Diagnosis Of Nonalcoholic Fatty Liver Research Articles

A Paradigm Shift in the Outpatient Approach to Liver Function Tests

The American Gastroenterological Association (2002), Canadian Medical Association (2005), and the Centers for Disease Control and Prevention (2006) released guidelines to screen patients with mild elevations of liver enzymes for hepatitis B and hepatitis C. Mildly elevated liver enzymes were defined as less than five times the upper limit of normal, but above the normal reference range. The rationale for this recommendation was based on many factors including cost effectiveness, lab variation, and ultimately, for better patient care.Chronic hepatitis B and C have values of transaminases that fluctuate between normal and mildly abnormal. Screening patients with even mild elevations of transaminases allows many chronic hepatitis patients to be diagnosed early in the course of their disease. Diagnosing these patients early in their disease course leads to better treatment response, decreased progression to cirrhosis, lower viral loads leading to decreased incidence of extrahepatic manifestations, prevention of hepatocellular carcinoma, and decreased likelihood of liver transplantation.There are organizations which recommend discontinuing hepatotoxic medications such as acetaminophen or nonsteroidal anti-inflammatory drugs and reevaluating the patient in three months. However, this recommendation misses a number of hepatitis patients for the reasons aforementioned. The obesity epidemic has clouded the diagnosis of hepatitis B/C as patients that have obesity, diabetes mellitus, and metabolic syndrome are not being screened due the presumptive diagnosis of nonalcoholic fatty liver disease.Not screening patients in the setting of obesity is not cost-effective and also leads to increased morbidity, as we will discuss in this manuscript. Additionally, it has been proven in the literature that it is more cost-effective to screen for hepatitis B/C in high-prevalence areas, than to reassess the patient months later, and potentially miss a diagnosis of hepatitis B/C. The overall goal of this study is to increase screening awareness of patients with mild transaminitis elevations through publication in order to diagnose patients with hepatitis B and C prior to the development of chronic liver disease.

Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA and many other parts of the world. Its prevalence continues to rise; currently affecting about one in four adults and 10% of children in the USA. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, no-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Currently, the diagnosis of NASH requires an invasive liver biopsy with drawbacks of sampling and interpretation error. Clinical risk factors for NASH include diabetes and the metabolic syndrome; however, these are not sufficiently predictive of the condition by themselves. Routine liver enzyme levels are not reliable; however, novel plasma hepatocyte cell death markers either alone or in combination with clinical risk factors are potential non-invasive diagnostic tools for the future. This review provides a concise overview of the role non-invasive diagnostic tools for the differentiation of fatty liver from NASH as well as for the determination of presence and extent of fibrosis.

Nonobese Population in A Developing Country Has A High Prevalence of Nonalcoholic Fatty Liver and Significant Liver Disease

There is a paucity of community-based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength. We conducted a prospective epidemiological study comprising a 1:3 subsample of all adult (>18 years) inhabitants of a rural administrative unit of West Bengal, India. Subjects positive for hepatitis B virus and/or hepatitis C virus infection and consuming any amount of alcohol were excluded. Diagnosis of NAFL was by dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The risk factors of having NAFL were analyzed. A total of 1,911 individuals were analyzed, 7% of whom were overweight and 11% of whom had abdominal obesity. The prevalence of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%, respectively. Seventy-five percent of NAFL subjects had a body mass index (BMI) <25 kg/m(2), and 54% were neither overweight nor had abdominal obesity. The subjects with the highest risk of having NAFL were those with a BMI >25 kg/m(2) (odds ratio 4.3, 95% confidence interval 1.6-11.5). Abdominal obesity, dysglycemia (fasting plasma glucose >100 mg/dL or elevated homeostatic model assessment of insulin resistance), and higher income were the other risk factors. Even having a normal BMI (18.5-24.9 kg/m(2)) was associated with a 2-fold increased risk of NAFL versus those with a BMI <18.5 kg/m(2). There is a significant prevalence of NAFL and potentially significant liver disease, including cryptogenic cirrhosis, in this predominantly nonobese, nonaffluent population in a developing country. NAFL will be a major determinant of future liver disease burden in countries of the developing world.

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non-alcoholic fatty liver disease. C57BL/6, KK-Ta and KK-Ay mice were fed a high-fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor-alpha. Serum levels of OCT increased in KK-Ay fed a high-fat diet compared with the normal diet-fed group, whereas C57BL/6 and KK-Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor-alpha was significantly elevated in ob/ob mice, but not in db/db mice. Serum OCT seemed to reflect tumor necrosis factor-alpha-mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non-alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes.

P.424 Metformin in the treatment of non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH.

Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease

Nonalcoholic fatty liver disease has been defined by the presence of hepatic steatosis in the absence of other chronic liver diseases. We sought to determine whether obesity, insulin resistance, and the metabolic syndrome, which are the main risk factors for nonalcoholic fatty liver disease, are associated with similar elevations in serum alanine aminotransferase activity in persons with and those without other causes of chronic liver disease. Adult participants of the third National Health and Nutrition Examination Survey were divided into those with causes of chronic liver disease (n = 1037), defined as viral hepatitis, excessive alcohol consumption, or increased transferrin-iron saturation, and those without (n = 8004). Among persons with other causes of chronic liver disease, obesity (adjusted odds ratio, 4.9; 95% confidence interval, 2.5-9.4), insulin resistance (adjusted odds ratio, 6.8; 95% confidence interval, 3.0-15.5, comparing the highest and the lowest quartile), and the metabolic syndrome (adjusted odds ratio, 3.3; 95% confidence interval, 1.4-8.0) were all strongly associated with increased alanine aminotransferase activity (>43 IU/L). Among persons without other causes of chronic liver disease, statistically similar associations were identified. Obesity, insulin resistance, and the metabolic syndrome are strong predictors of increased alanine aminotransferase activity in the US population, both in persons with and in persons without other causes of chronic livers disease. We hypothesize that metabolic fatty liver disease related to these conditions is the cause of the increased alanine aminotransferase activity and may be underrecognized in persons with other causes of chronic liver disease.

P0038 PP NON ALCOHOLIC FATTY LIVER AND INSULIN RESISTANCE IN OBESE ADOLESCENTS

Introduction: The insulin resistance syndrome is composed for several clinical and laboratory findings, the list of the different affections that it produces are continuous increasing every day. Obesity is the predominant factor that leads to insulin resistance and secondary hyperinsulinemia. It has been state that the non-alcoholic fatty liver (NAFL) in obese patients is mainly due to this secondary hyperinsulinemia. The purpose of our investigation was to know if the adolescent obese patients with NAFL showed a great insulin resistance in relationship with the adolescent obese patient who didn’t have this liver disease. Methods: 40 obese adolescents aged 10–16 years (18 males and 22 females) were studied, 20 with NAFL and 20 without this liver disease. All the patients had a Body Mass Index above of the 90 percentile for sex and age, and had a moderate obesity (130 a 139% of weight for height) or severe (above the 140%). We obtain from the medical records the antecedents of familiar type 2 diabetes mellitus (type 2 DM). The diagnosis of NAFL was performed by the echography, that shown the presence of diffuse echogenic liver. Oral Glucose Tolerance Test (OGTT) were made in all patients (fasting and 120 minutes), blood was drawn for measurements glucose concentration (glucose oxidase methods) and insulin (by radioinmunoassay). The statistical method was the “students t”(p Đ 0,05) Results: Edit help It was observed that the mean fasting and 120 minutes glucose concentration of the obese patients with NAFL were not at different of the obese without it (p >0.05). In all the obese patients the fasting insulin levels were no different but at 120 minutes of OGTT it was higher in the NAFL patients (p<0,05). The NAFL groups shown a higher familiar frecuency of type 2 DM (18%) when they were compared with the group without the liver disease (6%). Conclusion: We found out that the obese patient with NAFL shown the higher levels of hyperinsulinemia due to a greater insulin resistance and we point out that this is a risk factor of suffering the liver disease, that is part of the insulin resistance syndrome. It was also more evident in the obese group with NAFL a familiar antecedents of type 2 DM and this is another risk to develop this syndrome.

Pathologic features associated with fibrosis in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH.