Flavonoids from Barnebydendron riedelii leaf extract mitigate thioacetamide-induced hepatic encephalopathy in rats: The interplay of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.

Phytochemical investigation of the butanol fraction (BUF) derived from the 70% aqueous methanolic leaf extract of Barnebydendron riedelii led to the isolation of three flavonoid glycosides; kaempferol-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-galactopyranoside and quercetin-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside. Docking studies were fulfilled to validate the possible bio-properties of BUF toward nuclear factorkappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). The protective role of BUF against behavioral, biochemical, molecular, histopathological and immunohistochemical alterations in thioacetamide (TAA)-induced hepatic encephalopathy in rats was investigated. The toxicological studies indicated that BUF was safe up to 2000 mg/kg bw. Prior to TAA intoxication, rats were orally treated with either BUF at multiple doses (70, 140 and 280 mg/kg bw) or lactulose (8 mL/kg bw) for 14 consecutive days. On the 13th and the 14th day, TAA (200 mg/kg bw/day) was intraperitoneally injected. The BUF significantly improved motor impairment, ameliorated cognitive deficits and attenuated TAA-induced hepatotoxicity. Moreover, BUF controlled the inflammatory processes by suppressing the hepatic inflammatory cytokine; interleukin-6 (IL-6) as well as its pro-inflammatory mediator; NF-κB supporting the molecular docking assessment. The brain neurotransmitters; dopamine, serotonin and noradrenaline, as well as ammonia levels were improved in BUF-treated TAA-intoxicated animals in a dose-dependent manner. Furthermore, BUF administration to TAA-intoxicated rats modulated the Nrf2 and heme oxygenase 1 (HO-1) genes expression in liver and brain tissues. The histological evaluation showed that pretreatment of TAA-intoxicated rats with BUF ameliorated the degenerative effects of TAA on liver and brain tissues as well as reduced the activation of cellular apoptotic marker; caspase-3 and glial fibrillary acidic protein (GFAP+) astrocytes. In conclusion, the observed hepato-neuroprotective effect of BUF is attributed to its flavonoidal content through its modulatory effects on of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.

Hospitalizations for Autoimmune Hepatitis Disproportionately Affect Black and Latino Americans.

OBJECTIVES: The healthcare burden of autoimmune hepatitis (AIH) in the United States has not been characterized. We previously showed that AIH disproportionately affects people of color in a single hospital system. The current study aimed to determine whether the same disparity occurs nationwide. METHODS: We analyzed hospitalizations with a primary discharge diagnosis corresponding to the ICD-9 code for AIH in the National Inpatient Sample between 2008 and 2012. For each racial/ethnic group, we calculated the AIH hospitalization rate per 100,000 population and per 100,000 all-cause hospitalizations, then calculated a risk ratio compared to the reference rate among whites. We used multivariable logistic regression models to assess for racial disparities and to identify predictors of in-hospital mortality during AIH hospitalizations. RESULTS: The national rate of AIH hospitalization was 0.73 hospitalizations per 100,000 population. Blacks and Latinos were hospitalized for AIH at a rate 69% (P<0.001) and 20% higher (P<0.001) than whites, respectively. After controlling for age, gender, payer, residence, zip code income, region, and cirrhosis, black race was a statistically significant predictor for mortality during AIH hospitalizations (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.43, 5.47). CONCLUSIONS: Hospitalizations for AIH disproportionately affect black and Latino Americans. Black race is independently associated with higher odds of death during hospitalizations for AIH. This racial disparity may be related to biological, genetic, environmental, socioeconomic, and healthcare access and quality factors.

Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China.

AIM: To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy (MHE) among Chinese individuals with cirrhosis. METHODS: The five tests of PHES, number connection test-A (NCT-A), number connection test-B, serial dotting test, line tracing test and digit symbol test (DST), were administered to all enrolled subjects in a quiet room with sufficient light. Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination. Based on the nomograms of healthy volunteers, the patients were classified as having MHE when their PHES was less than -4. RESULTS: In total, 146 healthy volunteers completed all the PHES tests. Age and education years were confirmed to be predictors of all five tests. In total, 53 patients with liver cirrhosis completed the PHES. Of the patients with liver cirrhosis, 24 (45.3%), 22(41.5%) and 7(13.2%) had Child-Pugh grades A, B and C, respectively. MHE was diagnosed in 26 patients (49.1%). Compared with compensated cirrhotic patients (Child A), decompensated cirrhotic patients (Child B and C) had a higher proportion of MHE (65.5% vs 29.2%). No differences in age and education years were found between the MHE and non-MHE groups. NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9% and a specificity of 96.3% (AUC = 0.866, K = 0.735). CONCLUSION: The proportion of MHE is associated with liver function. NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy.

AIM: To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B, liver cirrhosis, including patients with minimal hepatic encephalopathy (MHE). METHODS: The SF-36 and CLDQ were administered to 160 healthy volunteers, 20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. Six domains of CLDQ were assessed: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry. RESULTS: Compared with healthy controls (96.9 +/- 4.5, 86.6 +/- 18.4, 90.1 +/- 12.5, 89.0 +/- 5.7, 87.5 +/- 4.3, 95.8 +/- 7.1, 88.5 +/- 15.9, 88.7 +/- 5.2 in SF-36 and 6.7 +/- 0.5, 6.1 +/- 0.6, 6.3 +/- 0.6, 6.5 +/- 0.5, 6.3 +/- 0.5, 6.8 +/- 0.4 in CLDQ), patients with chronic hepatitis B (86.3 +/- 11.0, 68.8 +/- 21.3, 78.9 +/- 14.4, 60.8 +/- 10.5, 70.8 +/- 8.6, 76.1 +/- 12.6, 50.0 +/- 22.9, 72.2 +/- 10.6 and 5.5 +/- 1.0, 4.5 +/- 1.0, 5.2 +/- 1.1, 5.3 +/- 0.9, 4.8 +/- 0.9, 4.9 +/- 1.0) and cirrhosis (52.8 +/- 17.4, 32.8 +/- 27.9, 61.6 +/- 18.9, 30.2 +/- 18.3, 47.9 +/- 20.1, 54.0 +/- 19.2, 28.9 +/- 26.1, 51.1 +/- 17.8 and 4.7 +/- 1.2, 3.9 +/- 1.2, 4.7 +/- 1.2, 4.7 +/- 1.3, 4.7 +/- 1.0, 4.4 +/- 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ, especially SF-36. CONCLUSION: The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.