Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models

by Andrea Peloso, Stéphanie Lacotte, Quentin Gex, Florence Slits, Beat Moeckli, Graziano Oldani, Matthieu Tihy, Aurélie Hautefort, Brenda Kwak, Laura Rubbia-Brandt, Christian Toso

Background and aims

Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.

Methods

HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age.

Results

Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation.

Conclusions

The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.

Impact of an intervention program on drug adherence in patients with ulcerative colitis: Randomized clinical trial

by Mila Pacheco, Pedro Sá, Gláucia Santos, Ney Boa-Sorte, Kilma Domingues, Larissa Assis, Marina Silva, Ana Oliveira, Daniel Santos, Jamile Ferreira, Rosemeire Fernandes, Flora Fortes, Raquel Rocha, Genoile Santana

Aims

Evaluate the impact of an intervention program in non-adherent patients with ulcerative colitis.

Methods

Parallel controlled randomized clinical trial (1:1), approved by the ethics committee (No. 3.068.511/2018) and registered at The Brazilian Clinical Trials Registry (No. RBR-79dn4k). Non-adherent ulcerative colitis patients according to the Morisky-Green-Levine-test were included. Recruitment began in August 2019 until August 2020, with 6-month follow-up. All participants received standard usual care, and additionally the intervention group received educational (video, educational leaflet, verbal guidance) and behavioral interventions (therapeutic scheme, motivational and reminder type short message services). Researchers were blinded for allocation prior to data collection at Visits 1 and 2 (0 and 6 months). Primary outcome: 180-day adherence rate, with relative risk 95%CI. Secondary outcome: 180-day quality of life according to SF-36 domains, using Student’s t test. Variables with p Results

Forty-six and 49 participants were allocated in control and intervention groups, respectively. Two were excluded due to intervention refusal, and 4 and 6 were lost to follow-up in control and intervention groups. There was no post-intervention adherence rate difference, even after adjustment for type of non-adherence (unintentional/both/intentional) as confounder, or if considered as adherent the intervention group participants lost in follow-up. Interventions promoted better quality of life scores even after multivariate analysis for “Pain”, when adjusted for ulcerative colitis severity, sex, and marital status (β = 18.352, p = 0.004), “Vitality”, when adjusted for ulcerative colitis severity (β = 10.568, p = 0.015) and “Emotional Aspects”, when adjusted for disease severity, income, and education (β = 24.907, p = 0.041).

Conclusions

The intervention program was not able to produce a significant medication adherence rate difference between comparative groups, however, there was a significant improvement in quality of life. Study limitations may include: sample size calculated to identify differences of 30%, leading to a possible insufficient power; non blinded participants, exposing the results to the risk of performance bias; outcomes based on self-reported data.

Predictors of multidrug-resistant tuberculosis in a teaching hospital in Ghana: A case-control study

by Philomina Afful, Godwin Adjei Vechey, Peter Kipo Leta, Foster Bediako Gbafu, Fortress Yayra Aku

Multidrug-resistant Tuberculosis (MDR-TB) remains a global health concern. The disease results in a prolonged treatment and hence, poses a financial burden to affected individuals and their families. The Ghana National TB Control Programme (NTP) has made extensive efforts to control the menace, however, it remains a concern. This study, therefore, aimed to determine the predictors of multidrug-resistant TB in the Cape Coast Teaching Hospital of Ghana. An unmatched case-control study involving 37 cases and 111 controls was conducted using data of TB cases registered for treatment between January 2018 and December 2020 at the Cape Coast Teaching Hospital. Socio-demographic, individual level and social characteristics information were collected from respondents through telephone surveys, face-to-face interviews and review of records using a structured questionnaire built in the Kobo Collect Toolbox. The data was exported to Stata version 16.0 for analysis. Chi-square test and multiple logistic regression were used to determine the predictors of MDR-TB. Associations were considered statistically significant at a 95% confidence interval with a p-value of less than 0.05. The results revealed that the majority (25 [67.6%]) of MDR-TB cases and controls (76 [68.5%]) were aged 30 years and above with a median age of 36.5 (IQR: 28–50) years for all respondents, while 20 (54.1%) of MDR-TB cases and 33 (29.7%) of controls lived in households with one room residences for their families. The following predictors for MDR-TB were identified: BCG vaccination status (AOR = 0.17,95% CI:0.07–0.45), long distance to health facility (AOR = 4.11, 95% CI: 1.55–10.87), number of rooms in residence (AOR = 0.37,95% CI: 0.14–0.99) and first place of visit upon noticing TB symptom (AOR = 4.22,95% CI:1.31–13.64). Predictors of MDR-TB in the current study were multi-faceted. Measures to control MDR-TB should target socio-demographic, health-seeking behaviour and social-related concerns.

The burden of non-disabled frailty and its associated factors among older adults in Bangladesh

by Sabuj Kanti Mistry, A. R. M. Mehrab Ali, Uday Narayan Yadav, Saruna Ghimire, Afsana Anwar, Md. Nazmul Huda, Fouzia Khanam, Rashidul Alam Mahumud, Ateeb Ahmad Parray, Shovon Bhattacharjee, David Lim, Mark Fort Harris

Objective

The present study aims to measure the prevalence of non-disabled frailty and its associated factors among Bangladeshi older adults.

Methods

This cross-sectional study was conducted during September and October 2021 among 1,045 Bangladeshi older adults (≥60 years). Telephone interviews, using a semi-structured questionnaire, were undertaken to collect data on participants’ characteristics and level of frailty. The non-disabled frailty was measured using the ‘Frail Non-Disabled (FiND)’ questionnaire. A multinomial logistic regression model assessed the factors associated with frailty among the participants.

Results

Around a quarter of the participants (24.8%) were frail. The multinomial regression analysis showed that older participants aged ≥80 years (RRR = 3.23, 95% CI: 1.41–7.37) were more likely to be frail compared to participants aged 60–69 years. Likewise, the participants living in a large family with ≥4 members (RRR = 1.39, 95% CI: 1.01–1.92) were more likely to be frail compared to those living in smaller families. Also, participants having memory or concentration problems (RRR = 1.56, 95% CI: 1.12–2.17) were more likely to be frail compared to those who were not suffering from these problems. Moreover, participants whose family members were non-responsive to their day-to-day assistance (RRR = 1.47, 95% CI: 1.06–2.03) were more likely to be frail compared to those whose family members were responsive. Furthermore, participants who were feeling lonely (RRR = 1.45, 95% CI: 1.07–1.98) were more likely to be frail than their counterparts who were not feeling lonely.

Conclusions

The findings of the present study suggest developing tailored interventions to address the burden of frailty among the older populations in Bangladesh. In particular, providing long-term care and health promotion activities can be of value in preventing frailty and reducing adverse health outcomes among this vulnerable population group.