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Background and Aims: The regulation of hepatic very-low-density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin-like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown., Approach and Results: Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal-mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL-TAG metabolism in PNPLA7-knockdown primary hepatocytes., Conclusion: PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE., (© 2020 by the American Association for the Study of Liver Diseases.)

Background and Aims: This study examined whether enhanced susceptibility of steatotic liver to ischemia-reperfusion (I/R) injury is due to impaired recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (LSECs, also called sinusoidal endothelial cell progenitor cells [sprocs]) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury., Approach and Results: Hepatic vessels were clamped for 1 hour in rats fed a high-fat, high-fructose (HFHF) diet for 5, 10, or 15 weeks. Matrix metalloproteinase 9 (MMP-9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver-selective MMP-9 inhibition. HFHF rats had mild, moderate, and severe steatosis, respectively, at 5, 10, and 15 weeks. I/R injury was enhanced in HFHF rats; this was accompanied by complete absence of hepatic vascular endothelial growth factor (VEGF)-stromal cell-derived factor 1 (sdf1) signaling, leading to lack of BM sproc recruitment. Liver-selective MMP-9 inhibition to protect against proteolytic cleavage of hepatic VEGF using either MMP-9 ASO or intraportal MMP inhibitor in 5-week and 10-week HFHF rats enhanced hepatic VEGF-sdf1 signaling, increased BM sproc recruitment, and reduced alanine aminotransferase (ALT) by 92% and 77% at 5 weeks and by 80% and 64% at 10 weeks of the HFHF diet, respectively. After I/R injury in 15-week HFHF rats, the MMP inhibitor reduced active MMP-9 expression by 97%, ameliorated histologic evidence of injury, and reduced ALT by 58%, which is comparable to control rats sustaining I/R injury. Rescue therapy with intraportal MMP inhibitor, given after ischemia, in the 5-week HFHF rat reduced ALT by 71% and reduced necrosis., Conclusions: Lack of signaling to recruit BM sprocs that repair injured LSECs renders steatotic liver more susceptible to I/R injury. Liver-selective MMP-9 inhibition enhances VEGF-sdf1 signaling and recruitment of BM sprocs, which markedly protects against I/R injury, even in severely steatotic rats., (© 2020 by the American Association for the Study of Liver Diseases.)

Some drugs may induce hepatotoxic lesions, such as steatosis or steatohepatitis found in Non-Alcoholic Fatty Liver Disease (NAFLD). Among these drugs there are some anti-tumoral molecules, such as methotrexate, 5-fluorouracil, irinotecan, tamoxifen and l-asparaginase. The hepatotoxic phenotype developed from treatment with such drugs is known as "CASH" for "Chemotherapy-induced Acute Steatohepatitis". The mechanism of toxicity is essentially based on mitochondrial toxicity. These lesions are chronic and often reversible when the treatment is stopped. Contributing factors related to the patient, the disease or the treatment play a major role in the emergence of CASH. It is important to identify chemotherapies with steatosis or steatohepatitis as risk factors in order to improve control of the metabolic risk factors associated with the patient and to reinforce monitoring during treatment. In the particular context of neo-adjuvant chemotherapy for metastatic colorectal cancer, a short duration of chemotherapy and a few-weeks delay between chemotherapy and surgery could reduce postoperative morbidity and mortality., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is now the most common etiology of chronic liver disease threatening global public health. However, the name "NAFLD" is no longer appropriate with the change of time. Recently, a new term, "metabolic dysfunction-associated fatty liver disease" has been proposed by an international panel of experts, which implies profound conceptual changes in terms of its metabolism-related etiology and disease heterogeneity. In this article we discuss the specific conceptual changes that clinicians, researchers and patients must absorb., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objectives: To assess clinically relevant difference in hepatic iron quantification using R2* relaxometry with (FS) and without (non-FS) fat saturation for the evaluation of patients with suspected hepatic iron overload., Methods: We prospectively enrolled 134 patients who underwent 1.5-T MRI R2* relaxometry with FS and non-FS gradient echo sequences (12 echoes, initial TE = 0.99 ms). Proton density fat fraction for the quantification of steatosis was assessed. Linear regression analyses and Bland-Altman plots including Lin's concordance correlation coefficient were performed for correlation of FS R2* with non-FS R2*. Patients were grouped into 4 severity classes of iron overload (EASL based), and agreement was evaluated by contingency tables and the proportion of overall agreement., Results: A total of 41.8% of patients showed hepatic iron overload; 67.9% had concomitant steatosis; and 58.2% revealed no iron overload of whom 60.3% had steatosis. The mean R2* value for all FS data was 102.86 1/s, for non-FS 108.16 1/s. Linear regression resulted in an R-squared value of 0.99 (p < 0.001); Bland-Altman plot showed a mean R2* difference of 5.26 1/s (SD 17.82). The concordance correlation coefficient was only slightly lower for patients with steatosis compared with non-steatosis (0.988 vs. 0.993). The overall agreement between FS and non-FS R2* measurements was 94.8% using either method to classify patients according to severity of iron storage. No correlation between R2* and proton density fat fraction was found for both methods., Conclusion: R2* relaxometry showed an excellent overall agreement between FS and non-FS acquisition. Both variants can therefore be used in daily routine. However, clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. We therefore recommend choosing a method and keeping it straight in the context of follow-up examinations., Key Points: • Both variants of R2* relaxometry (FS and non-FS) may be used in daily routine. • Clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. • It seems advisable choosing one method and keeping it straight in the context of follow-up examinations.

Animal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The prevalence and impact of hepatic steatosis among patients with autoimmune hepatitis (AIH) is not well described.We conducted a cross-sectional study to determine the prevalence of hepatic steatosis in AIH patients and examined its relationship with hepatic fibrosis using vibration controlled transient elastography. Liver stiffness measurement (LSM), controlled attenuation parameter (CAP), gender, current age, and body mass index (BMI) were collected from 277 AIH patients. Hepatic steatosis was defined as CAP >263 db/m.The study participants were mostly female (82%) with an average age of 49 years and BMI 29.7 kg/m. Mean LSM was 12.5 (standard deviation 13.5) kPa and CAP was 244 (standard deviation 63) db/m. The prevalence of coexisting steatosis was 33.2%, and steatosis did not correlate with LSM (r = 0.05, P = .46). In this study, only gender (females with 31% lower LSM on average compared to males, P = .001) and BMI (each unit increase of BMI resulted in a 1.48% increase on average LSM, P = .01) correlated with LSM. Male gender had significant association with increased LSM, after controlling for age, BMI, and CAP (P = .001).This exploratory study using noninvasive vibration controlled transient elastography revealed hepatic steatosis is highly prevalent in patients with AIH but not associated with liver fibrosis.

Background and Aims: Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults., Methods and Results: Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in "increase" group comparing with "no change" group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females., Conclusions: The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver., Competing Interests: Declaration of Competing Interest There is no potential conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of progressive liver pathologies, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. A liver biopsy is currently required to stratify high-risk patients, and predicting the degree of liver inflammation and fibrosis using non-invasive tests remains challenging. Here, we sought to develop a novel, cost-effective screening tool for NAFLD based on thermal imaging. We used a commercially available and non-invasive thermal camera and developed a new image processing algorithm to automatically predict disease status in a small animal model of fatty liver disease. To induce liver steatosis and inflammation, we fed C57/black female mice (8 weeks old) a methionine-choline deficient diet (MCD diet) for 6 weeks. We evaluated structural and functional liver changes by serial ultrasound studies, histopathological analysis, blood tests for liver enzymes and lipids, and measured liver inflammatory cell infiltration by flow cytometry. We developed an image processing algorithm that measures relative spatial thermal variation across the skin covering the liver. Thermal parameters including temperature variance, homogeneity levels and other textural features were fed as input to a t-SNE dimensionality reduction algorithm followed by k-means clustering. During weeks 3,4, and 5 of the experiment, our algorithm demonstrated a 100% detection rate and classified all mice correctly according to their disease status. Direct thermal imaging of the liver confirmed the presence of changes in surface thermography in diseased livers. We conclude that non-invasive thermal imaging combined with advanced image processing and machine learning-based analysis successfully correlates surface thermography with liver steatosis and inflammation in mice. Future development of this screening tool may improve our ability to study, diagnose and treat liver disease.

Objective: Hepatic steatosis has a high incidence in human immunodeficiency virus (HIV) infected people, and there is no effective non-invasive method to evaluate it. This study aims to evaluate the diagnostic value of non-invasive models for hepatic steatosis in this population. Methods: A single-center retrospective study was applied to evaluate: (1) the diagnostic value of controlled attenuation parameters (CAP) and hepatic steatosis index (HSI) in HIV-infected patients with hepatic steatosis; (2) the ability of the non-invasive model to distinguish hepatic steatosis caused by abnormal glucose and lipid metabolism and hepatic steatosis caused by hepatitis C virus infection; (3) the diagnostic value of the above models for hepatic steatosis in patients co-infected with HIV/hepatitis C virus. The diagnostic value of the model was analyzed and evaluated by diagnostic test and receiver operating characteristic curve. Results: (1) the diagnostic value of hepatic steatosis for HIV-infected patients: when CAP = 232 dB/m, the sensitivity and specificity were 89.2% and 78.1%, respectively; when HSI = 34, the sensitivity and specificity were 79.1% and 83.2%, respectively. (2) The ability to identify the causes of hepatic steatosis in HIV-infected patients: when CAP = 258dB/m, the sensitivity and specificity were 81.5% and 88.2%, respectively; when HSI = 37, the sensitivity and specificity were 70.7% and 92.4%, respectively. (3) The diagnostic value of hepatic steatosis in patients co-infected with HIV/hepatitis C virus: when CAP = 241 dB/m, the sensitivity and specificity were 80% and 71.4%, respectively; when HSI = 32, the sensitivity and specificity were 73% and 68.9%, respectively. Conclusion: CAP and HSI have superior diagnostic value for hepatic steatosis in patients infected with HIV.

Objectives: Our aim was to investigate the frequency of steatohepatitic morphology in hepatocellular adenoma (HCA) and correlate with its clinical parameters and risk factors underlying nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH)., Methods: We examined a series of 41 liver resection specimens diagnosed with HCA for steatohepatitic changes. Background nonneoplastic liver was also evaluated. Clinical records were reviewed for risk factors of NAFLD/NASH., Results: Six steatohepatitic HCAs (SH-HCAs) were identified, with an overall prevalence of six (14.6%) of 41, of which three were HNF1α inactivated and three were inflammatory, but none were β-catenin mutated. Five of the six patients with SH-HCA had at least one known risk factor for NAFLD/NASH, including obesity (n = 4; 66.7%), diabetes (n = 5; 83.3%), hypertension (n = 3; 50%), and dyslipidemia (n = 1; 16.7%). Compared with the patients without SH-HCA, the patients with SH-HCA had a higher frequency of type 2 diabetes, obesity, and hypertension. Of the six SH-HCAs, background nonneoplastic liver showed significant steatosis in three (50%) cases and steatohepatitic changes in one (16.7%) case., Conclusions: Approximately 15% of HCAs in our series demonstrated steatohepatitic changes. Lack of such morphology in β-catenin-mutated subtype suggests reassurance in this morphologic variant of HCA., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The role of machine perfusion (MP) in the evaluation of liver grafts with macrovesicular steatosis (MaS) remains ill-defined as only a limited number of studies has been reported. The objective of the current study was to provide a systematic review to evaluate the role of MP in the setting of MaS livers., Methods: A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Eligible articles published up to April 2019 were included using the MEDLINE, Scopus, and Google Scholar databases., Results: Among the 422 articles screened, only 16 papers met the inclusion criteria. A total of 54 cases of MP use before liver transplantation were included. Sixteen (29.6%) grafts were from donors after circulatory death. In 22 (40.7%) cases, hypothermic machine perfusion was performed. Normothermic machine perfusion was done in the remaining 32 (59.3%) cases. According to the histological results of the donor core biopsy, a MaS value < 30% was observed in 41 (75.9%) cases, whereas 13 (24.1%) patients had moderate-to-severe (≥ 30%) MaS. Following categorization of the pooled population according to the presence of moderate-to-severe (≥ 30%) MaS in the donor graft, no differences were noted in terms of post-transplant death or severe complications following MP. There was no correlation between the proportion of MaS in the donor graft relative to post-transplant peak ALT among patients treated with MP. Among the entire pooled cohort, there was also no correlation between MaS values and ALT peak (R = 0.13; P = 0.42)., Conclusions: MP appears to be feasible and safe in MaS livers. Experience to date has been very limited, and the benefit of MP remains not determined. Prospective studies will need to define better the potential effect of "defatting" drugs used during the perfusion process on MaS.

Purpose: To evaluate the efficacy of attenuation measurement function (ATT), a newly developed quantitative ultrasonography(US) method based on measurement of the attenuation coefficient, using unenhanced computerized tomography(CT) attenuation values as a reference standard, for the detection and measurement of hepatosteatosis., Material and Methods: A total of 98 patients were analyzed. The diagnostic ability of ATT was evaluated using receiver operating characteristic (ROC) curve analysis, and the correlation between liver attenuation index (LAI), the liver-to-spleen attenuation ratio (CT L/S ), liver attenuation value (CT L ), and ATT was determined., Results: ATT is negatively correlated with LAI (r = -0.571, p < 0.001), CT L/S (r = -0.532, p < 0.001), and mean CT L (r = -0.50, p < 0.001). A significant difference was found between ATT values of patients with different grades of hepatosteatosis (p < 0.001). A significant difference was found between ATT values of patients with LAI < -10 and LAI > -10, CT L  < 40 and CT L  > 40, and CT L/S  < 1 and CT L/S  > 1 (p < 0.001). An ATT ≥ 0.665 showed a sensitivity of 100% and a specificity of 90% in diagnosing moderate-severe steatosis. The corresponding area under the ROC curve(AUROC) was 0.935. The intraclass correlation coefficient for the interobserver variability of ATT was 0.907 (95% CI, 0.85-0.95)., Conclusion: In conclusion, ATT values for evaluation of hepatosteatosis was closely correlated with the degree of hepatosteatosis and liver fat content. It can be used as a noninvasive method in the diagnosis and follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A strong association between chronic hepatitis C (CHC) and hepatic steatosis has been reported. However, the influence of steatohepatitis on hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) elimination remains unclear., Aim: To evaluate the development of HCC after HCV cure using a new steatohepatitis-related biomarker., Methods: This cohort study analysed the prospective database of 290 CHC patients without a history of HCC who achieved HCV elimination by direct-acting antivirals. We calculated the FibroScan-aspartate aminotransferase (FAST) score 12 weeks after the end of treatment (pw12). The risk of HCC was analysed using the multivariable Cox proportional hazard model., Results: HCV genotype (GT)1 was most prevalent at 72.4%, followed by GT2 (26.6%). Median follow-up period was 4.2 years (IQR 3.1-4.5). The cumulative HCC incidence for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35 (log-rank test: P < 0.001). The annual HCC incidence rate for a FAST score ≥ 0.35 was significantly higher than that for a FAST score < 0.35, in patients with liver stiffness measurement (LSM) ≥10 kPa (adjusted hazard ratio [HR] 4.41, 95% confidence interval [CI] 1.30-15.0, P = 0.018). After adjusting for variables, including age, albumin, alpha-fetoprotein, the patatin-like phospholipase domain-containing the 3 (PNPLA3) rs738409 genotype, and pw12 fibrosis markers with FIB-4, non-alcoholic fatty liver disease fibrosis score, and LSM, FAST score ≥ 0.35 was associated with the development of HCC (adjusted HR 4.42, 95% CI 1.02-19.9, P = 0.043)., Conclusions: Steatohepatitis-related biomarkers with the FAST score are helpful for predicting the development of HCC after HCV elimination., (© 2020 John Wiley & Sons Ltd.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The National Lung Screening Trial (NLST) demonstrated that annual screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. Nonetheless, the leading cause of mortality in the study was from cardiovascular diseases., Purpose: To determine whether the used machine learning automatic algorithms assessing coronary calcium score (CCS), level of liver steatosis and emphysema percentage in the lungs are good predictors of cardiovascular disease (CVD) mortality and incidence when applied on low dose CT scans., Materials and Methods: Three fully automated machine learning algorithms were used to assess CCS, level of liver steatosis and emphysema percentage in the lung. The algorithms were used on low-dose computed tomography scans acquired from 12,332 participants in NLST., Results: In a multivariate analysis, association between the three algorithm scores and CVD mortality have shown an OR of 1.72 (p = 0.003), 2.62 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively, and an OR of 1.12 (p = 0.044) for level of liver steatosis. Similar results were shown for the incidence of CVD, OR of 1.96 (p < 0.0001), 4.94 (p < 0.0001) for CCS scores of 101-400 and above 400 respectively. Also, emphysema percentage demonstrated an OR of 0.89 (p < 0.0001). Similar results are shown for univariate analyses of the algorithms., Conclusion: The three automated machine learning algorithms could help physicians to assess the incidence and risk of CVD mortality in this specific population. Application of these algorithms to existing LDCT scans can provide valuable health care information and assist in future research., Competing Interests: EE, RS, DC, OBA, and MO are employed by Zebra Medical Vision, a commercial entity. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background/aims: Lipodystrophy is a rare metabolic disorder characterized by near total or partial lack of subcutaneous adipose tissue and associated with insulin resistance. We aimed to evaluate the efficacy of magnetic resonance spectroscopy imaging (MRS) to explore the fat content of the liver in patients with lipodystrophy and to determine the relationship between the liver fat accumulation and clinical presentations of lipodystrophy., Materials and Methods: Between July 2014 and February 2016, 34 patients with lipodystrophy were assessed by MRS for quantification of hepatic steatosis. All patients had metabolic abnormalities associated with insulin resistance. Metabolic parameters and the MRS findings were analyzed to identify potential correlations between the liver fat content and disease severity., Results: The MRS fat ratios (MRS-FR) were markedly higher, indicating severe hepatic steatosis in lipodystrophy. Patients with generalized and partial lipodystrophy had comparable levels of MRS-FRs, although patients with generalized lipodystrophy were significantly younger. Patients with genetically based lipodystrophy had elevated MRS-FR compared to those with acquired lipodystrophy (p=0.042). The MRS-FR was positively correlated with liver enzyme alanine aminotransferase (p=0.028) and serum adiponectin (p=0.043)., Conclusion: Our data suggest that MRS might be an effective, noninvasive imaging method to quantify hepatic fat content in patients with lipodystrophy. Further studies are needed to validate the technique and threshold values which would allow accurate comparison of data acquired by different machines and centers.

Background: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts., Methods: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression., Results: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers., Conclusions: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Background: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer., Methods: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted)., Results: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03)., Conclusions: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Nonalcoholic fatty liver disease (NAFLD) affects at least 25% of the general adult population worldwide. Because only a fraction of the patients would develop liver-related complications, it is preferable to perform non-invasive tests as the initial assessment. This review summarizes the known and potential confounding factors that affect the performance of non-invasive tests of hepatic steatosis and fibrosis in patients with NAFLD. Clinicians may apply the knowledge and exercise caution in selecting investigations and interpreting test results when confounding factors are present.

Background: Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer., Methods: This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group., Results: Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients., Conclusions: Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time., Competing Interests: The authors have declared that no competing interests exist.

Our data about pathogenesis of hepatic steatosis after liver transplantation is scarce. This study aimed to investigate the association between serum adipokines and insulin resistance with hepatic steatosis in liver transplant recipients. We investigated the association between insulin resistance, serum adiponectin, insulin, and leptin with hepatic steatosis in a cohort of liver transplant recipients. Homeostatic model assessment of insulin resistance 2 (HOMA 2-IR) was used for estimation of insulin resistance. Hepatic steatosis was determined using ultrasound and controlled attenuation parameter (CAP). A total of 178 patients were included. 79 patients (44.4%) had hepatic steatosis. Serum adiponectin (OR: 0.912; 95% CI 0.869-0.957; P < 0.001), serum leptin (OR: 1.060; 95% CI 1.017-1.102; P = 0.005), HOMA2-IR (OR: 1.671; 95% CI 1.049-2.662; P = 0.031), and post-transplant diabetes mellitus (PTDM) (OR: 5.988; 95% CI 1.680-21.276; P = 0.006) were independently associated with hepatic steatosis after liver transplantation. CAP values were negatively correlated with serum adiponectin (P = 0.011) and positively correlated with serum insulin (P = 0.001), leptin (P < 0.001) and HOMA2-IR (P < 0.001). Insulin resistance and alterations in adipokines might have central role in pathogenesis of hepatic steatosis after liver transplantation and can be targeted for diagnostic and therapeutic purposes.

(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD ( n = 12), patients with IFALD steatosis ( n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis ( p = 0.032), Aspartate transaminase-to-Platelet Ratio Index ( p < 0.001), Fibrosis-4 Index ( p = 0.010), Forns Index ( p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index ( p = 0.002) and Fibrosis Index ( p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.

Rationale: Acute fatty liver of pregnancy (AFLP) is extremely hazardous to pregnant woman in the 3rd trimester of pregnancy. AFLP has an insidious onset and nonspecific experimental indicators, which therefore is difficult to be diagnosed., Patient Concerns: Case 1 was transferred to our hospital for hypertensive disorders complicating pregnancy at gestation of 38 weeks + 3 days. Case 2 was transferred to our hospital for suspicious fetal heart monitoring response at gestation of 36 weeks + 4 days. Case 3 was transferred to our hospital for prelabor rupture of membranes at gestation of 37 weeks + 1 days., Diagnosis: The diagnosis of AFLP was based on the Swansea criteria., Interventions: All 3 cases were delivered by cesarean section, and they were all transferred to intensive care unit for further treatment. Cases 2 and 3 were subjected to plasma exchange and continuous renal replacement therapy., Outcomes: In this study, all 3 patients were initially diagnosed as gastritis. In addition, case 1 was diagnosed as preeclampsia and her AFLP was misdiagnosed with postpartum hemorrhage after cesarean delivery. Case 2 was admitted to the hospital for intrahepatic cholestasis of pregnancy and fetal distress, but we considered it as AFLP before delivery. Case 3 was treated according to severe intrahepatic cholestasis of pregnancy, but we rediagnosed it as postpartum hemorrhage and disseminated intravascular coagulation after cesarean delivery. Neonatal asphyxia and complications were not found. All of the 3 cases were fully recovered and discharged from our hospital., Lessons: If there are multiple risk factors including vomiting, abdominal pain, and fetal distress, AFLP should be highly suspected. Early diagnosis, especially before termination of pregnancy, is the key to successful treatment of AFLP.

The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, "positive criteria" to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Patients with primary aldosteronism (PA) are complicated by metabolic syndrome more frequently than those without PA. Hyperaldosteronism has been reported to be associated with a higher prevalence of non-alcoholic fatty liver disease (NAFLD). We aimed to clarify the risk factors for hepatic steatosis in the two subtypes of PA, comparing the status of hepatic steatosis in each of these subtypes. This was a retrospective observational study. We enrolled patients with an aldosterone producing adenoma (APA) (n = 33) or idiopathic hyperaldosteronism (IHA) (n = 56). Hepatic fat content was evaluated using the ratio of liver to spleen (L/S) X-ray attenuation on unenhanced computed tomography. L/S ratio <1.0 was utilized for assessing as hepatic steatosis. Age, sex distribution, visceral fat percentage (VF%), and visceral fat area (VFA) did not differ between patients with the two PA subtypes. The percentages of patients with L/S ratio <1.0 was not different between the two subtypes (APA: 21.2 % (7/33) vs. IHA: 19.6 % (11/56), p = 1.00). In both subtypes, the L/S ratio negatively correlated with VF% (APA: r = -0.66, p < 0.001; IHA: r = -0.66, p < 0.001) and with VFA (APA: r = -0.44, p < 0.01; IHA: r = -0.37, p < 0.01). The status of hepatic steatosis, evaluated using L/S ratio, did not differ between patients with APA or IHA. Hepatic steatosis was affected by the amount of visceral fat.

Nonalcoholic Fatty Liver Disease (NAFLD) is a common cause of chronic liver disease in childhood and strongly associated with obesity. Routine biochemical non-invasive tests remain with low accuracy for diagnosis of NAFLD. We performed a cross-sectional study to examine potential associations between anthropometric and biochemical parameters, specially TGF-β, a prognosis marker for hepatic steatosis (HS). Between May and October 2019, seventy-two overweight adolescents were enrolled, of which 36 had hepatic steatosis. Hepatic, lipidic and glycemic profiles, and levels of vitamin D, ferritin and TGF-β were analyzed. Hierarchical cluster and a discriminant model using canonical correlations were employed to depict the overall expression profile of biochemical markers and the biochemical degree of perturbation. Median values of alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), and TGF-β were higher in the adolescents with HS. Values of body mass index (BMI)/age and ALT, but not of TGF-β, were gradually increased proportionally to augmentation of steatosis severity. In a multivariate analysis, TGF-β plasma concentrations were associated with occurrence of hepatic steatosis independent of other covariates. Discriminant analysis confirmed that TGF-β concentrations can identify HS cases. Our data reveal that HS patients exhibit a distinct biosignature of biochemical parameters and imply TGF-β as an important biomarker to evaluate risk of steatosis development., Competing Interests: The authors declare no conflict of interest.

Background: Our aim was to evaluate liver transplant outcomes involving donors with high macrosteatosis grafts in the obese modern liver transplant recipient population., Methods: A high-steatosis graft was defined as donor graft macrosteatosis ≥30% on biopsy. Recipient obesity was defined as body mass index (BMI) >35 adjusted for ascites. Raw and adjusted recipient liver transplant survival were evaluated and compared between 4 cohorts: (1) high-steatosis graft in high-BMI recipient; (2) low-steatosis graft in high-BMI recipient; (3) high-steatosis graft in normal-BMI recipient; and (4) low-steatosis graft in normal-BMI recipient., Results: After adjustment for multiple factors, recipient high-BMI remained an independent predictor of posttransplant mortality at 30 days (P < 0.0001) and persisted at 1 year (P = 0.009). A high-steatosis graft was the strongest independent predictor of mortality at 30 days (hazard ratio 2.05, 1.66-2.53; P < 0.0001) and that effect was diminished but persistent at 1 year (1.27, 1.10-1.46; P = 0.001)., Conclusions: Recipient high-BMI and a high-steatosis graft are both significant independent and equally powerful predictors of mortality after modern liver transplant. High-steatosis grafts transplanted into obese recipients have the highest mortality. The increase in mortality associated with a high-steatosis graft into a normal-BMI recipient is similar in magnitude to a low-steatosis graft placed into a high-BMI recipient.

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, which usually arises in cirrhotic liver. When the typical enhancement pattern, consisting of late arterial hyperenhancement followed by washout, is present in nodules larger than 1 cm, HCC can be confidently diagnosed without the need for tissue biopsy. Nevertheless, HCC can display an atypical enhancement pattern, either as iso or hypovascular lesion, or hypervascular lesion without washout. Not only the enhancement pattern of HCC could be atypical, but also a variety of histological types of HCC, such as steatotic, scirrhous, fibrolamellar, or combined hepatocellular-cholangiocellular carcinoma could raise diagnostic dilemmas. In addition, distinct morphological types of HCC or different growth pattern can occur. Awareness of these atypical and rare HCC presentations on magnetic resonance imaging is important for accurate differentiation from other focal liver lesions and timely diagnosis, which allows optimal treatment of patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background/aims: The aim of our study was to evaluate the diagnostic accuracy of B-Mode ultrasound and Hepatorenal Index (HRI) by high-end devices for the detection and classification of hepatic steatosis in patients with various causes of chronic liver disease (CLD)., Methods: We retrospectively enrolled patients with CLD who underwent liver biopsy and baseline ultrasound between March 2016 and May 2019. Sonographic graduation of steatosis (0°-III°) using B-Mode criteria and HRI were correlated with the histological graduation (S0 (<5% fat), S1 (≥5-33%), S2 (>33-66%) and S3 (>66%). Interobserver agreement was calculated., Results: 157 patients were evaluated. B-Mode ultrasound had a sensitivity of 75.6% and a specificity of 76.0% to differentiate between steatosis and no steatosis (AUROC 0.758). Using B-Mode criteria for advanced steatosis (≥II°), specificity for presence of histological steatosis was ≥98.7%. For detection of advanced steatosis (≥S2), sensitivity of B-mode criteria was 90.9%. In a subgroup of patients with advanced liver fibrosis, sensitivity of B-mode criteria was 95.0% for detection of advanced steatosis (S≥2). A HRI cut-off-value of 1.46 differentiates between patients with steatosis and patients without steatosis with a sensitivity of 42.7% and a specificity of 90.7% (AUROC 0.680). Interobserver agreement of both B-Mode and HRI was good to excellent., Conclusion: B-Mode ultrasound using high-end devices is an excellent method to detect advanced steatosis in patients with various CLD. For diagnosis of mild steatosis, modern ultrasound devices may have higher sensitivity but at the expense of specificity. Stage of fibrosis and etiology of CLD seem not to impact on diagnostic accuracy. The additional calculation of HRI seems to have no additional benefit with regard to detect or grade hepatic steatosis in our study population., Competing Interests: The authors have declared that no competing interests exist.

The correlation between hepatitis B virus (HBV) infection and metabolic syndrome (MetS) remains to be clarified. In this study, we explored this association in a large population in Southwest China. This was a cross-sectional study, with pooled adult health data. Multivariate logistic regression analysis, controlling for age, sex, HBV status, alanine aminotransferase, and fatty liver, was used to identify predictor(s) of MetS. Of the 96,175 participants, positive HBV was identified in 7984 (8.30%) and MetS in 12,092 (12.57%). The MetS prevalence was lower among HBV positive than negative individuals (11.64% versus 12.66%, P < 0.001). The adjusted odds (aOR) of positive HBV among individuals with MetS was 0.841 (95% confidence interval (CI), 0.771-0.916) in men and 0.834 (95% CI, 0.672-0.925) in women. Elevated triglyceride level, a component of MetS, was inversely associated with HBV status in both men and women: aOR, 0.551 (95% CI, 0.514-0.590) and 0.683 (95% CI, 0.605-0.769), respectively. Among HBV positive individuals, liver cirrhosis was more common among those with than without MetS (4.83% versus 2.93%, respectively; P = 0.002). HBsAg-seropositive are inversely associated with MetS, especially elevated triglycerides. Liver cirrhosis was more common among HBV infection patients with MetS.

Objectives: To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis., Methods: One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S0 < 5%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S3 > 66%); liver fibrosis was graded from F0 to F4. The correlation between AC and steatosis on pathology (%) was calculated using the Pearson correlation coefficient. The Student t or Mann-Whitney U test was used to compare continuous variables and ROC curve analysis was used to assess diagnostic performance of AC in diagnosing steatosis., Results: Overall, 43 (42%), 35 (35%), 12 (12%), and 11 (11%) patients were classified as S0, S1, S2, and S3, respectively. The AC was positively correlated with steatosis as a continuous variable (%) on pathology (r = 0.58, p < 0.01). Patients with steatosis of any grade had a higher AC than those without steatosis (mean 0.77 ± 0.13 vs. 0.63 ± 0.09 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.805). Patients with S2-S3 had a higher AC than patients with S0-1 (0.85 ± 0.11 vs. 0.67 ± 0.11 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.892). AC > 0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively, for diagnosing any grade of steatosis (S1-S3), and AC > 0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively, for diagnosing S2-S3. The presence of advanced fibrosis (F3-F4) did not affect the calculated AC., Conclusions: The attenuation imaging coefficient is a promising quantitative technique for the non-invasive diagnosis and quantification of hepatic steatosis., Key Points: • Measurement of the attenuation coefficient is achieved with a very high rate of technical success. • We found a significant positive correlation between the attenuation coefficient and the grade of steatosis on pathology. • The attenuation imaging coefficient is a promising quantitative technique for the noninvasive diagnosis and quantification of hepatic steatosis.

Background: Early diagnosis is important to lower the mortality rate of acute fatty liver of pregnancy (AFLP). The Swansea criteria is commonly used to diagnose AFLP, but some terms could only be reached when symptoms and signs have progressed, or are not efficient in clinical practice. Therefore, it is necessary to select cost effective tests to simplify and facilitate early suspicion of acute fatty liver of pregnancy., Methods: This is a retrospective study of 28,800 medical records at the Second Xiangya Hospital from 2009 to 2015, including 41 patients with AFLP and 172 other diseases that could show similar symptoms to AFLP. The evaluated variables included past history of liver diseases, blood pressure, gastrointestinal symptoms, blood count, liver function test, coagulation function test and blood sugar test. The sensitivity, specificity, positive predict value and negative predict value were calculated for models in diagnosing AFLP., Results: The significant variables associated with AFLP included gastrointestinal symptoms, blood pressure > 140/90 mmHg, aminotransferase> 42 IU/l, total bilirubin> 0.8 mg/dl, total bilirubin acid> 10.0 μmol/L, activated partial prothrombin time(APTT) > 34 s, prothrombin time(PT) > 14 s, white blood cells> 11 *10 6 /l and blood sugar< 72 mg/dl. Gastrointestinal symptoms +aminotransferase +bilirubin +bile acid +APTT/PT showed 97.6% sensitivity and 97.1% specificity to diagnose AFLP. Adding blood pressure, blood sugar or white blood cells decreased the accuracy of the statistical model., Conclusions: Application of a statistical model including maternal symptoms, biochemical and haematological parameters has high diagnostic accuracy for earlier identification of AFLP. However, this finding needs to be tested in another cohort to determine whether this statistical model has the same performance.

Our primary objective was to assess the independent association between liver fibrosis (LF) and abdominal fat accumulation (AFA) and fatty liver disease (FLD). We also aimed to determine the diagnostic accuracy of AFA and FLD for the prediction of cirrhosis measured using unenhanced low-dose computed tomography (CT). This is a cross-sectional study in stable human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with active HCV replication. CT was used to quantify fat content in segments III and VI of the liver and AFA. Transient elastometry was used to stage LF. Multivariate logistic regression, receiver operating characteristic curve analysis, and linear mixed model analysis were applied. One hundred fifteen HIV/HCV-coinfected patients were included. Cirrhosis was detected in 20.8% (24 patients). There was a high correlation between anthropometric characteristics and radiological variables. The factors independently associated with cirrhosis were albumin concentration [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.58-0.83; p  < .0001] and visceral fat accumulation (OR, 1.02; 95% CI, 1.01-1.04; p  = .0003). Multinomial analysis showed that visceral fat area (VFA) was the factor independently associated with stage F2 (OR, 1.02; 95% CI, 1.0-1.03; p  < .005) and albumin concentration with stage F3 (OR, 0.75; 95% CI, 0.64-0.89; p  < .001). VFA was the only radiological variable with an area under the curve >0.7 for the prediction of cirrhosis. There was no inter- or intraobserver variability in the measurement of AFA; however, high interobserver variability was recorded in the measurement of FLD. The association of VFA with cirrhosis, the high reproducibility of CT for the measurement of VFA, and the ability of VFA to predict cirrhosis make CT a suitable technique for identifying HIV/HCV-coinfected patients for closer surveillance.

Acute fatty liver of pregnancy (AFLP) is a rare, but potentially fatal condition, characterized by hepatic failure typically in the third trimester of pregnancy that is associated with multiorgan involvement resulting in a number of clinical and laboratory abnormalities. The cornerstone of management of AFLP includes prompt recognition, preparation for delivery, and supportive care such as reversal of coagulopathy. Early diagnosis, prompted delivery, and supportive care have resulted in improved maternal morbidity and mortality. This review focuses on the epidemiology, etiology, clinical presentation, diagnosis, management, and resolution of AFLP.

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G protein-coupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver.

Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn error of fat metabolism. In late-onset MADD, hepatopathy in the form of steatosis is commonplace and considered a benign and stable condition that does not progress to more advanced stages of liver disease, however, progression to cirrhosis and acute liver failure (ALF) has been reported in two previous case reports. Here, we report a 22-year-old man, who suffered from late-onset MADD and died from cirrhosis and ALF. In the span of three months repeated clinical examinations, blood tests, and diagnostic imaging as well as liver biopsy revealed rapid progression of hepatopathy from steatosis to decompensated cirrhosis with portal hypertension. Routine studies for recognized etiologies found no evident cause besides MADD. This case report supports the findings of the two previous case reports and adds further evidence to the suggestion that late-onset MADD should be considered a rare cause of cirrhosis and ALF., (©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy.)

Background: The association of thyrotropin (TSH) with overall (body mass index, BMI), visceral (waist circumference and steatosis), and upper subcutaneous (neck circumference, NC) adiposity markers is still controversial, and the aim of this study is to assess these associations in the baseline data of a large cohort from ELSA-Brasil., Methods and Findings: This cross-sectional study included 11,224 participants with normal thyroid function (normal TSH levels). BMI, waist circumference, NC and steatosis, defined by hepatic attenuation (mild or moderate/severe) were the explicative variables. TSH levels were log transformed (logTSH), and multivariate linear regression models were generated to estimate the associations between logTSH and BMI (continuous and categorized), waist circumference, NC, and steatosis after adjusting for sociodemographic characteristics, health behaviors, and comorbidities. The mean age was 51.5±8.9 years, 5,793 (51.6%) participants were women, 21.8% (n = 2,444) were obese, and 15.1% of the sample was TPOAb positive. The TSH levels were significantly higher in the obese group than in the reference group (<25.0 kg/m2). In the multivariable linear regression models, significant associations of logTSH with BMI and obesity were found. LogTSH was associated with waist circumference only among women. NC and steatosis were not related to TSH levels., Conclusions: TSH levels were associated with overall adiposity and obesity. Further studies may elucidate reference levels of TSH according to BMI status., Competing Interests: The authors have declared that no competing interests exist.

Secondary causes of fatty liver disease are important to recognize since specific therapy options are available for some of these causes. Common causes of secondary fatty liver disease comprise hepatitis C virus infection (HCV), endocrinological diseases, nutritional and intestinal diseases as well as genetic liver and metabolic diseases. Certain drugs may also predispose to the development of fatty liver disease. Primary fatty liver disease, also known as non-alcoholic fatty liver disease (NAFLD) is defined by the presence of steatosis hepatis without relevant alcohol consumption or other causes of secondary fatty liver disease. NAFLD occurs more frequently in patients with metabolic syndrome and thus can be seen as the hepatic manifestation of the metabolic syndrome.Therefore, presence of features of the metabolic syndrome should be assessed in all patients with fatty liver disease. Furthermore, alcohol consumption should be determined to rule out alcoholic liver disease (ASH). Further diagnostic work up for secondary causes of fatty liver disease should include screening for HCV infection, for hypothyroidism and for drugs associated with steatosis development. In a next step screening for Wilson's disease, hemochromatosis, celiac disease and lipid metabolism disorders should be performed. An extended endocrinological workup and a liver biopsy should be considered if the etiology of fatty liver disease remains unclear.Common genetic polymorphisms have been identified in several genes, such as PNPLA3, TM6SF2 and MBOAT7, which may promote the development and the progression of fatty liver disease irrespective of the underlying etiology (e. g. metabolic syndrome, ASH or HCV). The risk variants in these genes have additive effects on steatosis development and diseases progression towards fibrosis and cirrhosis. The diagnosis of secondary causes of fatty liver disease may allow for therapeutic intervention and prevent disease progression. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of NAFLD patients., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction : Fatty liver is rather common in pregnancy, occurring in two totally different conditions, i.e. nonalcoholic fatty liver disease (NAFLD) in pregnancy and acute fatty liver of pregnancy (AFLP). The former is a common condition, resulting by chance association because of the epidemics of obesity and the older age of many pregnant women in Western countries; the latter is a rare disease whose pathophysiology is still incompletely understood. Areas covered : We reviewed the evidence-based knowledge on fatty liver in/of pregnancy. For NAFLD, a few large retrospective and prospective studies identify immediate and late risks for both the mother and the fetus. For AFLP, only small retrospective studies are available, indicating that prompt delivery and eventual referral to Liver Units for liver support or transplantation are mandatory to avoid maternal and fetal death. Expert opinion : The number of pregnant women with fatty liver is expected to increase in the next years. Pharmacologic treatment of NAFLD might be postponed, even when new drugs are approved by health authorities for the general population. In the case of AFLP, we need to improve our ability to correctly identify and treat the most severe cases not resolving with delivery.

Background and Aim: In patients with liver disease, etiology and body mass index (BMI) affects controlled attenuation parameter (CAP) assessment using FibroScan. We aimed to assess the performance characteristics of CAP for hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) stratified into obese (BMI ≥ 30 kg/m 2 ) and non-obese (BMI < 30 kg/m 2 ) subgroups., Methods: In this prospective study, 219 consecutive adult NAFLD patients, with an available FibroScan value (liver stiffness measurement-[LSM] and CAP) and liver biopsy, were included. Receiver operating characteristic curves were used for assessment of the CAP cut-off values predicting different stages of hepatic steatosis., Results: The mean ± standard deviation age of patients was 39.7 ± 10.5 years, 116 (53%) were males, and median (interquartile range) BMI was 31.8 (25.7-43.8) kg/m 2 . One hundred (45.7%) and 119 (54.3%) patients were non-obese and obese, respectively. The median values of CAP and LSM were significantly higher among obese patients as compared with the non-obese ones: 333 (304-368) vs. 320 (296-345) dB/m, p = 0.002 and 8.3 (6.1-11.4) vs. 6.6 (5.7-10.3) kPa, p = 0.012, respectively. Among non-obese NAFLD, optimal CAP cut-off values for steatosis (S) ≥ S1, ≥ S2, and ≥ S3 were 275 dB/m, 319 dB/m, and 337 dB/m, respectively. The corresponding CAP values among obese patients were higher as 285 dB/m, 340 dB/m, and 355 dB/m, respectively. BMI independently predicted CAP on multivariate analysis. The discordance of 2-grades between CAP and biopsy measured steatosis was seen in 13% in non-obese and 19.3% in obese NAFLD. CAP overestimated steatosis more often than underestimating it, with a higher proportion in obese NAFLD., Conclusion: In patients with NAFLD, interpretation of CAP requires consideration of BMI.

Background: Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear., Methods: We included participants from 2 cohorts of Danish children and adolescents: 1858 from a population-based cohort and 2155 with overweight or obesity, aged from 6 to 18 years. Age- and sex-specific percentile curves were calculated for fasting plasma concentrations of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and alkaline phosphatase (ALP) in both cohorts. Hepatic fat content was assessed by proton magnetic resonance spectroscopy in 458 participants., Results: Concentrations of ALT, AST, LDH, and ALP decreased with age in both girls and boys, while GGT and bilirubin were comparable across age groups in girls and increased slightly with age in boys. Children and adolescents with overweight or obesity exhibited higher concentrations of ALT in all age groups. Concentrations of ALT, and to a lesser degree GGT, increased with age in boys with overweight or obesity. Optimal ALT cut-points for diagnosing hepatic steatosis (liver fat content > 5%) was 24.5 U/L for girls (sensitivity: 55.6%, specificity: 84.0%), and 34.5 U/L for boys (sensitivity: 83.7%, specificity: 68.2%)., Conclusions: Pediatric normal values of liver enzymes vary with both age and sex. Overweight and obesity is associated with elevated biochemical markers of liver damage. These findings emphasize the need for prevention and treatment of overweight and obesity in children and adolescents. (J Clin Endocrinol Metab XX: 0-0, 2019)., (Published by Oxford University Press on behalf of the Endocrine Society 2019.)

Aims: To evaluate the significance of serum ceruloplasmin (CP) to diagnosis hepatic steatosis (HS) in Chronic hepatitis B (CHB) patients., Methods: A total of 360 CHB patients with HS (n = 136) or without HS (n = 224) were included. Relationships between CP and HS degrees were analyzed by Spearman rank correlation. HS-predictive models including CP were constructed using multivariate logistic regression analysis and compared to other HS predicting indexes., Results: Serum CP were significantly higher in CHB patients with HS than in patients without HS (P < 0.001) and were positively correlated with HS degree (r = 0.487, P < 0.001). The area under the receiver-operating characteristic curves (AUCs) of using CP to predict HS (S ≥ 1), moderate and severe steatosis (S ≥ 2) and severe steatosis (S = 3) were 0.758, 0.794 and 0.883, respectively. Multivariate analysis showed that CP, age, high density lipoprotein (HDL) and hemoglobin were independent predictors of HS, and CP, body mass index and HDL were independent predictors of moderate and severe HS. Two novel indexes for predicting HS of CHB patients were generated. The AUC of HSCHB-1 (for S ≥ 1) and HSCHB-2 (for S ≥ 2) were 0.881 and 0.916 in the training group, and 0.865 and 0.841 in the validation group, respectively. HSCHB-1 was superior to HS index (P < 0.001), fatty liver disease index (P = 0.0043) and steatosis index of patients with hepatitis B virus infection (P = 0.0029) in predicting HS in CHB patients., Conclusions: HS of CHB patients was positively associated with serum CP. HSCHB-1 and HSCHB-2 with inclusion of CP are two novel models for predicting HS in CHB patients., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)