Gastrointestinal cancers in lean individuals with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Obesity and non-alcoholic fatty liver disease (NAFLD) are known risk factors for gastrointestinal (GI) cancers. However, GI carcinogenesis in lean NAFLD patients remains unclear. This systematic review and meta-analysis aims to investigate the association between lean NAFLD and GI cancer risk. METHODS: PubMed, Embase and Cochrane Library databases were systematically searched (from inception date to April 2023) for cohort studies assessing GI cancers in lean (body mass index [BMI] < 25 kg/m2 or < 23 kg/m2 in Asians) and non-lean (BMI ≥25 kg/m2 or ≥ 23 kg/m2 in Asians) NAFLD individuals. Data from eligible studies were extracted, and meta-analysis was carried out using a random effects model to obtain risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and sensitivity analyses were also performed. This study was registered in PROSPERO (CRD42023420902). RESULTS: Eight studies with 56,745 NAFLD individuals (11% were lean) and 704 cases of incident GI cancers were included. Lean NAFLD was associated with higher risk of hepatic (RR 1.77, 95% CI 1.15-2.73), pancreatic (RR 1.97, 95% CI 1.01-3.86) and colorectal cancers (RR 1.53, 95% CI 1.12-2.09), compared to non-lean NAFLD. No significant differences were observed for oesophagus, gastric, biliary and small intestine cancers. CONCLUSIONS: This study shows that lean NAFLD patients have an increased risk of liver, pancreatic and colorectal cancers compared to non-lean NAFLD patients, emphasizing the need to explore tailored cancer prevention strategies for this specific patient group. Further research is required to explore the mechanisms underlying the association between lean NAFLD and specific GI cancers.

Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.

Increased aortic stiffness in adults with chronic indeterminate Chagas disease.

An ever-increasing number of patients with chronic indeterminate Chagas disease are diagnosed with early vascular and cardiac abnormalities, as cardiovascular imaging becomes more sensitive. However, the currently available information on aortic stiffness (a prognostic marker for adverse cardiovascular outcomes) in these patients is scarce. In this study, we consecutively recruited 21 asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease and 14 Bolivian adults, who were seronegative for Trypanosoma cruzi infection. No participants had a prior history of heart disease, hypertension, diabetes, chronic kidney disease or atrial fibrillation. Carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), carotid intima-media thickness and conventional echocardiographic measurements were recorded in all participants. Patients with chronic indeterminate Chagas disease had significantly higher cf-PWV (7.9±1.3 vs. 6.4±1.1 m/s, p = 0.003) and greater HOMA-estimated insulin resistance than subjects without Chagas disease. The two groups did not significantly differ in terms of age, sex, smoking, adiposity measures, blood pressure, plasma lipids, fasting glucose levels as well as cr-PWV, carotid intima-media thickness measurements, left ventricular mass and function. Presence of chronic indeterminate Chagas disease was significantly associated with increasing cf-PWV values (ß coefficient: 1.31, 95% coefficient interval 0.44 to 2.18, p = 0.005), even after adjustment for age, sex, heart rate, systolic blood pressure and insulin resistance. In conclusion, asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease have an early and marked increase in aortic stiffness, as measured by cf-PWV, when compared to Bolivian adults who were seronegative for Trypanosoma cruzi infection.