%. In both analyses, the highest prevalence was in males, specifically in the 25-34 age group.
Risk factors independently associated with APRI=2 and APRI=1 included HCV, diabetes and central obesity with a remarkable population attributable fraction of 52.5% and 65.3% from central obesity, respectively.
Excess alcohol consumption was also independently associated with APRI=2. The presence of patatin-like phospholipase domain-containing-3 gene variants was independently associated with APRI=1 in participants over 50 years of age.
Cirrhosis and advanced fibrosis in Hispanics in Texas: the dominant contribution of central obesity. Jiao J, Watt GP, Lee M et al. PLoS One. 2016 Mar 7;11(3):e0150978
New evidence from the USA suggests HBV care for chronically infected mothers may be inadequate following pregnancy.
Researchers assessed the quality of HBV care in 243 HBsAg-positive mothers who had sought pre-natal care at Massachusetts General Hospital.
More than a third of the women were first diagnosed with HBV infection at a pre-natal visit, and one third did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients.
One were at high-risk for HCC based on American Association for the Study of Liver Diseases (AASLD) criteria, yet only 33% of these women underwent timely imaging. Nearly half never saw a liver specialist for their HBV care.
In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist.
The researchers say the HBV care was remarkably inadequate and discontinuous. They suggest that, as HBV infection is already being
identified pre-natally, quality improvement measures encompassing obstetricians, primary care providers and hepatologists are needed to ensure that HBV-infected women are linked to care post-pregnancy.
Discontinuity of care for mothers with chronic hepatitis B diagnosed during pregnancy. Rajbhandari R, Barton K, Juncadella AC et al. J Viral Hepat. 2016 Mar 4 [Epub ahead of print]
Daclatasvir plus peginterferon-ribavirin (PR) was the most effective direct-acting antiviral agent regimen in SVR12 and SVR24, but carried an increased adverse events profile in HCV genotype one.
Researchers at Wenzhou Medical University, China, conducting a literature review found 22 eligible randomised controlled trials. Compared with PR, daclatasvir plus PR (odds ratio 8.90), faldaprevir plus PR (odds ratio 3.72), simeprevir plus PR (odds ratio 3.59) and sofosbuvir plus PR (odds ratio 4.69) yielded a significant effect in improving SVR12. Consistently, simeprevir plus PR (odds ratio 3.49), sofosbuvir plus PR (odds ratio 4.51) and daclatasvir plus PR (odds ratio 4.77) also improved the rates of SVR24.
With respect to adverse events, compared with PR, ledipasvir plus sofosbuvir plus PR (odds ratio 2.13) conferred a significant advent event in nausea, whereas daclatasvir plus PR (odds ratio 0.20 and 0.18, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR.
Systematic review and network meta-analysis of randomised controlled trials: comparative effectiveness and safety of direct-acting antiviral agents for treatment-naive Hepatitis C Genotype 1. Zhu GQ, Zou ZL, Zheng JN et al. Medicine (Baltimore). 2016 Mar;95(9):e3004
There is a high global prevalence of HCV in all people with HIV, particularly those who inject drugs.
A global systematic review and meta-analysis carried out by an international team of researchers found 783 studies published between 2002 and 2015, resulting in 902 estimates of the prevalence of HIV/HCV co-infection.
The analysis showed co-infection was present in 2.4% of those with HIV within general population samples, 4.0% within pregnant or heterosexually exposed samples, 6.4% in men who have sex with men, and 82.4% in people who inject drugs.
The odds of HCV infection were six times higher in people living with HIV (5.8) than their HIV-negative counterparts.
Worldwide, there were 37million people infected with HIV and 115million people with antibodies to HCV. The study found approximately 2,278,400 HIV/HCV co-infections, of which 1,362,700 were in people who inject drugs, equalling an overall co-infection prevalence in HIV-infected individuals of 6.2%.
The research, which was funded by the World Health Organization, highlighted the importance of routine HCV testing in all HIV-infected individuals, but especially in people who inject drugs. It also identified a need to improve country-level surveillance of HCV prevalence across different population groups in all regions.
Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Platt L, Easterbrook P, Gower E et al. Lancet Infect Dis. 2016 Feb 24 [Epub ahead of print]
Offering routine blood-borne virus (BBV) screening in emergency departments (EDs) uncovered a high number of hepatitis, particularly HCV, infections.
During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in Glasgow, Leeds, Leicester and London offered adults having blood taken as part of routine care HIV, HBV and HCV tests. The areas involved all have high HIV prevalence and patients who tested positive were linked to care.
A total of 7,807 patients had blood taken during their ED visit and 2,118 were tested for BBVs. In all, 71 tests were positive, with 32 resulting in a new diagnosis. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged between 25 and 54 had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV.
The study authors calculated that, assuming the cost per diagnosis was £7, the cost per new case detected would be £988 for HCV, £1,351 for HBV and £2,478 for HIV. The authors also concluded that testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.
Incorporating HIV/hepatitis B virus/hepatitis C virus combined testing into routine blood tests in nine UK Emergency Departments: the "Going Viral" campaign. Orkin C, Flanagan S, Wallis E et al. HIV Med. 2016 Mar;17(3):222-30
At one year, telbivudine was superior to other nucleos(t)ide analogues (NAs) in HBeAg seroconversion, among other outcomes, in chronic HBV.
Researchers at Nanfang Hospital, Guangzhou, China, conducted a comprehensive and up-to-date network meta-analysis comparing the efficacy of NAs in patients with chronic HBV. A total of 75 randomised controlled trials (RCTs) were included in the systematic review, which was funded by Novartis.
At one year, telbivudine was associated with significantly higher rates of HBeAg seroconversion than adefovir (odds ratio 1.99), entecavir (odds ratio 2.00) and limivudine (odds ratio 1.49). It was linked to with significantly higher HBeAg loss than entecavir (odds ratio 1.85) and limivudine (odds ratio 1.62), with significantly higher aminotransferase (ALT) normalisation than limivudine (odds ratio 1.50), and with significantly higher rates of HBV DNA suppression than adefovir (odds ratio 2.77) and limivudine (odds ratio 2.97).
At two years, however, the relative efficacy outcomes were not statistically significant.
Effect of telbivudine versus other nucleos(t)ide analogs on HBeAg seroconversion and other outcomes in patients with chronic Hepatitis B: a network meta-analysis. Liang X, Fan R, Sun J et al. Adv Ther. 2016 Feb 26. [Epub ahead of print]