Hepatic steatosis and skeletal muscle alterations during the COVID-19 lockdown in a cohort of patients with chronic liver disease in Japan.

AIM: Following the coronavirus disease outbreak, a state of public emergency was declared worldwide, which enforced lifestyle changes. This study therefore aimed to investigate the changes in lifestyle, body composition, hepatic steatosis, and fibrosis in patients with chronic liver disease (CLD) under lockdown. METHODS: During the lockdown period, 1344 patients with CLD answered a lifestyle questionnaire. In 298 patients, body composition and liver stiffness measure (LSM)/controlled attenuation parameter (CAP) were analyzed by InBody and FibroScan, respectively, and serial data were obtained in 137 patients. RESULTS: More than half of the CLD patients answered decreases in physical activity and frequency of outings during lockdown, while diet was less affected. Overall, 58% of patients showed elevations in CAP values, which were not different statistically over time. Women, but not men, were more likely to increase CAP values during lockdown. Neither LSM nor serum fibrosis markers were elevated chronologically during lockdown. In men, body mass index (BMI), body fat percentage, and visceral fat area (VFA) were significantly increased, whereas in women, lower-limb muscle mass was significantly decreased. Patients with decreased SMI showed elevations in CAP and VFA values, and patients who exercised less showed increases in BMI. CONCLUSION: In response to lockdown, men tended to increase body fat but the degree of hepatic steatosis was less affected, while women were more likely to exacerbate hepatic steatosis with skeletal muscle loss among CLD patients. Gender-specific approaches need to be established for management of CLD patients to avoid exacerbation or comorbidity of steatotic liver disease.

Migration and risk of intellectual disability with and without autism: A population-based cohort study.

OBJECTIVE: To investigate whether parental migration, parental region of origin, timing of child's birth in relation to maternal migration and parental reason for migration are associated with intellectual disability (ID) with and without autism. METHODS: We used a register-based cohort of all individuals aged 0-17 years in Stockholm County during 2001-2011. General estimating equation logistic model and additionally sibling comparison were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The models were adjusted for child's sex and birth year and parental age at child's birth, and additionally for migrant-specific variables in the analyses including only children with migrant parent(s). RESULTS: Within the eligible sample of 670,098 individuals, 3781 (0.6%) had ID with autism, and 5076 (0.8%) had ID without autism. Compared with children with Swedish-born parents, children with both parents born abroad had an increased risk of ID with autism (OR = 1.6, CI 1.5-1.8) and ID without autism (OR = 1.9, CI 1.7-2.0). Among these children with both parents born abroad, it was protective of ID with autism when the child's birth occurred before and later than four years after maternal migration, which was replicated in the sibling comparison. The associations with both conditions were more pronounced with parental origin in regions comprising low- and middle-income countries and with reasons other than work or study. CONCLUSIONS: Parental migration is associated with ID regardless of co-occurrence of autism. Our results indicate an association between environmental factors during pregnancy related to migration and offspring ID with autism, although further confirmative studies are needed.

Migration or ethnic minority status and risk of autism spectrum disorders and intellectual disability: systematic review.

BACKGROUND: There is an emerging evidence that the migration and the ethnic minority status are associated with the risks of autism spectrum disorder (ASD) and intellectual disability (ID). This systematic review aimed to investigate whether associations are specific to ASD or ID; whether and which migration-related or ethnically determined factors are associated with the risk of ASD and ID; and what mechanisms may explain these risks. METHODS: A systematic literature search was conducted using Embase, Medline and PsycINFO for studies reporting on the risks of ASD and/or ID among migrants, descendants of migrants and/or ethnic minorities. Risks of any ASD, ASD + ID, ASD - ID and any ID were reviewed in relation to migration and ethnic minority status, with consideration to the study quality. In addition, possible underlying mechanisms suggested in the included studies were summarized. RESULTS: Thirty-five studies were included. The summarized evidence indicated an increased risk of ASD + ID and a decreased risk of ASD - ID in migrants, descendants of migrants and ethnic minorities. These associations appeared more pronounced among children of migrant mothers, with origin in low-income countries, and among descendants of migrants. Data on ID were scarce. Suggested mechanisms explaining the increased risks of ASD + ID included environmental factors acting in utero and genetic factors (including consanguinity), while ascertainment bias was proposed to account for the lowered risks of diagnosed ASD - ID. CONCLUSION: Migration-related factors acting in utero and/or associated with origin in low-income countries may be important in the ASD + ID aetiology, although further confirmative studies are needed.

L-carnitine prevents metabolic steatohepatitis in obese diabetic KK-Ay mice.

AIM: Pharmacological treatment for metabolic syndrome-related non-alcoholic steatohepatitis has not been established. We investigated the effect of L-carnitine, an essential substance for ß-oxidation, on metabolic steatohepatitis in mice. METHODS: Male KK-Ay mice were fed a high-fat diet (HFD) for 8 weeks, with supplementation of L-carnitine (1.25 mg/mL) in drinking water for the latter 4 weeks. RESULTS: Serum total carnitine levels were decreased following HFD feeding, whereas the levels were reversed almost completely by L-carnitine supplementation. In mice given L-carnitine, exacerbation of hepatic steatosis and hepatocyte apoptosis was markedly prevented even though HFD feeding was continued. Body weight gain, as well as hyperlipidemia, hyperglycemia, and hyperinsulinemia, following HFD feeding were also significantly prevented in mice given L-carnitine. High-fat diet feeding elevated hepatic expression levels of carnitine palmitoyltransferase 1A mRNA; however, production of ß-hydroxybutyrate in the liver was not affected by HFD alone. In contrast, L-carnitine treatment significantly increased hepatic ß-hydroxybutyrate contents in HFD-fed mice. L-carnitine also blunted HFD induction in sterol regulatory element binding protein-1c mRNA in the liver. Furthermore, L-carnitine inhibited HFD-induced serine phosphorylation of insulin receptor substrate-1 in the liver. L-carnitine decreased hepatic free fatty acid content in 1 week, with morphological improvement of swollen mitochondria in hepatocytes, and increases in hepatic adenosine 5'-triphosphate content. CONCLUSIONS: L-carnitine ameliorates steatohepatitis in KK-Ay mice fed an HFD, most likely through facilitating mitochondrial ß-oxidation, normalizing insulin signals, and inhibiting de novo lipogenesis in the liver. It is therefore postulated that supplementation of L-carnitine is a promising approach for prevention and treatment of metabolic syndrome-related non-alcoholic steatohepatitis.

Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by trans-fatty acid plus fructose.

Excess consumption of trans-fatty acid could increase the risk of non-alcoholic steatohepatitis (NASH); however, treatment targeting trans-fatty acid-induced NASH has not been examined. Here we focused on the influence of trans-fatty acid intake on endoplasmic reticulum (ER) stress in hepatocytes, so we investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA), on trans-fatty acid-caused steatohepatitis using diabetic KK-A(y) mice. Elaidic acid (EA, trans-fatty acid) alone did not cause definitive liver injury. In contrast, EA plus low-dose fructose induced extensive apoptosis in hepatocytes with severe fat accumulation. EA plus fructose significantly increased ER stress markers such as glucose-regulated protein 78 (GRP78), eukaryotic initiation factor 2α (eIF2α) and phosphorylated c-jun N-terminal kinase (JNK), while PBA significantly reduced this response. In vitro, EA promoted expression of GRP78 and phosphorylation of eIF2α in primary-cultured hepatocytes. EA also increased hepatocellular susceptibility to low-dose tert-butyl hydroperoxide. Treatment with PBA significantly reduced these responses. In conclusion, EA potentiates susceptibly to non-hazardous dose of fructose, and increases ER and oxidative stress. PBA improved steatohepatitis induced by EA plus fructose through amelioration of ER stress. Therefore, ER stress-targeted therapy using a chemical chaperone is a promising novel strategy for trans-fatty acid-induced steatohepatitis.

Carbohydrate-deficient transferrin is a sensitive marker of alcohol consumption in fatty liver disease.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is increasing globally. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential for assessing alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550). METHODS: A total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers, such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV), were assessed using multiple linear regression analyses. RESULTS: %CDT significantly increased with 3-4 drinks/day. The optimal cutoff value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; and area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cutoff value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; and AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia. CONCLUSIONS: %CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD.

Metastatic seminoma in the duodenum: diagnosis with endoscopy followed by successful treatment.

Seminomas rarely metastasize to the gastrointestinal tract. In general, these lesions metastasize to the lungs or retroperitoneal lymph nodes. A 34-year-old Japanese man who had undergone orchiectomy for seminoma two years earlier experienced shortness of breath and tarry stools. The patient presented at our hospital and was diagnosed with metastatic seminoma to the third portion of the duodenum on double balloon endoscopy. He was effectively treated with chemotherapy and continues to progress well, with no episodes of recurrence.