The Correlation between the CT Liver Volume and the Actual Weight of the Resected Cirrhotic Liver in Transplantation Patients

Objective: Volumetric assessment with computed tomography (CT), known as CT volumetry, is the preferred method for estimating future liver remnant. However, the data regarding the usage of CT volumetry to estimate future liver remnant of the diseased liver is still lacking. This study was designed to evaluate the correlation between the liver volume, calculated by CT, and the actual weight of the resected liver in patients who underwent orthotopic liver transplantation.Material and Methods: A total of 32 patients having underwent liver transplantation; from March 2009 to June 2015, were included. A radiologist retrospectively reviewed the pre-operative CT and performed the volume measurement. Statistical analysis was performed to determine the relationship between the estimated liver volume and the actual liver weight.Results: The estimated liver volume was significantly different among the cirrhosis of different etiology (p-value=0.001 for the total liver volume and p-value=0.003 for the functional liver volume). Compared with the total liver volume, the functional liver volume had a stronger correlation with the actual weight of the resected liver (r=0.955 vs. r=0.786). The following formula can be used to accurately estimate the expected weight of the resected liver (expected liver weight: ELW), based on the estimated functional liver volume (FLV) derived by CT volumetry: ELW=489.531+(0.618*FLV). The R-squared for this regression model was 0.914.Conclusion: CT volumetry is reliable and accurate in predicting the actual amount of the resected liver parenchyma in cirrhotic patients.

Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats

Background Ischemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats. Methods Twenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1β, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization. Results The administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1β and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.

Metabolomics Identifies Serum Metabolites Different in Zambian Women with Adequate versus Deficient Total Liver Vitamin A Reserves Despite Adequate Serum Retinol Levels

Objectives Vitamin A deficiency (VAD) has remained a leading cause of morbidity and mortality throughout the world for decades, however there are still challenges defining VA status because the most common biomarker, serum retinol, is regulated homeostatically except in extreme deficiency and affected by inflammation; therefore, more accurate biomarkers to define VAD are needed. Furthermore, the effects of VAD on metabolism are still being uncovered. The objective was to investigate whether serum metabolomics profiles differed between Zambian women with adequate versus deficient VA status measured by the gold-standard biomarker total liver VA reserves (TLR) whose serum retinol concentrations did not differ. Methods Retinol isotope dilution (RID) was used to estimate TLR in Zambian women in the Rufunsa district; serum aliquots were selected for metabolomics based on adequate (TLR > 0.1–1 μmol VA/g liver) or deficient (TLR < 0.1 μmol/g) VA status (n = 10/group). Serum retinol levels were indicative of adequacy (>0.7 μmol/L) and were not different between groups. Serum samples were analyzed by LC-MS using four metabolomics assays. Metabolomics data were covariate-adjusted for age and BMI. Results Ten metabolites were different between the adequate and deficient vitamin A groups (P < 0.05). Metabolites lower in the deficient group included multiple phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs), as well as lipoxygenase (LOX)-derived oxylipins (9-HODE and 17-HDoHE), choline, and anthranilic acid. One cholestryl ester was elevated in the deficient group. Conclusions The study revealed numerous metabolites altered by RID-measured VAD and adequacy despite similarly adequate serum retinol levels in both groups. Future research is required to investigate the mechanisms by which phospholipids such as PCs and PEs, as well as LOX-derived oxylipins, are altered by VA status and the potential use of these metabolites as biomarkers of VAD. Funding Sources University of Wisconsin-Madison Global Health Institute visiting scholar fellowship (CK and SAT).

Perfluorooctanoic Acid Induces Liver and Serum Dyslipidemia in Humanized PPARα Mice Fed an American Diet

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPAR α)-expressing mice fed an American diet. Mice were exposed to PFOA (3.3 mg/l) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 μg/ml. In male and female hPPAR α mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of hPPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Across studies, a non-monotonic effect of PFOA on serum TG is evident, with the serum PFOA concentration in this study falling near the null point between increasing and decreasing serum TG. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

Disease burden of liver cancer attributable to specific etiologies in China from 1990 to 2019: An age-period-cohort analysis

Temporal trends of total liver cancer have been well reported in China, especially the trends caused by hepatitis B (HBV); however, the trends of liver cancer attributable to specific etiologies have rarely been reported in China. Thus, this study aims to describe the temporal trends in the incidence, mortality and DALYs of total and etiology-specific liver cancer in China from 1990 to 2019. We extracted the incidence, mortality and disability-adjusted life years (DALYs) of total and etiology-specific liver cancer in China from 1990 to 2019 from global disease burden (GBD) 2019. We plotted the trends in the age-standardized rates for incidence, mortality, and DALYs using locally weighted regression (LOESS)-smoothed data from 1990 to 2019. The age-standardized rate for the incidence of liver cancer was analyzed with an age-period-cohort method. The age-standardized rates for incidence, death, and DALYs decreased by −58.8%, −63.8%, and −65.6%, respectively, between 1990 and 2019. The age-standardized rates of incidence, mortality, and DALYs of total liver cancer showed similar temporal patterns, presenting an overall decline, with the average annual percentage change (AAPC) ranging from −3.3% to −3.8%. People in the period before 2007 had a higher risk, and people after 2007 had a lower risk. The cohort risk ratios (RRs) showed decreasing patterns, with the most rapid decline observed in the 1910 to 1960 cohorts. Our study generally revealed favorable decreasing trends for total and etiology-specific liver cancer in China from 1990 to 2019. Despite the overall decline in liver cancer due to heavy alcohol use and obesity from 1990 to 2019, there have been apparent upward trends since 2006. Planned population-wide interventions targeting heavy alcohol use and obesity may mitigate the increasing trends in liver cancer attributable to alcohol use and NASH.

Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves

Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs) for North Americans suggested that a minimally acceptable total liver vitamin A reserve (TLR) is 0.07 µmol/g, which is not explicitly expressed as a vitamin A deficiency cutoff. The Biomarkers of Nutrition for Development panel set the TLR cutoff for vitamin A deficiency at 0.1 µmol/g based on changes in biological response of several physiological parameters at or above this cutoff. The criteria used to formulate the DRIs include clinical ophthalmic signs of vitamin A deficiency, circulating plasma retinol concentrations, excretion of vitamin A metabolites in the bile, and long-term storage of vitamin A as protection against vitamin A deficiency during times of low dietary intake. This review examines the biological responses that occur as TLRs are depleted. In consideration of all of the DRI criteria, the review concludes that induced biliary excretion and long-term vitamin A storage do not occur until TLRs are >0.10 µmol/g. If long-term storage is to continue to be part of the DRI criteria, vitamin A deficiency should be set at a minimum cutoff of 0.10 µmol/g and should be set higher during times of enhanced requirements where TLRs can be rapidly depleted, such as during lactation or in areas with high infection burden. In population-based surveys, cutoffs are important when using biomarkers of micronutrient status to define the prevalence of deficiency and sufficiency to inform public health interventions. Considering the increasing use of quantitative biomarkers of vitamin A status that indirectly assess TLRs, i.e. the modified-relative-dose response and retinol-isotope dilution tests, setting a TLR as a vitamin A deficiency cutoff is important for users of these techniques to estimate vitamin A deficiency prevalence. Future researchers and policymakers may suggest that DRIs should be set with regard to optimal health and not merely to prevent a micronutrient deficiency.

A study on causes of cattle liver condemnation at an abattoir in Omdurman area, Khartoum State, Sudan

Background Information obtained from abattoirs on the causes of liver condemnation is important in preventing the spread of diseases and for promoting food security. The current study reviews three years (2009 to 2011) postmortem inspection records of cattle slaughtered at an abattoir in Omdurman, Khartoum State, Sudan. The aim was to determine the prevalence of diseases and conditions that lead to liver condemnation. Results From a total of 234,175 cattle slaughtered, 8,910 (3.8%) livers were condemned due to several diseases/conditions mainly fasciolosis, cysticercosis, necrosis, abscess, calcification, hemorrhages, liver cirrhosis, hydatidosis, and other miscellaneous causes. Collectively, fasciolosis was the leading cause of liver condemnation and was responsible for 51.6 % of total liver condemnations followed by necrosis (18.6%), and cysticercosis (13.5%). Conclusions Because of their zoonotic nature, the observed high frequency of some detected diseases/conditions is thought to pose a public health risk among consumers. This survey could be used as a regional baseline for future monitoring of control programmers against these liver diseases.

Risk Prediction of Radiation-Induced Hepatic Toxicity Complications in Patients With Hepatocellular Carcinoma

We use dose-volume factors to predict the risk of radiation-induced hepatic toxicity (RIHT) complications in patients with hepatocellular carcinoma (HCC) for controlling the low tolerance of liver organs to radiation and reducing the incidence of radiation-induced hepatic toxicity complications. This study retrospectively collected 114 patients who underwent Intensity Modulation Radiation Therapy (IMRT) for hepatocellular carcinoma between 2014 and 2017. The total number of patients was 69 after excluding normal liver organs whose volume did not reach 700 cc and extreme data. A total of 138 experimental samples were generated using the bootstrap method. All patients were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) during treatment to determine the degree of increase in blood draws and to judge for radiation-induced hepatic toxicity complications. The patient received dose-volume parameters were uniformly adjusted using a bioequivalent dose conversion of 2 Gy/fraction. The study data were divided into normal and total liver received dose-volume. Least absolute shrinkage and selection operator (LASSO) was used to select predictors and logistic regression (LR) was used to establish the performance model. LASSO was used to select the patient dose-volume parameter predictor. The risk factors of normal liver received dose-volume were age and NLV30 Gy. The risk factors of total liver received dose-volume were age and TLV35 Gy. For patients with hepatocellular carcinoma receiving radiation therapy (RT), this study recommends that a normal liver receiving a dose volume of 30 Gy should be less than 54.75%, so that the probability of RIHT can be less than 50%. A total liver receiving a dose volume of 35 Gy should be less than 54.75% so that the probability of RIHT can be less than 50%. It can control the low tolerance of liver organs to radiation and reduce the incidence of hepatotoxic complications induced by radiotherapy techniques.