MAFLD vs NAFLD: Much more than a letter change
Non-alcoholic fatty liver disease (NAFLD) is commonly associated with metabolic dysfunction, and there have been calls to change the name to metabolic associated fatty liver disease (MAFLD) to better reflect this. However, there have been questions about the interchangeability of the 2 terms, and significant controversy regarding the appropriate nomenclature. This systematic review and meta-analysis included 22 studies (nearly 380,000 patients, 19 studies based on imaging) assessing prevalence, risk factors, and outcomes of patients with MAFLD or NAFLD.
Overall MAFLD prevalence was 39.2%, and was highest in Europe (54.5%), followed by Asia (39.9%) and North America (29.1%). Patients had significantly higher odds of being diagnosed with MAFLD than NAFLD (OR 1.37, 95% CI 1.16-1.63), but this was apparent only in studies based on imaging, and not in those based on liver biopsy. Among 9,000 patient with MAFLD, 81.6% met diagnostic criteria for both MAFLD and NAFLD. In the comparisons of risk factors between MAFLD and NAFLD, there were no significant differences in age, hyperlipidemia, HgbA1c, or LDL. However, patients with MAFLD were more likely than those with NAFLD to be male, have higher BMI, lower HDL and higher triglyceride levels, and more likely to have hypertension and diabetes. In addition, MAFLD patients had higher levels of transaminases and NFS and FIB-4 fibrosis scores.
Comment: The debate may not be settled yet, but these findings show that a shift to a MAFLD definition could lead to missing one in five patients with NAFLD.
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Increased sympathetic tone mediates the relation between increased stress and UC flares
While the association between increased perceived stress and clinical flares in IBD is well-known, causality is less certain as there are few data regarding possible underlying physiological mechanisms. In this study, 110 individuals (mean age 37.5 years, 49% male) with UC in remission underwent morning salivary cortisol measurements, autonomic nervous system activity testing (heart rate variability and electrodermal activity) at baseline, and patient-reported Simple Colitis Clinical Activity Index (SCCAI) every 2 weeks. Clinical (SCCAI ≥ 5) and biochemical flares (SCCAI ≥ 5 with fecal calprotectin ≥ 250 μg/g) were assessed longitudinally.
Patients were clustered into high perceived and low perceived stress groups, based on measures of emotional lability, perceived ongoing stress, trait anxiety, and depression. Electrodermal activity (indicative of sympathetic activation) was significantly higher in the high stress group, but the other physiologic measures were comparable. During mean follow-up of 66 weeks, patients with high perceived stress were 3.6 times more likely to experience a clinical flare, but not a biochemical flare, compared to those with low stress. Changing the calprotectin cutoff to 150 μg/g did not alter the findings.
Comment: These findings open the possibility of additional therapeutic options for certain patients with IBD. For those with increased stress perception, interventions such as cognitive behavioral therapy could potentially decrease the risk of disease flares.
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Characterizing long GI COVID
Patients with COVID-19 infection can develop long-term gastrointestinal sequelae, but these have not been well-characterized in prospective studies. In this report, investigators recruited 320 patients who had been hospitalized with COVID-19 (mostly during the delta variant phase in India) and followed them for up to 6 months for the development of functional GI disorders (FGID) based on Rome IV criteria. There were 2 comparison groups: 320 healthy spouses or family members, and 280 healthy COVID-negative controls. None of the patients had prior history of COVID-19 or FGID based on Rome IV criteria.
Of the 320 cases, 27 (8.4%) had FGID at 3 months, and 21 (6.6%) at 6 months; the most common diagnoses were the irritable bowel syndrome, functional diarrhea, and functional dyspepsia. None of the control patients developed FGID for up to 6 months. Predictors of the development of FGID were severe COVID-19 and the presence of GI symptoms during the infection. The 27 patients with symptoms at 3 months underwent additional tests and 9 were positive: 8 had positive D-xylose tests indicating isolated carbohydrate malabsorption, one also had malabsorption syndrome, and one had intestinal methanogen overgrowth; however, intestinal biopsies at EGD were unrevealing in all 9.
Comment: Some patients who have recovered from COVID-19 can develop persistent FGID symptoms, and objective testing reveals abnormalities in about a third. Longer term follow-up data regarding natural history and outcomes are awaited.
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Which high-risk adenomas are highest risk?
High-risk adenomas (≥10mm, ≥25% villous component, high-grade dysplasia [HGD] or ≥3 non-advanced adenomas) are associated with increased risk of metachronous colorectal cancer (CRC). To better assess CRC risk based on individual HRA features, investigators conducted a systematic review and meta-analysis of 55 studies that included over 936,000 individuals (mean age 61 years, 60% male, mean follow-up 5.4 years).
Metachronous CRC risk was higher in adenomas ≥20mm vs 10-19mm (RR 2.08, 95%CI 1.20-3.61), HGD vs low-grade dysplasia (RR 2.89, 1.88-4.44), and villous vs tubular (RR 1.75, 1.33-2.31). However, multiplicity was not associated with significant differences in CRC risk, for ≥3 adenomas vs 1-2 (RR 1.24, 0.84-1.83) and for ≥5 adenomas vs 3-4 (RR 0.79, 0.30-2.11). When compared to normal colonoscopy, RR for adenoma ≥10mm was 2.61 (2.06-3.32), 6.62 (4.60-9.52) for HGD, 3.58 (2.24-5.73) for villous, and 2.03 (1.40-2.94) for ≥3 adenomas.
Comment: Size and HGD portend the highest risk of metachronous CRC, supporting current surveillance recommendations. The risk associated with multiplicity is less striking, indicating that patients with multiple non-advanced adenomas may not require as intensive surveillance as others in the HRA category-a finding that requires additional study.
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