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Entecavir in children and adolescents with chronic HBV is safe and shows clinical benefits in short-term biochemical and virologic responses, a new study concluded.
In the study, at the National Taiwan University Hospital, group one comprised nine treatment-naïve patients (median aged 12.2 years) who had been HBeAg seropositive for more than six months, and had alanine aminotransferase (ALT) of more than two times the upper limit of normal value (30 IU/L). They received entecavir at a dose of 0.015 mg/kg/d, with a maximal dose of 0.5 mg daily, for at least 52 weeks. Another 27 untreated chronic HBV patients matched for age, sex, ALT levels, and HBeAg status were recruited as the control group.
The entecavir-treated patients achieved rapid ALT normalisation (all before eight months of treatment) compared with the control group and had a greater chance of achieving undetectable HBV DNA levels at Week 52 after treatment (55.6% versus 11.1%).
The cumulative incidence rates of HBeAg seroconversion were similarly high in both groups (entecavir group 44% at one year and 78% at two years; control group 37% and 63%, respectively). The entecavir group also had a trend of better complete response than the control group (22.2% versus 0%). None of the entecavir-treated patients reported significant adverse effects.
Entecavir treatment in children and adolescents with chronic hepatitis B virus infection. Chang KC, Wu JF, Hsu HY et al. Pediatr Neonatol. 2015 Dec 23 [Epub ahead of print]
Tacrolimus with entecavir was fast and effective at inducing remission of HBV-associated glomerulonephritis in adults, a Chinese study reported.
The study authors have suggested the two may have a synergistic antiviral effect used together.
In the study, at Guangdong General Hospital, 23 HBV patients with biopsy-proven membranous nephropathy received tacrolimus (0.05mg/kg/day) in combination with entecavir over 24 weeks, whereas 19 received entecavir monotherapy.
The probability of proteinuria remission in the combination group was 69% after 12 weeks and 87% after 24, while in the monotherapy group it was 26% and 42%, respectively.
The mean time to partial or complete remission was 18.6 weeks in the combination patients and 34.3 weeks in the monotherapy group. There was a decrease in the HBV DNA titre in all patients with active HBV replication. None of the HBV carriers in the combination group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The tacrolimus target trough concentration was 5-10ng/ml.
The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication. Wang L, Ye Z, Liang H et al. Clin Chim Acta. 2016 Jan 22 [Epub ahead of print]
The proportion of HCV-infected Americans with cirrhosis increased from 6.6% to 17.0% over the past two decades.
A new study found the prevalence of cirrhosis was highest among individuals who were unaware of their HCV infection.
Researchers at Stanford University School of Medicine used National Health and Nutrition Examination Survey (NHANES) data to identify adults with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for Eras 1 (1988-94), 2 (1999-2006) and 3 (2007-12) by using FIB-4 > 3.25 and APRI > 2.0, respectively.
Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% of HCV-infected adults in Era One, 7.6% in Era Two and 17.0% in Era Three had cirrhosis.
In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio 1.04), diabetes (odds ratio 2.33) and obesity (odds ratio 2.96). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used.
The researchers say these data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease.
Increasing prevalence of cirrhosis among US adults aware or unaware of their chronic hepatitis C virus infection. Udompap P, Mannalithara A, Heo N et al. J Hepatol. 2016 Jan 22 [Epub ahead of print]
New genetic studies show that the anti-HBV nucleotide analogue, entecavir, has a genotoxic effect.
To evaluate its genotoxic mechanisms, researchers at Sichuan University, China, analysed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways.
The results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir.
XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells.
The researchers concluded these genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity.
Genetic evidence for genotoxic effect of entecavir, an anti-hepatitis B virus nucleotide analogue. Jiang L, Wu X, He F et al. PLoS One. 2016 Jan 22;11(1):e0147440
In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival.
A new multicentre study also found an increased risk of hepatic decompensation in these patients.
A total of 250 subjects in Australia, Cuba and Spain, with compensated HCV-related cirrhosis and without known diabetes, underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks.
At baseline, 67 had Type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (hazard ratio 2.2) and hepatic decompensation events (hazard ratio 1.9) were significantly higher in those with diabetes.
Patients with a HOMA-IR >5 showed higher rates of mortality (hazard ratio 2.2). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (hazard ratio 1.7).
Overall, two-hour plasma glucose was the most robust predictor of overall mortality (hazard ratio 2.5) and decompensation (hazard ratio 2.7).
Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis. Calzadilla-Bertot L, Vilar-Gomez E, Torres-Gonzalez A et al. Dig Liver Dis. 2015 Dec 25 [Epub ahead of print]
Two new studies demonstrate how alpha-fetoprotein (AFP) remains a valuable biomarker for predicting hepatocellular carcinoma (HCC) in hepatitis patients.
A Chinese study concluded that serum AFP was of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and suggests its use as a biomarker in HBV endemic area like south east Asia (1).
Researchers from Peking University Health Science Centre studied 318 HBV patients, 731 cirrhosis patients and 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum HBsAg positive HCC patients was significantly higher than that in HBsAg negative HCC patients (79.55% versus 56.49%). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml versus 40.82ng/ml).
In addition, Kaplan-Meier curve analysis revealed that lower pre-operative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients aetiologically irrelevant to HBV infection.
A Brazilian study has suggested AFP could be used to distinguish between patients with HCC and cirrhosis or HCV, and that vascular endothelial growth factor (VEGF) could be a potential biomarker for HCC (2).
Researchers at Faculdade de Medicina de São José do Rio Preto evaluated the influence of the VEGF-C936T polymorphism on the prognosis of HCC, cirrhosis and HCV infection. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls.
The genotype CC (frequencies between 63.24% and 76.79%) and the C allele (absolute frequencies from 0.816 to 0.884) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 pg/mL) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 pg/mL) compared to those in the other groups.
The same trend occurred with AFP levels (HCC 8.522; cirrhosis 12.7; HCV 4.6; control 2.7 ng/mL). Levels of VEGF and AFP showed sensitivity of 65% and 28% and specificity of 85 and 99%, respectively, for HCC patients.
1. Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma. Yao M, Zhao J, Lu F. Oncotarget. 2016 Jan 13.[Epub ahead of print]
2. Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma. Yvamoto EY, Ferreira RF, Nogueira V et al. Genet Mol Res. 2015 Dec 21;14(4):17453-62
Aspirin may play a role in the prevention and treatment of fibrosis among adults with suspected chronic liver diseases, a US study suggests.
The study, at Harvard Medical School, Boston, used data from the National Health and Nutrition Examination Survey III to identify 1,856 individuals with suspected chronic liver disease.
The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected chronic liver disease compared to those without. The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses.
The researchers suggest aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.
Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Jiang ZG, Feldbrügge L, Tapper EB et al. Aliment Pharmacol Ther. 2016 Jan 7 [Epub ahead of print]
Children receiving liver transplants (LTs) do not present with significant cardiovascular risk factors (CVRF), a new French study suggests.
Researchers at Lyon University retrospectively assessed CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT) in 31 children who underwent LTs between 1990 and 2000. Their median age at LT was 14 months and the median follow-up after LT was 11.9 years.
In these children, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients were smokers or diabetic. High TC and TG were both observed in 6.5%. The mean c-IMT for male patients was 1.22mm and for female patients,1.58 mm.
Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the fifth percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05).
Lipid profile and cardiovascular risk factors in paediatric liver transplant recipients. Roblin E, Dumortier J, Di Filippo M et al. Pediatr Transplant. 2016 Jan 11 [Epub ahead of print]
Adding a nucleoside polymerase inhibitor with intermediate antiviral potency to regimens containing a first-generation protease inhibitor (PI) may benefit difficult-to-treat HCV g1 patients.
Two studies have demonstrated the approach increased sustained virological response (SVR) rates and reduced relapse rates in this group.
Researchers studied the incremental benefits associated with adding mericitabine (nucleoside analogue inhibitor of HCV polymerase) to a PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomised multicentre phase two trials. DYNAMO 1 used boceprevir and DYNAMO 2, telaprevir.
Overall, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60% to 70% in DYNAMO 1 and of 71% to 96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials.
The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial.
Mericitabine and either boceprevir or telaprevir in combination with peginterferon alfa-2a plus ribavirin for patients with chronic hepatitis C genotype 1 infection and prior null response: the randomized DYNAMO 1 and DYNAMO 2 studies. Wedemeyer H, Forns X, Hézode C et al. PLoS One. 2016 Jan 11;11(1):e0145409
In a US surgical intensive care unit (SICU), patients with HCV had an increased incidence of infectious complications compared with non-HCV patients.
A total of 1,941 patients admitted to the SICU at Houston’s Baylor College of Medicine between 2008 and 2012 were studied. Those who were HCV-positive had a higher overall incidence of infectious complications (25% versus 18%), particularly ventilator-associated pneumonia (VAP) and bacteraemia. The increased incidences of VAP and bacteraemia persisted when cirrhotic patients were excluded.
Prolonged intubation (odds ratio 2.1), abdominal surgery (odds ratio 1.6), and model for end-stage liver disease ≥ 15 (odds ratio 1.4) were independent predictors of SICU infectious complications.
Hepatitis C status and infectious complications in the surgical intensive care unit: a retrospective analysis of 1,941 consecutive patients. Kueht M, Bebko S, Helmick R et al. Am J Surg. 2015 Dec 13 [Epub ahead of print]