Endotoxinemia contributes to steatosis,insulin resistance and atherosclerosis in chronic hepatitis C: the role of pro-inflammatory cytokines and oxidative stress

Purpose

Endotoxin is a component of the outer membrane of gram-negative bacteria that live in the intestine. Endotoxinemia is reported in non-alcoholic fatty liver disease and in cirrhotic patients, causing various biological and clinical effects in the host. It is not known whether endotoxinemia occurs in chronic hepatitis C patients (CHC), therefore we evaluated the occurrence of endotoxinemia and its effect on inflammation, liver damage, insulin resistance (IR) and atherosclerosis.

Methods

Consecutive CHC patients assessed by liver biopsy were enrolled. Endotoxinemia was evaluated by LAL test. IR was estimated by HOMA-IR. Serum TNF-α, IL-8, adiponectin and MCP-1 were measured with ELISA tests. Oxidative stress was estimated by circulating IgG against malondialdehyde adducts with human serum albumin (MDA-HAS). Carotid atherosclerosis was assessed by ultrasonography.

Results

Endotoxinemia was found in 60% of the 126 patients enrolled. A serum level-dependent association between endotoxinemia, steatosis (p?<?0.001) and HOMA-IR (p?<?0.006) was observed. Patients with endotoxinemia showed significant increase in TNF-α and IL8 levels. TNF-α correlated with steatosis (p < ?0.001) and HOMA-IR (p?<?0.03), whereas IL8 correlated with steatosis (p?= ?<0.001), TNF-α (p?<?0.04) and atherosclerosis (p?<?0.01). The highest levels of endotoxinemia were associated with oxidative stress and a higher prevalence of carotid atherosclerosis. Multivariate logistic regression analysis showed that the independent factors associated with endotoxinemia were hepatic steatosis, HOMA-IR, IL8 and MDA-HAS.

Conclusions

Endotoxinemia occurs with high frequency in CHC patients and contributes to the development of hepatic steatosis, IR and atherosclerosis through increased pro-inflammatory cytokines and oxidative stress. Anti-endotoxin treatment could be of clinical relevance.

     

Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy

OBJECTIVE: To assess gender differences in the long-term clinical, virological and immunological outcomes during highly active antiretroviral therapy (HAART). METHODS: This longitudinal observational multicentre study followed 2460 HIV-infected patients who had begun a protease inhibitor-based regimen for a median period of 43 months. Outcome measures were virological suppression (< 500 copies/ml), confirmed virological rebound after suppression, and death or new AIDS-defining illness (ADI). RESULTS: At baseline, 690 female patients (28.0%) had significantly lower age, higher prevalence of heterosexual contact and lower prevalence of intravenous drug use as risk factors for HIV infection compared with males. Furthermore, females had a lower number of AIDS-defining illnesses, higher CD4 cell counts and lower viral loads.No gender differences were reported in terms of proportion of patients achieving viral suppression or exhibiting rebound after achieving viral suppression. Female patients experienced reduced clinical progression during follow-up compared with males (P = 0.008) by Kaplan-Meier analysis; however this difference was not significant in an adjusted analysis. In a multivariate model, the interaction between gender and risk factor for HIV or viral load showed that female drug users and female patients with a baseline HIV RNA viral load of 10(4)-10(5) copies/ml had a favourable clinical outcome compared with males (P = 0.035 and P = 0.015, respectively). CONCLUSION: No differences were found between genders in terms of virological and immunological outcomes during long-term HAART. Nevertheless, a lower risk of clinical progression was reported among female patients with intermediate baseline viral load than in males.     

Colorectal cancer screening: The surgery rates they are a-changing. A nationwide study on surgical resections in Italy

Background

Growing evidence suggests that colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) reduces CRC incidence and surgical resection rates.

Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients

The aim of the study was to evaluate the hypothalamus-pituitary-adrenal (HPA) axis in patients (nine males, three females; mean age +/- sem 51 +/- 2 yr) with adult-onset GH deficiency (GHD) due to surgically treated pituitary tumors with preserved HPA function and without evidence of tumor recurrence before and during recombinant human (rh) GH replacement therapy (duration 31 +/- 6 months). HPA function was assessed by urinary free cortisol and morning serum cortisol levels as well as cortisol responses to 1 mug ACTH test (n = 7 patients) or insulin tolerance test (n = 5 patients) before and during rhGH therapy, the cut-off for the diagnosis of hypoadrenalism being a cortisol peak less than 18 microg/dl (<500 nmol/liter) after stimulatory tests. Serum cortisol and urinary free cortisol levels were significantly lower on therapy than before [7.6 +/- 0.8 vs. 11.5 +/- 0.9 microg/dl (208 +/- 22 vs. 317 +/- 24 nmol/liter), P < 0.01, and 19.6 +/- 2.5 vs. 32.2 +/- 3.2 microg per 24 h (54 +/- 7 vs. 89 +/- 9 nmol per 24 h), P < 0.05, respectively], whereas no change in cortisol-binding globulin levels was observed. Cortisol peak after either ACTH test or insulin tolerance test was lower on rhGH therapy than before [15.9 +/- 1.5 vs. 20.2 +/- 1.1 microg/dl (437 +/- 43 vs. 557 +/- 31), P = 0.01, and 13.1 +/- 2.6 vs. 20.4 +/- 1.4 microg/dl (362 +/- 71 vs. 564 +/- 37 nmol/liter), P = 0.03, respectively]. Accordingly, central hypoadrenalism was detected in nine of 11 patients. In conclusion, low GH and IGF-I levels, likely enhancing the conversion of cortisone to cortisol, may mask a condition of central hypoadrenalism. Therefore, the reassessment of HPA function in GHD patients during rhGH therapy is mandatory.     

The diagnostic yield of colonoscopy in hospitalized patients. An observational multicenter prospective study.

BackgroundColonoscopy demands a considerable amount of resources, and little is known about its diagnostic yield among inpatients.AimsTo assess indications, diagnostic yield and findings of colonoscopy for inpatients, and to identify risk factors for relevant findings and cancer.MethodsMulticentre, prospective, observational study including 12 hospitals. Consecutive adult inpatients undergoing colonoscopy were evaluated from February through November 2019.Results1,302 inpatients underwent colonoscopy. Diagnostic yield for relevant findings and cancer was 586 (45%) and 112 (8.6%), respectively. Adequate colon cleansing was achieved in 896 (68.8%) patients. Split-dose/same-day regimen was adopted in 847 (65%) patients. Factors associated to relevant findings were age ≥70 years (RR 1.32), male gender (RR 1.11), blood loss (RR 1.22) and adequate cleansing (RR 1.63). Age ≥70 years (RR 2.08), no previous colonoscopy (RR 2.69) and split-dose/same-day regimen (RR 1.59) significantly increased cancer detection. Implementing adequate cleansing and split-dose/same-day regimen in all patients would increase the diagnostic yield for any relevant findings and cancer from 43% to 70% and from 6% to 10%, respectively.ConclusionRelevant colorectal diseases and cancer were frequent among inpatients. Factors associated with detection of relevant findings were identified. Adequate colon cleansing and split-dose/same-day regimen significantly increased colonoscopy diagnostic yield.     

EtOH disrupts female mammalian puberty: age and opiate dependence

The major drug of abuse among teenagers in the United States continues to be ethanol (EtOH), but use is seen in children as young as nine. In the studies reported here, the impact of EtOH on biologic and hormonal parameters of puberty was assessed in female rats. Rats were fed a liquid diet containing EtOH, pair fed an identical liquid diet containing dextrimaltose instead of EtOH, or fed a liquid diet not containing EtOH ad libitum. Feeding was started at 21, 25, or 28 d of age. EtOH markedly delayed the age at vaginal opening (34.5±0.5 d in controls vs 48.5±2.4 d in EtOH animals; p<0.001), delayed the age at first estrous (40.9±0.6 d in controls vs 61.2±2.6 d in EtOH animals; p<0.001), increased the length of the estrous cycle, and decreased the number of proestrous days. EtOH, concomitant with reduced ovarian and uterine weight, decreased serum estradiol and progesterone. Associated with these changes in ovarian hormones there was a selective increase in follicle-stimulating hormone, but not luteinizing hormone. EtOH consistently reduced insulin-like growth factor-1. In general, EtOH-induced disruption was more severe the younger the animals were at the start of feeding. Opiate receptor blockade with naltrexone completely prevented the EtOH-induced delay in vaginal opening. The impact of EtOH on female puberty is dramatic, is an emerging public health problem, and deserves more study.