Targeted metabolomics reveals plasma short-chain fatty acids are associated with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Alterations in the production of short-chain fatty acids (SCFAs) may reflect disturbances in the gut microbiota and have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed plasma SCFAs in patients with MASLD and healthy controls. METHODS: Fasting venous blood samples were collected and eight SCFAs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Relative between-group differences in circulating SCFA concentrations were estimated by linear regression, and the relation between SCFA concentrations, MASLD, and fibrosis severity was investigated using logistic regression. RESULTS: The study includes 100 patients with MASLD (51% with mild/no fibrosis and 49% with significant fibrosis) and 50 healthy controls. Compared with healthy controls, MASLD patients had higher plasma concentrations of propionate (21.8%, 95% CI 3.33 to 43.6, p = 0.02), formate (21.9%, 95% CI 6.99 to 38.9, p = 0.003), valerate (35.7%, 95% CI 4.53 to 76.2, p = 0.02), and α-methylbutyrate (16.2%, 95% CI 3.66 to 30.3, p = 0.01) but lower plasma acetate concentrations (- 30.0%, 95% CI - 40.4 to - 17.9, p < 0.001). Among patients with MASLD, significant fibrosis was positively associated with propionate (p = 0.02), butyrate (p = 0.03), valerate (p = 0.03), and α-methylbutyrate (p = 0.02). Six of eight SCFAs were significantly increased in F4 fibrosis. CONCLUSIONS: In the present study, SCFAs were associated with MASLD and fibrosis severity, but further research is needed to elucidate the potential mechanisms underlying our observations and to assess the possible benefit of therapies modulating gut microbiota.

Referral Patterns for Patients with Nonalcoholic Fatty Liver Disease.

The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. This study evaluates the referral pattern of patients with NAFLD. A cohort study evaluating all patients with NAFLD referred to a single Gastroenterology Department from January 2017 to June 2020. Electronic patient referral letters were reviewed, and patients with NAFLD were diagnosed using standardized tests as part of a prospective cohort study. Predictors of nonalcoholic steatohepatitis (NASH) with significant (≥F2) fibrosis were evaluated in logistic regression analyses. In total, 323 (18.6%) of 1735 patients referred to the Gastro Unit during the study period were diagnosed with NAFLD. Patients were referred from general practitioners (62.5%) or other hospital departments (37.5%). Most referral letters included information suggesting a possible diagnosis of NAFLD (patient history, blood tests, or diagnostic imaging) or used the nonspecific general diagnosis suspected disease (Z.038). Out of 110 patients referred for a liver biopsy, 71 (22%) had NASH with significant fibrosis (F2 n = 39, F3 n = 19, F4 n = 13). Thirty-nine of these patients were referred from the primary sector. A logistic regression analysis (adjusted for age and gender) including all 323 patients showed that type 2 diabetes was the only significant independent predictor of NASH with fibrosis.

Henoch-Schönlein Purpura: A Literature Review.

Henoch-Schönlein purpura is the most common childhood vasculitis, but may also affect adults. This article reviews the literature since 2011 on advances in diagnosis, clinical disease manifestations, pathophysiology and treatment of Henoch-Schönlein purpura. The clinical manifestations are thought to arise from IgA depositions in blood vessel walls in the affected organs, mostly skin, gastrointestinal tract, joints and kidneys. Corticosteroids may be effective in rapid resolution of renal manifestations and treating joint and abdominal pain, but they are not proven effective for treating organ manifestations and complications, such as glomerulonephritis, bowel infarction or intussusception. Mycophenolate mofetil or cyclosporine A may be better treatment choices in case of renal involvement. Other immunosuppressive and immunomodulating drugs, such as rituximab and dapsone, are promising, but larger studies are needed to confirm these findings. Cancer screening should be considered in older males diagnosed with Henoch-Schönlein purpura.

The first Danish family reported with an AQP5 mutation presenting diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type, hyperhidrosis and frequent Corynebacterium infections: a case report.

BACKGROUND: An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, palmoplantar keratoderma of Bothnian type, is caused by mutations in the AQP5 gene encoding the cell-membrane water channel protein aquaporin 5 leading to defective epidermal-water-barrier function in the epidermis of the palms and soles. CASE PRESENTATION: We report the first Danish family diagnosed with diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type in which fourteen individuals are potentially affected. The proband, a 36-year-old male had since childhood been affected by pronounced hyperhidrosis of the palms and soles along with palmoplantar keratoderma. He reported a very distinctive feature of the disorder, aquagenic wrinkling, as he developed pronounced maceration of the skin with translucent white papules and a spongy appearance following exposure to water. The patient presented recurrent fungal infections, a wellknown feature of the condition, but also periodic worsening with pitted keratolysis and malodour due to bacterial infections. CONCLUSIONS: Palmoplantar keratoderma of Bothnian type, which may be associated with hyperhidrosis, is frequently complicated by fungal infections and may be complicated by Corynebacterium infections.