Grades Of Non-alcoholic Fatty Liver Disease Research Articles

Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease.

Psoriasis is a chronic, immune-mediated inflammatory skin disease with many extracutaneous manifestations. Several recent studies have indicated an increased prevalence of nonalcoholic fatty liver disease (NAFLD) among patients with psoriasis. In the present study, we investigated the prevalence of NAFLD in a population of Iranian patients with psoriasis. NAFLD was assessed and graded using ultrasonography in 123 patients with psoriasis and 123 healthy controls (HCs) matched by age, sex and body mass index (BMI). The prevalence of NAFLD was significantly higher in the psoriatic group compared with the HC group (65.6% vs. 35%, P<0.01, OR=3.53). Median NAFLD grade was significantly greater in patients with psoriasis compared with HCs (grade 2 vs. grade 1, P<0.01). In patients with psoriasis, NAFLD was associated with a higher frequency of hypertension (16.5%), abnormal liver function test (LFT) results (16.4%) and metabolic syndrome (46.6%). Moreover, patients with psoriasis and NAFLD tended to have significantly higher values for BMI, waist circumference (WC), Psoriasis Activity and Severity Index (PASI), and levels of serum triglyceride, cholesterol, low-density lipoprotein and fasting blood sugar (FBS). Multivariate logistic regression revealed that WC, PASI, LFT abnormalities, hypertension and cigarette smoking were independent predictors of NAFLD grade. Our findings warrant a detailed assessment of metabolic comorbidities including NAFLD in patients with a primary diagnosis of psoriasis. Lifestyle modifications, including weight loss and smoking cessation, may be necessary for patients with psoriasis to decrease the risk and severity of NAFLD.

Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients.

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index>40kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23±9.80years), HOMA-IR (6.74±1.62), total cholesterol (219.7±9.58mg/dl), aspartate aminotransferase (36.25±3.24UI/l), gamma-glutamyl transpeptidase (37.12±3.41UI/l), and TNF-α (37.41±1.72pg/ml) as well as decreased serum levels of IL-10 (61.05±2.43pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

Self-reported eating speed in relation to non-alcoholic fatty liver disease in adults

Non-alcoholic fatty liver disease (NAFLD), known to be related to insulin resistance, has been the focus of intensive research efforts due to its increasing prevalence and clinical significance. Rapid eating behavior is another emerging health issue associated with insulin resistance. We aimed to clarify the correlation between self-reported eating speed and NAFLD, both known to be related to insulin resistance. A cross-sectional study was conducted during routine medical checkups on 7,917 consecutively enrolled participants. Anthropometric, biochemical, nutritional, and social parameters were checked. The self-reported eating speed per their usual meal (<5, 5-10, 10-15, and more than 15 min) was recorded by a registered dietitian. The faster eating groups had a higher proportion of NAFLD, and the grade of NAFLD was advanced. After controlling for anthropometric, cardiometabolic, social, and nutritional parameters, the fastest eating group (<5 min) showed an increased risk of NAFLD compared with the lowest eating speed group (≥15 min) both in total [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.24-2.63] and the participants with BMI < 25 kg/m(2) (OR 1.79, 95% CI 1.22-2.61). As the self-reported eating speed increased, the risk of NAFLD also increased in total and those with BMI < 25 kg/m(2) (P for trend <0.001). Fast eating is associated with an increased risk of the presence and grade of NAFLD in Korean adults, especially those with BMI < 25 kg/m(2), since presence of overweight or obesity may be overwhelming the effect on NAFLD.

The Effects of Dark Chocolate Consumption on Lipid Profile, Fasting Blood Sugar, Liver Enzymes, Inflammation, and Antioxidant Status in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Pilot study

Background : Nonalcoholic fatty liver disease (NAFLD) is an important health problem in the world and despite the rising prevalence, there is currently no satisfying therapeutic strategy for curing NAFLD. Dark chocolate (DC) is a food rich in phenolic antioxidants, which may exert favorable and modifying effects on lipid profile, insulin resistance, oxidative stress, and metabolic effects. This study aims to investigate the possible effects of DC consumption on the lipid profile, fasting blood sugar (FBS), liver transaminases (ALT, and AST), inflammatory, and antioxidant status in NAFLD patients. Materials and Methods: In this double-blind, placebo-controlled trial, 42 patients with NAFLD were randomly allocated to 2 groups: the treatment group (n=21) whom received 30 gr dark chocolate (83%) daily and the control group (n=21), for a 12 weeks period. Results: During the intervention, taking 30 gr DC (83%) daily resulted in a significant decrease in AST (P=0.012), body weight (P=0.027), and BMI (P=0.042) in the treatment group. In addition, patients who received DC had considerable changes in serum HDL ( P = 0.044). However, no significant changes occurred in serum levels of ALT, hs-CRP, anthropometric measures (WC, HC, and WHR), and grades of NAFLD in both groups (P>0.05). Conclusion: DC consumption can decrease the level of AST in patients with NAFLD and could be a potential therapeutic approach. We recommend more investigation about potential therapeutic effects of dark chocolate to be further clarified.

Relationship between serum circulating insulin‐like growth factor‐1 and liver fat in the United States

Nonalcoholic fatty liver disease (NAFLD), circulating insulin-like growth factor-1 (IGF-1), and IGF-1/IGF-binding protein-3 (IGFBP-3) concentrations are associated with adiposity and insulin resistance. We aimed to determine whether serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with presence or severity of NAFLD independent of potential confounding. We performed a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988–1994, a representative sample of the United States adult population. Among participants who had a fasting blood draw and ultrasound examination, we excluded those with missing data, viral hepatitis, iron overload, excessive alcohol intake, pregnancy, or taking glucose-lowering therapy, yielding 4172 adults for this analysis. In logistic regression analyses adjusted for age, gender, and race/ethnicity, higher IGF-1 and IGF-1/IGFBP-3 quartiles were associated with lower likelihood of NAFLD and lower grade steatosis. These associations became non-significant when further adjusted for adiposity (body mass index, waist circumference) with the exception of the association between IGF-1/IGFBP-3 and severity of NAFLD which remained significant after adjustment for homeostasis model assessment for insulin resistance (HOMA-IR) (odds ratio [95% CI]: Q3: 0.71 [0.53–0.96], Q4: 0.62 [0.43–0.89]) and adiposity (Q4: 0.67 [0.47–0.96]). Full adjustment (age, gender, race/ethnicity, adiposity, HOMA-IR, A1C%) further attenuated associations between IGF-1 or IGF-1/IGFBP-3 and liver fat such that they were no longer significant. Adiposity explains much of the observed association between IGF-1 or IGF-1/IGFBP-3 and liver fat. These findings do not support a direct role for the growth hormone-IGF-1/IGFBP-3 axis in the pathophysiology of NAFLD.

Effect of non-alcoholic fatty liver disease on carotid artery intima-media thickness as a risk factor for atherosclerosis.

This study aimed to evaluate the effect of NAFLD on CIMT as a risk factor for atherosclerosis. The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide due to rise of obesity and diabetes mellitus (DM) prevalence. Non-invasive assessment of carotid intima-media thickness (CIMT) by high-resolution carotid B-mode ultrasonography is widely used for determining the atherosclerosis. In this case-control setting, 151 subjects were categorized in three groups: group I including 49 patients with NAFLD and DM; group II including 50 non-diabetic NAFLD patients; and the control including 52 normal subjects as group III. The right and left CIMTs and its maximum reading (CIMTmax) were measured by a skilled sonographist blind to the groups. The sonographic grading of the NAFLD was determined in group I and II. Median CIMTmax was significantly higher in group I comparing with group II and control group (p<0.001). This difference between group I and group II was not significant after adjusting for age and history of hypertension and hyperlipidemia (p=0.089). After controlling the confounders, there was statistical significant between group I and group II with the control group (p<0.05). There was no significant difference in median maximal thickness of intima-media in the carotid of group I compare to group II in patients with and without elevated liver enzymes (in both groups, 0.6 mm, p= 0.402). Based on our findings, there is a significant association between the presence of NAFLD and atherosclerosis. This association was independent to the DM presence. The grade of NAFLD and elevated liver function tests had no effect on severity of atherosclerosis.

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease.

Background:Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S).Objectives:This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography.Materials and Methods:During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis.Results:Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors.Discussion:Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a predictor can be helpful. But, AST has not been a reliable finding, because it changes in many conditions.

Comparison of lipid profile in different grades of non-alcoholic fatty liver disease diagnosed on ultrasound

ObjectiveTo detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatty liver on ultrasonography. MethodsA total of 70 cases which included 30 males and 40 females, diagnosed as non-alcoholic fatty liver disease (NAFLD) on ultrasound were investigated with serum lipid profile. Then a comparison of lipid abnormalities between different grades of fatty liver diagnosed on ultrasound was done. P value was calculated by using analysis of variance test (ANOVA) and P value <0.05 was considered as statistically significant. ResultsOut of 70 cases which were diagnosed as NAFLD on ultrasonography, grade I NAFLD cases were 47.15%, grade II were 42.85% and grade III were 10%. The mean age of the patients was 49.14 years. Male to female ratio was 3:4. Serum triglycerides, total cholesterol, LDL and VLDL levels were raised in 67.14%, 45.71% 34.28%, 25.71% of cases respectively. Low serum HDL levels were seen in 62.85% of patients. On statistical analysis we found increasing grades of NAFLD were significantly associated with increasing values of total cholesterol (P value-0.001), LDL (P value-0.000) and VLDL (P value-0.003) and decreasing HDL (P value-0.000). ConclusionMost of the patients of NAFLD in India is asymptomatic, non-diabetic and non-hypertensive. Though liver biopsy is the gold standard method for diagnosis of NAFLD, Ultrasonography which is non-invasive, simple tool, can be used for the early detection of NAFLD in asymptomatic patients.

MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis as the earliest manifestation and hallmark, and ranges from benign fatty liver to non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is considered the reference standard for NAFLD diagnosis, grading and characterization, but it is limited by its invasiveness and observer-dependence. Among imaging surrogates for the assessment of hepatic steatosis, MR is the most accurate. (1)H MR spectroscopy (MRS) provides a quantitative biomarker of liver fat content (LFC) called proton density fat fraction (PDFF), but it is time-consuming, not widely available and limited in sample size. Several MR imaging (MRI) techniques, in particular fat suppression and in-opposed phase techniques, have been used to quantify hepatic steatosis, mainly estimating LFC from water and fat signal intensities rather than proton densities. Several technical measures have been introduced to minimize the effect of confounding factors, in particular a low flip angle, a multiecho acquisition and a spectral modeling of fat with multipeak reconstruction to address respectively T1 effect, T2* effect, and the multifrequency interference effects of fat protons, allowing to use MRI to estimate LFC based on PDFF. Tang et al. evaluated MRI-estimated PDFF, obtained by applying the above-mentioned technical improvements, in the assessment of hepatic steatosis, using histopathology as the reference standard. The identification of PDFF thresholds, even though to be further explored and validated in larger and more diverse cohorts, is useful to identify steatosis categories based on MRI-based steatosis percentages. MRI, with the new refined techniques which provide a robust quantitative biomarker of hepatic steatosis (PDFF) evaluated on the whole liver parenchyma, is a promising non-invasive alternative to LB as the gold standard for steatosis diagnosis and quantification.

Nonalcoholic Fatty Liver Disease and Severity of Cardiovascular Disease Manifestations

Nonalcoholic fatty liver disease (NAFLD), characterized by the accumulation of fat in the liver cells in the absence of excessive alcohol intake and other liver disease, affects approximately 15% to 30% of the general population in various countries; its prevalence increases up to 70% to 90% in people with obesity, metabolic syndrome (MetS), or type 2 diabetes mellitus (T2DM). The histological manifestations of NAFLD range from simple steatosis, steatohepatitis (nonalcoholic steatohepatitis [NASH]), liver fibrosis, cirrhosis, and, rarely, hepatocellular carcinoma. The NAFLD is considered to be the hepatic manifestation of the MetS. The NAFLD is strongly associated with increased risk of cardiovascular disease (CVD), and NAFLD is not only a marker but also an early mediator of atherosclerosis. The risk of clinical manifestations of CVD is significantly higher in individuals with NASH than in those with simple steatosis, and the histological severity of NAFLD (ie, steatosis, necroinflammation, and fibrosis) predicts CVD independent of classical risk factors, insulin resistance, and components of the MetS. This suggests that NAFLD might itself confer a degree of CVD risk above and beyond that associated with the individual components of MetS. Key issues remaining to be investigated are the association of NAFLD presence and/or grade (stage) with the severity, and therefore, the prognosis of CVD manifestations (coronary artery disease [CAD], stroke, and peripheral arterial disease [PAD]) and our ability to tackle the negative effect of NAFLD on CVD morbidity and mortality. The results of the study by Agac et al, published in this issue of Angiology, suggest that the prevalence of NAFLD was very high (81.2%) among subjects with acute coronary syndromes (ACS) and that the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) may represent a prognostic marker in patients with both non-ST and ST segment elevation ACS. The SS is an angiographic variable that predicts 1-year mortality rates, cardiac death, myocardial infarction, and target vessel revascularization in patients undergoing percutaneous coronary intervention (PCI) and its value is significantly higher in patients with NAFLD than in those without NAFLD (18 + 8 vs 11+ 5, P 1⁄4 .001). Furthermore, in multivariate analysis, increased age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.00-1.10) and the presence of NAFLD (OR, 13.20; 95% CI, 2.52-69.15) were independent factors associated with the SS value. This suggests that the presence of NAFLD was associated with a more severe CAD, which is bound to have a worse prognosis. Among the limitations of this study are the cross-sectional design and therefore its inability to confirm findings on the rate of CVD events. Moreover, the use of the SS has been mainly validated in the Acute Catheterization and Urgent Intervention Triage StrategY trial only in patients with a non-ST-segment elevation ACS undergoing PCI, and its use in patients with ST elevation ACS might be challenged. Initially, the SS was shown to be an effective tool for predicting the risk of major ischemic events in patients with stable CAD and multivessel or left main disease undergoing PCI, and there are data suggesting a moderate intraobserver reproducibility (its calculation relies on the subjective assessment of lesions using coronary angiography). Nevertheless, the findings of this study are adequate to act as hypothesis generating and should encourage the design of bigger and long-term studies that will prospectively investigate the relationship between the presence and the histological stage of NAFLD with actual midor long-term prognosis of CVD. Moreover, these results might motivate the initiation of interventions to control and, if possible, to reverse the progress of NAFLD from steatosis to a more advanced stage, given that at present time, there is no globally accepted effective intervention for NAFLD. There are some data suggesting a close relationship of NAFLD with the severity of CAD. To begin with, there are very few data on NAFLD and ACS. The most common cause of ACS appears to be vulnerable plaque rupture. These are related to a positive remodeling of the vessel, a large lipid

Predictive Factors for Ultrasonographic Grading of Non-Alcoholic Fatty Liver Disease

BackgroundThere are several studies in the literature investigating factors which can induce non-alcoholic fatty liver disease (NAFLD) in different populations. However, the existing literature lacks powerful studies addressing the factors which may predict the severity of NAFLD.ObjectivesIn the current study, we aimed to evaluate factors independently associated with liver echogenicity in an Iranian NAFLD patient population.Patients and MethodsA total of 393 patients attending as outpatients at the Hepatology Clinic of Baqiyatallah University of Medical Sciences were entered into this analysis. Univariate and multivariable linear regression models were performed to evaluate the effects of the study variables on the NAFLD grade, defined by ultrasound hepatic echogenicity.ResultsUnivariate linear analyses revealed a significant relationship between; the ultrasonographic grading of NAFLD and body weight (P < 0.001), abdominal girth (P = 0.007), pelvic girth (P = 0.032), fasting blood glucose (FBS) (P = 0.005), serum insulin (P = 0.035), hemoglobin A1c (HbA1c) (P = 0.012), triglycerides (P = 0.049), aspartate aminotransferase (AST) (P = 0.015), alanin aminotransferase (ALT) (P = 0.026), and homeostasis model assessment (HOMA) (P = 0.002). Multivariable linear regression models left only; HbA1C (P = 0.011, β = 0.133), body weight (P = 0.001; β = 0.176) and serum triglyceride (P = 0.034; β = 0.112) as factors independently associated with liver echogenicity.ConclusionsDiabetic patients can reduce liver damage of NAFLD with control of their HbA1C through the lower ranges. Hypertriglyceridemia and body weight are the other implicated factors, which worsen hepatic echogenicity in the NAFLD patient population. We recommend future prospective studies and clinical trials to confirm our findings.

Association Between Nonalcoholic Fatty Liver Disease and Cardiovascular Risk in Obese Children and Adolescents

BackgroundThe recent rise in the prevalence of obesity likely explains nonalcoholic fatty liver disease (NAFLD) epidemic worldwide. We evaluated cardiac functions, cardiovascular risk, and associated parameters with grades of NAFLD in obese children. MethodsFour hundred obese children were enrolled in the study. Obese children with NAFLD were classified in 2 subgroups according to ultrasonographic visualizing. Ninety-three obese children with NAFLD (mean age 11.73 ± 2.72 years in group 2 and 12.69 ± 2.61 years in group 3) were compared with 307 age- and sex-matched non-NAFLD obese children and 150 control subjects. Laboratory parameters were measured during the fasting state. Pulsed and tissue Doppler echocardiography were performed. Intima-media (IMT) and epicardial adipose tissue (EAT) thicknesses were measured. ResultsNAFLD groups had a significantly higher body mass index (29.15 ± 3.42 and 30.46 ± 4.60; P < 0.001), total adipose tissue mass (37.95 ± 4.46% and 46.57 ± 6.45%; P < 0.001), higher insulin, alanine aminotransferase, and aspartate aminotransferase levels. Increased end-systolic thickness of the interventricular septum (P < 0.001), larger left ventricular mass (P < 0.003) and index (P < 0.003) were found in NAFLD groups. Children with NAFLD had higher Tei index values. Also, carotid artery IMT and EAT thickness were significantly higher in obese children. Waist and hip circumference, total cholesterol level, total adipose tissue mass, and interventricular septum were statistically different in NAFLD groups. ConclusionsChildren with NAFLD had mildly altered left and right ventricular functions and all obese children had increased IMT and EAT thickness. Also, grade of liver steatosis was positively correlated with total adipose tissue mass and interventricular septum systolic thickness.

Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease

Pediatric non-alcoholic fatty liver disease (NAFLD) may present with a distinct histopathological pattern characterized by the presence of predominant portal-based injury and portal inflammation (PI). We aimed at developing a new grading score for pediatric NAFLD to be used in clinical trials that takes into account the presence of PI and the weight of histological features. Our training set consisted of 203 children with biopsy-proven NAFLD. The diagnosis of non-alcoholic steatohepatitis (NASH) was based on Brunt's criteria. Histological features were scored: steatosis (0-3), lobular inflammation (0-3), ballooning (0-2), and PI (0-2). Logistic regression analysis was performed to apply weight to each feature. The new score was called the Pediatric NAFLD Histological Score or PNHS. The validation set consisted of 100 children with NAFLD. The mean age of the initial cohort was 12.4 ± 3.4 years and significant fibrosis (fibrosis stage ≥ 2) was present in 26 patients (12.8%). NASH was diagnosed in 135 patients with a mean NAS of 4.5 ± 1.4. The mean PNHS in the NASH group was 89 ± 20.5 compared to 21.9 ± 24.5 in the "not NASH" group, p<0.001. PNHS correlated with the presence of NASH according to the pathologist's diagnosis, better than the NAFLD activity score (NAS), p=0.011. The area under the ROC curve (AUC) for the diagnosis of NASH was 0.96 for PNHS. Similar findings were observed in the validation set with an AUC of 0.94. PNHS may be used for histological grading of pediatric NAFLD with excellent correlation with the presence of NASH.

Clinical Predictors of Different Grades of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the comorbidities related to obesity. Liver biopsy has been used as the "gold standard" for the diagnosis, grading, and prognosis of obese patients. The objective of the present study was to evaluate clinical predictors of more advanced stages of NAFLD. In this retrospective study we assessed several physical and laboratorial factors, including some cytokines, in morbidly obese patients submitted to Roux-en-Y gastric bypass that could be related to the diagnosis and staging of NAFLD. Fragments of the livers were obtained from wedge biopsies during operation. The medical records of 259 patients were studied. The patients were divided into four groups: normal hepatic biopsy, steatosis, mild nonalcoholic steatohepatitis (NASH), and moderate and severe NASH. There were no differences in cytokine levels among groups. The triglyceride levels were the only variable that could stratify the grades of NAFLD and also differentiate from normal livers in the female patients. Also in this group, the aminotransferases and GGT levels and fasting glucose were predictors of the more advanced stages of NASH, while BMI and weight were predictors of the more advanced stages of NASH in male patients. There are no available markers in clinical practice to detect the initial stages of NAFLD. It is very important to perform a liver biopsy in all patients submitted to bariatric surgery and in obese patients with no indication to be operated in the presence of elevated blood levels of aminotransferases, GGT, and fasting glucose.

Hepatocellular ballooning in nonalcoholic steatohepatitis: the pathologist’s perspective

Nonalcoholic fatty liver disease (NAFLD) is an important complication of the metabolic syndrome. The increasing prevalence of the metabolic syndrome is paralleled by an increasing prevalence of NAFLD, which has become one of the most common chronic liver diseases. NAFLD comprises a morphological spectrum ranging from nonalcoholic fatty liver (NAFL), characterized by accumulation of fat in hepatocytes, to nonalcoholic steatohepatitis (NASH). The key histological features of NASH accepted by most pathologists include steatosis, hepatocellular ballooning and lobular inflammation, whereas, like in other chronic liver diseases, the presence of fibrosis is not considered a requirement for the diagnosis. The diagnosis of NASH and the distinction from NAFL carries important prognostic and therapeutic implications because NASH, in contrast to NAFL, is associated with an increased risk of progression to cirrhosis and hepatocellular carcinoma. Hepatocellular ballooning is a key feature required for the diagnosis of NASH and a component of currently used histological grading and staging systems of NAFLD. However, it represents an ill-defined form of liver cell injury associated with cell swelling and rounding of the cytoplasm, the detection of which is prone to intra- as well as inter-observer variation. Some of the factors that may contribute to ballooning are the rearrangement of the intermediate filament cytoskeleton, accumulation of small-droplet fat in the cytoplasm and dilation of the endoplasmic reticulum. The rearrangement of the intermediate filament cytoskeleton can be demonstrated by the loss of keratin 8/18 immunostaining of the cytoplasm, and may thus be evaluated in the future as a marker for the more objective detection of hepatocellular ballooning in NASH.

Influencia de la quimioterapia preoperatoria en el parénquima hepático y en la evolución posquirúrgica de pacientes sometidos a hepatectomía por metástasis de carcinoma colorrectal

Introduction The aim of the study was to evaluate the relationship between the pre-surgical administration of a chemotherapy regime based on irinotecan or oxaliplatin and the development of non-alcoholic fatty liver disease (NAFLD) or sinusoidal obstruction syndrome (SOS), and the influence of these histological changes on the outcome of patients after surgical intervention. Patients and method A prospective study which included 45 patients surgically intervened due to colorectal cancer liver metastases between May 2005 and July 2009. Demographic data and the variables before during and after the operation were collected. A specimen of the resection was obtained for histological analysis following the classification parameters of the NAFLD (NASH index) and SOS scale. Results Neoadjuvant chemotherapy was given before the resection in 22 cases (study group) and 23 patients made up the control group (no chemotherapy). Borderline or diagnostic steatohepatitis was observed in 4 of the 7 patients (57.2%) who were given preoperative irinotecan ( P=0.001). Seven of the 15 patients (46.7%) treated with oxaliplatin developed a moderate or severe SOS ( P=0.002). There were no differences in morbidity or mortality associated to the NAFLD grade, but there was a higher rate of liver complications and longer mean hospital stay in patients with moderate/severe SOS ( P=0.004 and P=0.021, respectively). Conclusions Treatment with irinotecan was significantly associated with an increase in the incidence of steatohepatitis, but did not increase the morbidity or mortality. Patients treated with oxaliplatin had a higher incidence of SOS, an increase in liver complications and a longer mean hospital stay.

Non-alcoholic fatty liver disease in subjects with type 2 diabetes mellitus and non-diabetics with special reference to insulin resistance and hepatic histopathological changes

Aims Non alcoholic fatty liver disease (NAFLD) includes simple steatosis and non alcoholic steatohepatitis (NASH). The present study was intended to evaluate insulin resistance (IR) in patients with NAFLD and correlate Insulin resistance [IR] with histopathological grades of liver involvement. Material and Methods It constituted of forty two consecutive patients (ultrasonographically established) with fatty liver admitted to our hospital. Ninteen were patients with Type 2 diabetes mellitus, 23 were normoglycemic and 12 age-matched healthy persons served as controls. IR was assessed by using HOMA-IR. Histopathological grading and staging of NAFLD was done as per Brunt system. Results Diabetics had significantly higher IR than both the other groups while non diabetics with NAFLD also had higher IR (p < 001) than controls. There was no difference in the HDLc values between the three groups, whereas all other lipid parameters were higher in the patients. The IR was significantly higher 6.83(±2.51) in patients with grade 3 NASH as compared to patients with grade I changes 3.04(±1.58) (p < 0.05) irrespective of glycemic status. Similarly, the level of total cholesterol was significantly higher in patients with grade-3 NASH as compared to grade-1. Serum billirubin and liver enzymes (AST, ALT, ALP) were significantly higher in subjects with Grade 3 NASH when compared with Grade-1. Conclusion Insulin resistance and dyslipidemia rather than the glycemic status.were the determinant factors that had positive correlation with higher histopathological grades of NAFLD.

The role of adiponectin in the pathogenesis and treatment of non‐alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD. Adiponectin is the most abundant and adipose-specific adipokine. In the liver, adiponectin acts through the activation of 5-AMP-activated protein kinase and peroxisome proliferator-activated receptor-alpha pathways and inhibition of toll-like receptor-4 mediated signalling. There is an evidence that adiponectin decreases hepatic and systematic IR and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and severity of NAFLD, but it remains to be addressed to what extent this is a direct effect or related to the presence of more severe IR. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. Weight loss, through diet, lifestyle changes and/or medications including orlistat, sibutramine, rimonabant or bariatric surgery, increase adiponectin and may improve liver histology. Insulin sensitizers, including pioglitazone and rosiglitazone, and lipid-lowering agents, including statins and fibrates, also upregulate adiponectin and ameliorate liver histology. The wider use of new treatment approaches appears to signal the dawn of a new era in the management of NAFLD. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are systematically analysed.

Influence of pre-surgical chemotherapy on liver parenchyma and post-surgical outcome of patients subjected to hepatectomy due to colorectal carcinoma metastases

IntroductionThe aim of the study was to evaluate the relationship between the pre-surgical administration of a chemotherapy regime based on irinotecan or oxaliplatin and the development of non-alcoholic fatty liver disease (NAFLD) or sinusoidal obstruction syndrome (SOS), and the influence of these histological changes on the outcome of patients after surgical intervention. Patients and methodA prospective study which included 45 patients surgically intervened due to colorectal cancer liver metastases between May 2005 and July 2009. Demographic data and the variables before during and after the operation were collected. A specimen of the resection was obtained for histological analysis following the classification parameters of the NAFLD (NASH index) and SOS scale. ResultsNeoadjuvant chemotherapy was given before the resection in 22 cases (study group) and 23 patients made up the control group (no chemotherapy). Borderline or diagnostic steatohepatitis was observed in 4 of the 7 patients (57.2%) who were given preoperative irinotecan (p=.001). Seven of the 15 patients (46.7%) treated with oxaliplatin developed a moderate or severe SOS (p=.002). There were no differences in morbidity or mortality associated to the NAFLD grade, but there was a higher rate of liver complications and longer mean hospital stay in patients with moderate/severe SOS (p=.004 y p=.021, respectively). ConclusionsTreatment with irinotecan was significantly associated with an increase in the incidence of steatohepatitis, but did not increase the morbidity or mortality. Patients treated with oxaliplatin had a higher incidence of SOS, an increase in liver complications and a longer mean hospital stay.

Serum α-fetoprotein levels in liver steatosis

Nonalcoholic fatty liver disease (NAFLD) is a common disorder and becoming a leading cause of cirrhosis in the western world. The monitoring of the disease is challenging and the prognostic importance of α-fetoprotein (AFP) level elevation in NAFLD remains uncertain. Eighty-four patients were evaluated in the study. Patients with evidence of fatty liver in an abdominal ultrasonography performed for any reason were enrolled in the study. Degree of liver steatosis was graded into three groups. As a control group, patients without fatty liver or other liver diseases were included. All patients and controls were asked about prior hepatic diseases, consumption of alcohol, smoking, drug use, and a physical examination, biochemical analyses including liver function tests, different components of the metabolic syndrome, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) score were also performed. Body mass index, aspartate aminotransferase, alanine aminotransferase, glucose, insulin, and HOMA-IR in patients with NAFLD were higher than in control group. Triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol levels were higher in NAFLD group than in control group. A statistically significant increase in AFP levels was noted in patients with NAFLD (4.09±1.68) when compared with healthy controls (2.95±0.41) (P<0.05). A statistically significant increase in AFP levels was noted in patients with grade 3 NAFLD (5.43±1.51) when compared with grade 1 (2.92±1.06) and grade 2 NAFLD groups (3.97±1.45). Also, AFP was significantly higher in grade 2 NAFLD group than in grade 1 NAFLD group. AFP was correlated with NAFLD grade, but neither ALT nor AST showed correlation. According to multivariate analysis, correlation between NAFLD grade and serum AFP levels was independent from the other factors. Patients with NAFLD have higher AFP levels than those without fatty liver changes. AFP levels rise as grade of liver steatosis increases. NAFLD should be among the differential diagnosis of elevated serum AFP levels.