Absence Of Steatosis Research Articles

Body mass index of 23 or greater is relevant to hepatic steatosis and fibrosis in patients with harmful alcohol use.

Steatotic liver disease, characterized by a combination of metabolic dysfunction, alcohol use, or specific etiologies, is a leading cause of chronic liver disease. However, the role of metabolic dysfunction in chronic liver disease with harmful alcohol use remains unclear. This study aimed to investigate factors associated with hepatic steatosis and fibrosis in patients with harmful alcohol use. Over a 2-year period, we registered patients with harmful alcohol use, defined by an Alcohol Use Disorders Identification Test score of 8 or higher. We retrospectively analyzed background information, blood test results, ultrasound-guided attenuation parameter (attenuation coefficient), and liver stiffness measurement. Hepatic steatosis was defined as attenuation coefficient ≥0.65dB/cm/MHz, and fibrosis as liver stiffness measurement ≥7.5kPa. The study included 131 patients (82% men, median age 59years). Linear regression analysis revealed significant associations with attenuation coefficient for body mass index ≥23 (0.08, p<0.0001) and age (-0.002, p=0.002). Liver stiffness measurement was associated with body mass index ≥23 (2.52, p=0.001), aspartate aminotransferase (0.02, p=0.0189), gamma-glutamyl transpeptidase (0.008, p<0.0001), platelet count (-0.02, p=0.001), and prothrombin international normalized ratio (26.40, p<0.0001). Among the four groups classified by the presence or absence of steatosis and fibrosis, patients with fibrosis, but without steatosis, demonstrated the lowest liver reserve. In contrast, patients with both steatosis and fibrosis showed higher aspartate aminotransferase and gamma-glutamyl transpeptidase levels. Body mass index is associated with both hepatic steatosis and fibrosis in patients with harmful alcohol use.

STEATOUS CHANGES IN HEPATOCYTES IN PATIENTS WITH CHRONIC HEPATITIS C

Background. The main consequences of progressing of a chronic hepatitis C are a cirrhosis of a liver and hepatocellular carcinoma. Considering that for last years number of cases of CHC disease among population of the world has essentially increased, creation of adequate methods of an estimation of morphological and metabolic shifts in a liver tissue at CHC is the important clinical problem.&#x0D; Aim: to determine the morphological features of steatosis in patients with CHC and assess its effect on the progression of hepatitis.&#x0D; Materials and methods. Under supervision there were 46 CHC patients in the age of 19 - 66 years, 36 men and 10 - women. Liver biopsy was carried out under the control of ultrasonic research with local anesthesia.&#x0D; Conclusion. Among CHC patients steatosis of a liver is observed in 60, 9% of supervised. Expressiveness of steatosis on Hornboll is distributed: 1-st degree at 13,0% of patients, 2-nd – 28,3%, 3-rd – 19,6%, absence of steatosis- at 39,1%. At initial stages of steatosis in hepatocytes of peripheral zone of segments the significant amount lysosomes, which look like lipofuscin granules which contain lipide, electronically-dense, small-sized granular, pigmentary component, safety of structure of organelles, hyperplasia mitochondrions. At expressed steatosis dense lipid vacuoles which borrow the most part of cytoplasm of hepatocytes, displace organelles, deform a kernel of cells, damage superficial membranes mitochondrions are observed. In periportal zone, on border of contact of hepatocytes which contain lipid granules, and lymphomonocytic infiltrate, the expressed activation of Kupfer cells, insufficiency of granules in cells of ITO, their transformation in fibroblasts, the expressed adjournment of collagenic fibers is observed.

Indian childhood cirrhosis: a retrospective study –redefining the older myths!

AimsThis retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management.MethodsThis study was done on liver archival...

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women

BackgroundLipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy.MethodsThis cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease.ResultsRegarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF.ConclusionsIn women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

Corrected and republished from: Metabolic associated liver disease.

Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.

Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages

Hepatic insulin resistance is recognized as a driver of type 2 diabetes and fatty liver disease but specific therapies are lacking. Here we explore the potential of human induced pluripotent stem cells (iPSCs) for modeling hepatic insulin resistance in vitro, with a focus on resolving the controversy about the impact of inflammation in the absence of steatosis. For this, we establish the complex insulin signaling cascade and the multiple inter-dependent functions constituting hepatic glucose metabolism in iPSC-derived hepatocytes (iPSC-Heps). Co-culture of these insulin-sensitive iPSC-Heps with isogenic iPSC-derived pro-inflammatory macrophages induces glucose output by preventing insulin from inhibiting gluconeogenesis and glycogenolysis and activating glycolysis. Screening identifies TNFα and IL1β as the mediators of insulin resistance in iPSC-Heps. Neutralizing these cytokines together restores insulin sensitivity in iPSC-Heps more effectively than individual inhibition, reflecting specific effects on insulin signaling and glucose metabolism mediated by NF-κB or JNK. These results show that inflammation is sufficient to induce hepatic insulin resistance and establish a human iPSC-based in vitro model to mechanistically dissect and therapeutically target this metabolic disease driver.

Gender and Liver Steatosis Discriminate Different Physiological Patterns in Obese Patients Undergoing Bariatric Surgery: Obesity Center Cohort.

Obesity is a major public health problem worldwide. Bariatric surgery can reduce body weight, and it is one of the better ways to improve metabolic disease and lifestyle. The aim of this study was to explore a new cohort of patients with obesity and evaluate the gender differences and the steatosis status within the gender group. A cohort of 250 adult obese patients with BMI ≥ 30 and age >18 years, eligible for gastric bariatric surgery at Pineta Grande Hospital, Castel Volturno (Italy) was studied. The prevalence in women was higher (72.40%) than men (27.60%). Overall, results indicated many statistically significant gender differences in hematological and clinical parameters. Analysis of the subcohorts based on the severity of steatosis revealed differences of this condition between the genders. Steatosis was more prevalent in the male subcohort, but female patients revealed greater within-group differences. Many differences were found not only in the total cohort but also between the gender subcohorts, both in the presence and absence of steatosis. We can conclude that the pathophysiological, genetic, and hormonal patterns affecting these patients delineate different individual profiles.

Prognostic Effects of Liver Fibrosis and Steatosis Determined Using Transient Elastography in Patients with Chronic Hepatitis B or C

The prognostic effects of liver fibrosis and steatosis in patients with chronic hepatitis B or C are unclear. We investigated the prognostic effects of liver fibrosis and steatosis determined through transient elastography (TE) in patients with chronic hepatitis B or C. This retrospective cohort study enrolled 5528 patients with chronic hepatitis B or C who received TE. Multivariate Cox regression was used to evaluate the associations between fibrosis and steatosis grades and the occurrence of hepatic-related events, cardiovascular events, and mortality. Liver stiffness measurements of ≥ 7.1, ≥ 9.5, and ≥ 12.5kPa were considered to indicate significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), and controlled attenuation parameters of ≥ 230 and ≥ 264dB/m were considered to indicate mild (S1) and moderate-to-severe (S2-S3) steatosis, respectively. During a median follow-up of 3.1years, 489 patients died, 814 had hepatic-related events, and 209 had cardiovascular events. The incidences of these outcomes were lowest among individuals with no- or mild-fibrosis (F0-F1), and increased with fibrosis severity. The incidence of adverse outcomes was highest among patients without steatosis (S0) and lowest among those with moderate-to-severe steatosis. Adjusted models indicated that F2, F3, and F4 were independent risk factors and that moderate-to-severe steatosis was a favorable marker for hepatic-related events. Cirrhosis was an independent factor for mortality. According to TE, increasing fibrosis grades and absence of steatosis were associated with higher risks of hepatic-related events, whereas cirrhosis was a risk factor for mortality in patients with chronic hepatitis B or C.

The Association between Coffee Consumption and Non-Alcoholic Fatty Liver Disease: Is there a Protective Role?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. Several studies have suggested a protective role of coffee in chronic liver disease, but their results remain controversial. AIM: The purpose of the study was to investigate the association between coffee consumption and the prevalence and severity of NAFLD in a non-diabetic and non-alcoholic population. METHODS: This study involved 157 participants. Cases were defined by the presence of steatosis on liver ultrasound, the severity of which was assessed by the Bright Liver Steatosis Score. Controls were defined by the absence of steatosis on liver ultrasound. All patients with cytolysis and/or cholestasis had an etiological investigation (serologic testing for Hepatitis B virus and hepatitis C virus infection, and autoimmune investigation). All participants underwent liver ultrasound, clinical assessment (blood pressure, waist circumference, and body mass index (BMI)), and biological assessment (Complete Blood Count, lipid profile test, liver function tests, and Fasting Blood Glucose [FBG]). Dietary assessment was conducted using a food frequency questionnaire, coffee consumption was dichotomized into present or absent and then categorized according to the number of cups consumed per day. RESULTS: The study included 94 NAFLD and 63 controls, the two groups were comparable in demographic characteristics. The means of systolic blood pressure, BMI, waist circumference, Aspartate Transaminase, Alanine Transaminase (ALT), Gamma-Glutamyl transferase (GGT), alkaline phosphatase, and FBG were significantly higher in the NAFLD group. The study of the association between coffee consumption and NAFLD showed a significant decrease in the risk of its occurrence (Odds Ratios [OR] = 0.39) and its severity (OR = 0.32) in coffee consumers, mainly in those consuming 3 or more cups. In multivariate analysis, the following factors were associated with increased prevalence of NAFLD: Metabolic syndrome, high mean levels of alkaline phosphatase, GGT, ALT, FBG, BMI, and waist circumference. However, Green tea consumption was not associated with either prevalence or severity of NAFLD (OR = 1.02, p = 0.82). CONCLUSION: Coffee consumption is inversely associated with the prevalence and severity of NAFLD. Further prospective studies are needed to establish a cause-effect relationship between coffee and NAFLD.

Triglyceride-Glucose Index and Hepatic Steatosis Index for the assessment of liver steatosis in HCV patients.

Liver steatosis in patients with chronic infection of hepatitis C virus (HCV) is important from multiple standpoints: faster disease progression, more frequent hepatocellular carcinoma and cirrhosis development or worse therapy response. Liver biopsy as diagnostic method, is in recent years more and more challenged due to its well-known flaws. Hepatic steatosis index (HSI) and triglyceride-glucose (TyG) Index, are surrogate scores developed in the first place for noninvasive assessment of steatosis in patients with nonalcoholic fatty liver disease (NAFLD). However, their use in the context of chronic hepatitis C (CHC) virus infection is still unclear. Aim of our study was to assess the accuracy of both HSI and TyG index in patients with CHC. The cohort included 814 patients with CHC infection in whom liver biopsy was performed. After implementing strict criteria for sample adequacy and necessary data, 424 patients were finally enrolled in our study. Histological findings were used as a reference point, and surrogate scores HSI and TyG index were expressed through receiver operating characteristic (ROC) curves in order to assess their ability in determining patients without (<5%) or with steatosis (>5%), but also to address their ability in assessing between different degrees of steatosis. The average age of study population was 37.09 years and the majority of patients were men (67%). Liver steatosis was detected in approximately half of the liver biopsy samples (50.4%). About 5% of them had severe steatosis. The area under the ROC curve values for HSI and TyG index when detecting liver steatosis were 0.76 and 0.629, respectively. Similar values were obtained comparing between absence of steatosis and mild steatosis (5-30%). Non-invasive surrogate scores HSI and TyG index in CHC patients, have good performance to detect the presence of steatosis. In this context, these tools are cheap, widely available and could be valuable asset in liver steatosis assessment outside liver biopsy.

Nonalcoholic non-virus-related hepatocellular carcinoma arising from nonsteatotic liver: Clinical and pathological features.

Nonalcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is considered to occur in steatotic livers; however, emerging evidence indicates that a subset of NANV-HCC occurs in nonsteatotic livers. Currently, little information is available regarding this subset. This study sought to provide the clinical and pathological features of NANV-HCC in nonsteatotic livers.We retrospectively investigated the clinicopathological features of 101 consecutive patients with NANV-HCC treated with a curative-intent hepatectomy. A background liver with <5% steatosis by area was regarded as a nonsteatotic liver. Survivals of patient subgroups were estimated using the Kaplan–Meier method, and log-rank tests were conducted to assess the survival difference. Multivariate analysis was performed with the Cox proportional hazards method.Overall, 34 of 101 patients with NANV-HCC were found to have a nonsteatotic liver. Vascular invasion of the tumor was more frequently observed in patients with a nonsteatotic liver than in those with a steatotic liver (P = .03). The extent of lobular inflammation and fibrosis did not differ between patients with and without steatosis in the liver. NANV-HCC with a nonsteatotic liver was independently associated with a shorter disease-free survival (DFS) (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.21–3.80; P = .009) and a shorter overall survival (OS) (HR 2.79; 95% CI 1.27–6.16; P = .01) than NANV-HCC with a steatotic liver.The absence of steatosis in the liver is independently associated with shorter DFS and OS in patients with NANV-HCC. Our findings indicate that nonsteatotic liver can be a surrogate phenotype of aggressive NANV-HCC.

Clinical relevance of lipid panel and aminotransferases in the context of hepatic steatosis and fibrosis as measured by transient elastography (FibroScan®).

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and is associated with various co-morbidities. Transient elastography (FibroScan®) is a non-invasive method to detect NAFLD using the controlled attenuation parameter (CAP). We aimed to evaluate the association of the lipid panel and aminotransferases concentrations with the presence or absence of steatosis and fibrosis.MethodsOne hundred and five patients with NAFLD were included. Hepatic steatosis was quantified by CAP (dB/m) and liver stiffness by Kilopascals (kPa), these values were then analyzed against patient lipid panel and serum concentrations of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A correlation and multiple regression were used. Mann-Whitney U test was used as non-parametric analysis.ResultsWe observed an association between hepatic steatosis and total cholesterol (B = 0.021, p = 0.038, Exp (B) = 1.021, I.C = 1.001-1.041) as well as serum triglycerides (B = 0.017, p = 0.006, Exp (B) = 1.018 and I.C = 1.005-1.030). Similarly, we found an association between significant hepatic fibrosis and lower concentrations of total cholesterol (B = -0.019, p = 0.005, Exp (B) = 0.982 I.C = 0.969-0.995) and elevated AST (B = 0.042, p = 3.25 × 10-4, Exp (B) = 1.043 I.C = 1.019-1.068) independent of age, gender and BMI.ConclusionsOur results suggest that, total cholesterol and triglyceride concentrations positively correlate with hepatic steatosis while significant hepatic fibrosis is associated with lower total cholesterol and higher AST concentrations.

The Capabilities of the Combi-Elasto and CEUS Ultrasound modes in the Diagnosis of Viral Hepatitis B

Purpose : To evaluate the capabilities of the Combi-Elasto and CEUS ultrasound modes in the diagnosis of viral hepatitis B on the clinical case example of the middle-aged patient with chronic viral hepatitis B in the acute stage. Material and methods : Comprehensive study of the patient's medical history, outpatient medical record, results of clinical, laboratory, instrumental and morphological methods with independent retrospective analysis of the histologic specimen of the liver. Results : The materials of observation and diagnostic search of the 54-year-old patient with chronic viral hepatitis B in the acute stage are presented. The diagnosis establishing took 3 months of examination in the infectious department and morphological study. This episode of the disease debuted with abdominal discomfort, weakness, yellowing of the sclera and skin, darkening of the urine and lightening of the feces. Survey the following results were obtained: Combi-Elasto data on admission — fibrosis F4 of the METAVIR scale (2.09), expressed process activity (1.60), absence of steatosis (0.54). At the initial stage, CEUS was performed with an assessment of quantitative and qualitative parameters on the same equipment, cirrhosis of the liver was excluded, chronic viral hepatitis, the acute stage was diagnosed, and appropriate treatment was prescribed. As a result of systematic observation after 3 months of repeated Combi-Elasto, the following results were obtained: fibrosis F1-2 of the METAVIR scale (1,30), average process activity (1.26), absence of steatosis (0.55). Conclusion : The presented clinical observation demonstrates the high efficiency of combining 2 modes (Combi-Elasto and CEUS) on the same equipment in the diagnosis of chronic viral hepatitis in the acute stage.

Liver MR relaxometry at 3T \u2013 segmental normal T1 and T2* values in patients without focal or diffuse liver disease and in patients with increased liver fat and elevated liver stiffness

Magnetic resonance (MR) T1 and T2* mapping allows quantification of liver relaxation times for non-invasive characterization of diffuse liver disease. We hypothesized that liver relaxation times are not only influenced by liver fibrosis, inflammation and fat, but also by air in liver segments adjacent to the lung – especially in MR imaging at 3T. A total of 161 study participants were recruited, while 6 patients had to be excluded due to claustrophobia or technically uninterpretable MR elastography. Resulting study population consisted of 12 healthy volunteers and 143 patients who prospectively underwent multiparametric MR imaging at 3T. Of those 143 patients, 79 had normal liver stiffness in MR elastography (shear modulus <2.8 kPa, indicating absence of fibrosis) and normal proton density fat fraction (PDFF < 10%, indicating absence of steatosis), defined as reference population. T1 relaxation times in these patients were significantly shorter in liver segments adjacent to the lung than in those not adjacent to the lung (p < 0.001, mean of differences 33 ms). In liver segments not adjacent to the lung, T1 allowed to differentiate significantly between the reference population and patients with steatosis and/or fibrosis (p ≤ 0.011), while there was no significant difference of T1 between the reference population and healthy volunteers. In conclusion, we propose to measure T1 relaxation times in liver segments not adjacent to the lung. Otherwise, we recommend taking into account slightly shorter T1 values in liver segments adjacent to the lung.

The Relationship Between the Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) with the Severity of Coronary Artery Disease (CAD) in Patients Undergoing Coronary Artery Angiography: A Cross- Sectional Study

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases worldwide. There are several common risk factors between NAFLD and coronary artery disease (CAD). Objectives: This study aims to evaluate the relationship between the prevalence of Non-alcoholic fatty liver disease (NAFLD) with severity of Coronary Artery Disease (CAD) in patients undergoing coronary artery angiography. Methods: This study was a cross-sectional, descriptive-analysis research that included 514 patients who underwent angiography. The severity of CAD was assessed by the number of vessels involved (vessel score: vd). An ultrasound was performed for all the patients also, intensity of fatty liver involvement was graded from zero (absence of steatosis) to three (severe steatosis). Results: Ultrasonographic examination proven NAFLD in 59.1% of patients with different grades. Patients with NAFLD had significantly higher body mass index (P < 0.001), waist circumference (P = 0.03), and age (P < 0.001). In addition, there were significant differences between ALT and AST within the normal group and NAFLD patients (P < 0.001). Moreover, coronary angiographic data indicated that the presence of NAFLD significantly correlated with the CAD severity score as so: 64% of people with 2vd and 60.5% of people with three-vessle lisense had fatty liver that was statistically significant (df = 4; P = 0.014). Conclusions: This study showed a high prevalence of NAFLD in patients with documented CAD. It is extremely important since knowing risk factors, designing screening programs, and early treatment of fatty liver could lead to reducing the risk of cardiovascular diseases.

The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients.

Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR=2.09, 95% CI=1.12-3.9, P=.021), the presence of DM without steatosis (HR=2.78, 95% CI=1.3-5.92, P=.008) and the combined presence of steatosis and DM (HR=3.25, 95% CI=1.44-7.33, P=.004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.

Increased liver AGEs induce hepatic injury mediated through an OST48 pathway

The protein oligosaccharyltransferase-48 (OST48) is integral to protein N-glycosylation in the endoplasmic reticulum (ER) but is also postulated to act as a membrane localised clearance receptor for advanced glycation end-products (AGE). Hepatic ER stress and AGE accumulation are each implicated in liver injury. Hence the objective of this study was to increase the expression of OST48 and examine the effects on hepatic function and structure. Groups of 8 week old male mice (n = 10–12/group) over-expressing the gene for OST48, dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST+/−), were followed for 24 weeks, while randomised to diets either low or high in AGE content. By week 24 of the study, either increasing OST48 expression or consumption of high AGE diet impaired liver function and modestly increased hepatic fibrosis, but their combination significantly exacerbated liver injury in the absence of steatosis. DDOST+/− mice had increased both portal delivery and accumulation of hepatic AGEs leading to central adiposity, insulin secretory defects, shifted fuel usage to fatty and ketoacids, as well as hepatic glycogen accumulation causing hepatomegaly along with hepatic ER and oxidative stress. This study revealed a novel role of the OST48 and AGE axis in hepatic injury through ER stress, changes in fuel utilisation and glucose intolerance.

Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma.

Preoperative serum inflammatory markers have been correlated with outcome after resection of hepatocellular carcinoma (HCC), but studies have had conflicting results. This study aimed to evaluate the association of six inflammatory markers with recurrence-free survival (RFS), overall survival (OS), and microvascular invasion (MVI), a well-known prognostic factor. This study investigated 370 patients who underwent resection of HCC from 1992 to 2016, retrospectively evaluating their inflammatory indices and individual components including their neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase-to-neutrophil ratio index (ANRI). Uni- and multivariate analyses were performed to evaluate these markers for RFS, OS, and MVI. The median RFS was 23months, and the median OS was 60months. Factors independently associated with worse RFS were higher PLR and alpha-fetoprotein level, male gender, and the presence of MVI as well as multiple nodules. Factors independently associated with worse OS were higher PLR and international normalized ratio, male gender, older age, presence of MVI and multiple nodules, larger tumor, presence of cirrhosis, and absence of steatosis. The study identified MVI in 47% of the patients. Lower level of albumin, higher level of alpha-fetoprotein, and larger tumor on preoperative imaging were independently associated with MVI. This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

The impact of cortisol in steatotic and non-steatotic liver surgery.

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia–reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol–acetylcholine–M3 muscarinic receptors.

Sonography Predicts Liver Steatosis in Patients With Chronic Hepatitis B.

Liver inflammation and fibrosis may impair the ability of sonography to identify steatosis. We determined the accuracy of sonography in grading steatosis in patients with chronic hepatitis B compared to liver biopsy. We conducted was a single-center retrospective study of all nontransplanted patients with chronic hepatitis B undergoing sonography and liver biopsy between 2004 and 2014 (n = 109). Steatosis was graded by sonography as none, mild, moderate, or severe. Liver histologic analysis graded steatosis (0, <5%; 1, <33%; 2, <66%; or 3, ≥66%) and staged fibrosis (F0-F4). Severe steatosis was defined as grade 2 or 3. Clinical variables within 6 months of liver biopsy were collected, and the association with steatosis was analyzed by univariate logistic regression. Patients were predominantly Asian (83%), male (62%), and hepatitis B e antigen negative (62%). Twenty-nine percent of patients were obese; 9% had diabetes mellitus; 23% had hypertension; and 31% had dyslipidemia. Forty-four percent of patients had steatosis on liver biopsy; 8% had severe steatosis. The presence of any steatosis on sonography correctly identified any steatosis on liver biopsy in 29 of 48 patients (60%). The absence of steatosis on sonography ruled out severe steatosis on biopsy (specificity, 100%). Severe steatosis on sonography correctly predicted the presence of severe steatosis on liver biopsy (89%; P < .001); however, it was not accurate at distinguishing between steatosis grades. Predictors of biopsy-proven steatosis on univariate analysis included diabetes (P < .001), hypertension (P = .03), hypercholesterolemia (P = .02), and body mass index (P < .001). Sonography had excellent accuracy in identifying patients with steatosis on biopsy. Abdominal sonography can be used to predict clinically important steatosis in patients with chronic hepatitis B.