Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up.CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.

Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues

AIM:To compare the differences in kinetics,distribution,and toxicity of triamcinolone acetonide(TA)between the injection methods,sub-Tenon and intravitreal injections in rabbit ocular tissues.METHODS:TA was injected into the vitreous or the sub-Tenon in rabbits.For pharmacokinetic study,rabbits were sacrificed periodically and then TA in blood and ocular tissues(retina/choroids,vitreous,and aqueous humor)were measured over 91 d.For toxicological study,clinical signs,slit-lamp microscopic examination,ophthalmological test were performed.The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution,and then paraffin embedded for histological investigation.RESULTS:Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon.Conversely,TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma.Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection.Meanwhile,technicassociated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection.CONCLUSION:There are significant differences in kinetics and distribution of TA in vitreous body,aqueous humor and plasma,between the two injection methods.Although further study is needed to explain the species difference between human and rabbit,it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods.Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself,respectively.

A Pilot Study: No Therapeutic Effect of L-Alanine in Patients with Nonalcoholic Steatohepatitis

Background: Mitochondrial dysfunction plays a pivotal role in the progression of nonalcoholic steatohepatitis (NASH). L-alanine was shown to restore ATP content and protect the liver in various liver injury models. Aim: To assess the safety and therapeutic effects of long-term administration of L-alanine in patients with NASH, we conducted a pilot trial. Methods: Patients with NASH were enrolled and treated with 6 - 18 g/day L-alanine for 12 months and monitored for serum aminotransferases and renal function. Liver histology was obtained at baseline and 12 months. Changes in serum aminotransferase were assessed by differences from entry and rate of change per month using all available measures. Changes in liver histology were assessed by differences in Brunt scores of steatosis, lobular inflammation, and fibrosis. Results: Nine patients were enrolled and six completed the treatment. The reasons of the study withdrawal were nausea (n = 1), planned bariatric surgery (n = 1), and un-specified reason (n = 1). One participant experienced exacerbation of pre-existing renal failure that required hospitalization, although the medication was safely resumed after 2-week cessation and treatment was completed. Serum alanine aminotransferase (ALT) (?24.8 ± 32.1 IU/L vs.0, p = 0.11) and aspartate aminotransferase (AST) (?8 ± 16.2 1IU/L vs. 0, p = 0.28) were improved in 4 and 3 of the 6 completed participants, while rate of ALT and AST change per month showed improvement over time (negative slope) in 5 and 4 of the 6. Liver histology did not change significantly. Conclusion: The 12-month administration of L-alanine seems to be safe, but did not show significant therapeutic effects on serum aminotransferase or liver histology in patients with NASH, along with less than ideal tolerability.

Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology:epidemiological findings and pathobiological mechanisms

Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.

Nonalcoholic fatty liver disease: does sex matter?

Introduction The hallmark of nonalcoholic fatty liver disease(NAFLD)is the intrahepatocyte accumulation of lipids with or without necro-inflammatory changes and ballooning[i.e.,steatohepatitis or nonalcoholic steatohepatitis(NASH)],fibrosis,cirrhosis and hepatocellular carcinoma(HCC),which is observed in dysmetabolic individuals in the absence of competing causes of chronic liver disease such as excess alcohol consumption,viral infections,autoimmune or hereditary conditions and steatogenic medications(1).NAFLD represents an example of lipotoxicity caused by ectopic lipid accumulation.Even relatively modest amounts of ectopic lipid accumulation in normally lean organs(e.g.,liver,pancreas,heart,kidney and muscle)can trigger functional disturbance in the affected organs and a subsequent vicious circle of adverse metabolic consequences in predisposed individuals(1);this will eventually result in those hepatic and extra-hepatic manifestations and co-morbid conditions which are frequently observed in NAFLD patients.Under this perspective,NAFLD should be viewed as one of the systemic manifestations and consequences resulting from lipid overflow.