Rising incidence,progression and changing patterns of liver disease in Wales 1999-2019

BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services.METHODS The registry is populated by International Classification of Diseases-10(ICD-10)code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019.Pseudo-anonymised linkage of:(1)Causative diagnoses;(2)Cirrhosis;(3)Portal hypertension;(4)Decompensation;and(5)Liver cancer diagnoses enabled tracking liver disease progression.RESULTS The population of Wales in 2019 was 3.1 million.Between 1999 and 201973054 individuals were diagnosed with a hepatic disorder,including 18633 diagnosed with cirrhosis,10965 with liver decompensation and 2316 with hepatocellular carcinoma(HCC).Over 21 years the incidence of liver diseases increased 3.6 fold,predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease(NAFLD);the leading cause of liver disease from 2014.The incidence of cirrhosis,decompensation,HCC,and allcause mortality tripled.Liver-related mortality doubled.Alcohol-related liver disease(ArLD),autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality.CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years.Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD.Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.

Effects of Insulin Treatment on Intracellular Lipid Metabolism in Liver of Diabetic Rats

The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin （25 mg/kg） and fat rich food. According to the results of oral glucose tolerance test （OGTT） and glucose-induced insulin secretion test （IRT）, the rats were divided into two groups： untreated group （UT） and insulin-treated group （IT）. Normal rats （NC） served as controls. The treatment with either Humulin N （4-6 U/kg every day）, or saline lasted for 4 weeks. Body weight, OGTT, IRT, blood lipids, intracellular lipids in liver, hepatic fatty acid oxidation and the activity of fatty acid synthase （FAS） were detected. The change of liver histology was observed. The insulin sensitivity index （ISI） was applied to assess the status of insulin resistance. The results showed that as compared with NC group, the plasma and hepatic intracellular Triglyceride （TG）, total cholesterol （TC） and free fatty acids （FFAs） were increased significantly in UT group （P〈0.05）, and lipid droplets could be seen dispersedly in the liver specimens, the hepatic fatty acid oxidation was increased markedly （P〈0.05）, while the fatty acid synthase activity decreased （P〈0.05）. Insulin treatment resulted in a further accumulation of lipids in liver by 55.7 %, 19.87 % and 22.2 % increase in TG, TC, FFAs respectively. The size of hepatocytes was enlarged and the cells were filled with fat drops. Plasma lipids showed little decrease and still significantly higher than those in NC group after the insulin treatment. Meanwhile, insulin treatment was companied by 20 % decrease in the rate of fatty acid oxidation and 31 % increase in hepatic FAS activity compared to, UT group. It was concluded that treatment with insulin on type 2 diabetic rat increases hepatic intracellular lipid accumulation by inhibiting hepatic fatty acid oxidation and activating FAS.

Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude

AIM:To use leptin-deficient(ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification(ASQ) mode and the associated analytical parameter,"focal disturbance ratio"(FD-ratio).METHODS:Nine ob/ob mice,at 5,8,and 12 wk of age(n = 3 in each age group),were used as models for hepatic steatosis.Echo signals obtained from ultrasonography in the mice were analyzed by ASQ,which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region.FD-ratio,as calculated from this analysis,was the focus of the present study.FD-ratio and fat droplet areas and sizes were compared between age groups.RESULTS:No fibrosis or inflammation was observed in any of the groups.The fat droplet area significantly(P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk.The median fat droplet size also significantly(P < 0.01) increased with age,from 1.33(0.55-10.52) m at 5 wk,2.82(0.61-44.13) m at 8 wk and 6.34(0.66-81.83) m at 12 wk.The mean FD-ratio was 0.42 ± 0.11 at 5 wk,0.11 ± 0.05 at 8 wk,and 0.03 ± 0.02 at 12 wk.The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk(P < 0.01).A significant negative correlation was observed between the FD-ratio and either the fat droplet area(r =-0.7211,P = 0.0017) or fat droplet size(r =-0.9811,P = 0.0052).CONCLUSION:This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis,and may serve as a quantitative biomarker of hepatic steatosis.

Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets

To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.

QUANTITATIVE ANALYSIS ON CHANGES OF HEPATIC HEMODYNAMICS AFTER TRANSCUTANEOUS ELECTRIC PULSE STIMULATION OF LOCAL POINTS BY USING COLOR DOPPLER ULTRASOUND DIAGNOSTIC APPARATUS

Objective: To evaluate the effect of transcutaneous electric pulse stimulation (TEPS) on hepatic blood flow and parenchymal microcirculation in patients with fatty liver. Methods: A total of 31 fatty liver volunteer patients were observed in this study. Changes of color Doppler energy (CDE) images before and after TEPS of local points nearby the liver were recorded by using color Doppler ultrasound diagnostic apparatus (ACUSON 128XP/10C). Sum of color pixel area (SCPA), average of color value (ACV) and SCPA×ACV (integral) of the hepatic flow images were analyzed by an image processing system, single blind method and paired t-test. Programmed TEPS (0.5- 150 Hz / 2 000 Hz , 10- 25 V ) was applied to the right Qimen (期门 LR 14)-Jingmen (京门 GB 25), Fuai (腹哀 SP 16)-Ganshu (肝俞 BL 18) respectively for 15 min. Results: Compared with basic values of pretreatment, SCPA, ACV and SCPA×ACV increased significantly (t=2.71, P<0.02; t=3.42, P<0.01; and t=8.15, P<0.001) after TEPS, meaning improvement of hepatic blood flow supply. Conclusion: TEPS of acupoints near the liver can improve hepatic blood flow and hepatic parenchymal microcirculation in patients with fatty liver.