Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.

HLA-B*35:01 and Green Tea-Induced Liver Injury.

BACKGROUND AND AIMS: Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury. APPROACH AND RESULTS: Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5). CONCLUSIONS: Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.

Hepatic function and antioxidant activity in diabetic rats subjected to diet supplemented with multimixture / Función hepática y actividad antioxidante en ratas diabéticas con dieta suplementada con multimezcla

Introduction: Food and dietetic components have received considerable attention as auxiliary feeding resources on controlling of chronic non-transmissible diseases, among them diabetes. This study evaluated the effect of supplementary diet with multimixture based on linseed, sesame, oats and sunflower seeds on the hepatic function and antioxidant activity of diabetic rats. Methods: Male rats were distributed on groups of seven animals: diabetic control (DC), diabetics subject to multimixture diet (DM), diabetic with insulin (DI), and normal control (NC). The treatment was started on the 5th day after diabetes induction with 40 mg/kg i.v. streptozotocin on tampon citrate and kept during 50 days. Results: The ethereal extract of the supplemented diet showed a higher content of phenolics (p < 0.05) compared to other extracts of the supplemented diet and the ethereal extract of the standard diet. There was no difference in antioxidant in vitro activity of the utilized diets. Concerning to transaminases, signifi cant bigger ALT levels (p < 0.05) were present on diabetic groups compared to NC. The relative liver weight on diabetic groups was significantly higher (p < 0.001) compared to NC group. Non-proteic sulfhydryl group levels were significantly higher (p < 0.05) on DM and I groups when compared to DM and NC. Only the treatment with insulin resulted in an improvement of antioxidant activity concerning to hepatic catalase. The supplementation with multimixture did not improve the metabolic control of diabetes. Conclusion: The multimixture treatment showed an isolated improvement on antioxidant activity in the hepatic tissue, evidenced by the increasing on non-proteic sulfhydryl group levels (AU)

Introducción: alimentos y componentes de la dieta han recibido considerable atención como recursos auxiliares en el control de las enfermedades crónicas, como la diabetes. Este estudio evaluó el efecto de la dieta suplementada con base de linaza multimezcla, sésamo, avena y semillas de girasol en la función hepática y la actividad antioxidante de ratas diabéticas. Métodos: las ratas macho fueron divididas en grupos de siete animales: control de la diabetes (CD), diabéticos sometidos a dieta multimezcla (DM), diabéticos con insulina (DI), y control normal (CN). El tratamiento se inició en el quinto día después de la inducción de la diabetes con estreptozotocina 40 mg/kg i.v. en tampón citrato y se mantuvo durante 50 días. Resultados: la dieta extracto etéreo complementado tenía el contenido fenólico más alto (p < 0,05) que los otros extractos de la suplementación de la dieta y el extracto de éter de la comida estándar. No hubo diferencia en la actividad antioxidante in vitro de la alimentación usada. A medida que las transaminasas, los niveles de ALT significativamente mayor (p < 0,05) estuvieron presentes en el grupo de diabéticos en comparación con CN, el peso relativo del hígado en el grupo de diabéticos fue significativamente mayor (p < 0,001) en comparación con el grupo CN. Los grupos sulfhidrilo de los niveles de proteína no fueron significativamente mayores (p < 0,05) en los grupos F e I comparados con CN y CD. El tratamiento con insulina resultó en una mejora de la actividad antioxidante con respecto a la catalasa hepática. Conclusión: la suplementación con multimezcla no mejora el control metabólico de la diabetes. El tratamiento con multimezcla aislado mostró una mejora en la actividad antioxidante en el tejido hepático, como se evidencia por el aumento de los niveles de grupos sulfhidrilo no proteicos (AU)

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients.

ETHNOPHARMACOLOGICAL RELEVANCE: The objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. MATERIALS AND METHODS: Of 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. RESULTS: A total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. CONCLUSIONS: The prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake.