Janice is a 45yo Caucasian female with symptoms of Non Alcoholic Fatty Liver Disease.Her BMI is 40 and she was diagnosed with DM type 2 3 years ago. Her last HgbA1c was 7.4. She lives a sedentary life style. She state she has significant fatigue and but is otherwise asymptomatic. What diagnostics would you order for Janice? Why? What treatment plan would you recommend for her? What is her prognosis?
NPR1115_Cover_Puneet.indd 36 The Nurse Practitioner • Vol. 40, No. 1 www.tnpj.com36 The Nurse Practitioner • Vol. 40, No. 11 www.tnpj.com nonalcoholic Treating the patient with Ill us tra tio n by H ob bi t / S hu tte rs to ck © Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.tnpj.com The Nurse Practitioner • November 2015 37 onalcoholic fatty liver disease (NAFLD) covers a wide spectrum of fatty liver issues, ranging from simple fatty infi ltration in liver cells (hepatocytes) to nonalcoholic steatohepatitis (NASH), to cirrhosis and/ or hepatocellular carcinoma (HCC).1 With the increasing prevalence of obesity, type 2 diabetes mellitus, and metabolic syndrome, the prevalence of NAFLD is also increasing, and NPs will be caring for these patients more frequently.2 This article seeks to improve the understanding of the spectrum of NAFLD and provide up-to-date treatment recommendations. ■ Background and prevalence of NAFLD NAFLD is defi ned as biopsy- or imaging-proven hepatic steatosis, in which other causes of fatty liver have been excluded, including alcoholic liver disease, genetic diseases, or medication-related causes.3,4 (See Defi nition of signifi cant alcohol consumption.) NAFLD should be considered as a diagnosis in patients who have had other causes of liver disease excluded and who have one or more risk factors for NAFLD (see Risk factors for development of NAFLD). Ninety percent of patients with NAFLD have one or more of the following risk factors: obesity, insulin resistance, met- abolic syndrome, type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidemia, elevated triglyceride levels, and/or low high-density lipoprotein levels.3-5 The prevalence of NAFLD is approximately 20% world- wide and 25% in Western countries, making it one of the most common causes of liver disease.2-4,6 NAFLD occurs in one in three individuals in the devel- oped world and is more common in patients with severe obesity and diabetes.3,7,8 Mortality and disease evolution to fi brosis or cirrhosis is increased in older patients with NAFLD.3 Cardiovascular disease-related events are the most common causes of mortality in patients with NAFLD.3 NASH, which is a pro- gression from simple fatty liver disease to infl ammation and injury, is the third most common cause of liver disease requiring a liver transplant in the United States.3,4,7 According to Charlton and colleagues, by 2020, NASH will be the leading cause of liver transplant in the United States.9 Patients with NASH can progress to cirrhosis and/or HCC. ■ Pathophysiology of NAFLD The pathophysiology of NAFLD is complex and not com- pletely understood. Day and James sought to describe the process of fatty liver disease progression as the “two hits By Amanda Chaney, MSN, ARNP, FNP-BC 2.0 CONTACT HOURS 1.0 CONTACT HOURS Keywords: lifestyle modifi cations, liver disease, nonalcoholic fatty liver disease Abstract: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide health crisis. It is important for NPs to understand the spectrum of NAFLD. Although lifestyle modifi cations are the fi rst-line treatment, the NP should be aware of current and future medication management to help the patient live a healthy life. N fatty liver disease Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. 38 The Nurse Practitioner • Vol. 40, No. 11 www.tnpj.com Treating the patient with nonalcoholic fatty liver disease theory.12” In the fi rst hit, steatosis, or fatty infi ltration in the liver, occurs from issues with insulin resistance and fatty acid metabolism.2,10-12 Increased free fatty acid to the liver causes hepatic steatosis. Insulin resistance increases lipolysis from adipose tissue. This process leads to release of proin- fl ammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin-6), oxidative stress, and infl ammation.13 These, along with molecular endotoxins and genetic factors, are thought to contribute to the second hit.2,4,14,15 The second hit results in oxidative stress and steatohepatitis.12 Dietary choices can also play a part. With high amounts of cholesterol to the liver (either from diet or genetics), fatty acids are converted to nontriglyceride metabolites. These particles contribute to hepatocyte injury. High con- sumption of sugar—particularly fructose—reduces intracel- lular adenosine triphosphate and is converted to fat, which is deposited in the liver.5 Collagen is deposited in the liver and causes fi brosis as infl ammation and liver injury occur.4 As this process continues, fi brosis can turn into cirrhosis and/or HCC. As the hepatocytes become fatty, patients are at higher risk for developing diabetes mellitus, cardiovas- cular disease, and complications related to these diseases.7 ■ Diagnosing NAFLD It may be diffi cult to know when to suspect NAFLD, since most patients are asymptomatic.4,5,7 Some symptoms that present are vague, including abdominal discomfort, fatigue, and nausea.2 Higher-risk patients include patients who have type 2 diabetes mellitus and who are obese. These patients are not only at higher risk for liver disease progression but also cardiovascular disease and death.7 There is currently no diagnostic screening tool or recommendations for screening for NAFLD in primary care, even if a patient has several risk factors to suggest this disease.3 In most cases, NAFLD is found incidentally when a patient has elevated liver enzymes or when it is seen on radiologic imaging stud- ies as hepatic steatosis.2,4 History. A complete history should be obtained in the patient who has liver disease when NAFLD is suspected. Occasional symptoms that may occur include right upper quadrant abdominal pain, pruritus, and jaundice. Gener- ally, the patient is without symptoms. Other etiologies of liver disease should be excluded. Current lifestyle and dietary habits, including alcohol consumption history, should be noted. Social history should include current or prior intra- vascular or other illicit drug use, blood transfusions, and sexual activity.4 Physical exam. Physical exam should include vital signs, height, weight, body mass index (BMI), BP, and waist cir- cumference. Hepatosplenomegaly may be present if the patient has evidence of portal hypertension.2,4 Dorsocervi- cal lipohypertrophy, an increased amount of fat distribution along the cervical spine, may be present and has been noted in patients with NASH.16 Lab fi ndings. Labs to exclude other causes of liver disease include: total protein, alanine aminotransferase (ALT), as- partate aminotransferase (AST), alkaline phosphatase, albu- min, total bilirubin, hepatitis B surface antigen, hepatitis C antibody, ferritin, iron, fasting blood glucose, hemoglobin A1C, lipid panel, and low-density lipoprotein cholesterol, prothrombin time, and insulin levels.4 Patients with NAFLD commonly have elevated ferritin levels, and 20% have elevated uric acid levels.2,3 Most patients with NAFLD will have a mild elevation of AST and ALT, although some will be normal.2 There are no imaging or biomarker tests that can differentiate between hepatic ste- atosis and NASH.8 Cytokeratin-18 fragment levels are the most researched tool to predict NASH, which is an indicator of hepatocyte apoptosis.7 Radiologic fi ndings. Imaging studies to evaluate for NAFLD could include ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). Ultrasound cannot identify infl ammation or fi brosis, but it is the fi rst imaging study done to evaluate for hepatic steatosis, for which it has a sensitivity of 60% to 94% and specifi city of 66% to 97%.4,7 It is inexpensive and extensively available. CT scan can be done to assess the structure of the liver.4 It is an option for determining hepatic steatosis; however, there is signifi cant radiation associated with this imaging study.7 MRI is accurate for quantifying the extent of hepatic steato- sis, but it is expensive.4 Magnetic resonance spectroscopy is accurate in identifying steatosis and has the potential to become an ideal test for grading and determining the Defi nition of signifi cant alcohol consumption3 Men Greater than 21 drinks per week over a 2-year period Women Greater than 14 drinks per week over a 2-year period 1 drink = ~10 g alcohol Risk factors for development of NAFLD3,4,8 • Age, older than 45 • Diabetes mellitus • Hispanic ethnicity • Portal hypertension • Insulin resistance • Metabolic syndrome • Obesity • Family history signifi cant for metabolic syndrome, cardiovascular disease, chronic liver disease Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Treating the patient with nonalcoholic fatty liver disease www.tnpj.com The Nurse Practitioner • November 2015 39 presence of steatosis; however, it is costly and with limited availability.7 Noninvasive measures. Risk scores, such as the NAFLD fi brosis score and the NASH test, have been used to try to determine patients who have NASH but can be inaccu- rate (see Noninvasive fi brosis scoring tools).5,17-19 Transient elastography is a newer imaging study on the hori- zon. Described as a pulse-echo ultra- sound, it has shown usefulness in determining the presence of fi brosis. This may be helpful in determining if liver biopsy is necessary.7 Liver biopsy. Liver biopsy is the gold standard for determining if NAFLD is present and for staging severity of disease.7 Complications, including bleeding and infection, occur in 1% to 3% of patients; death occurs in 0.01% of patients.7 Misdiagnosis can occur in many cases. Staging and diagnosis are subjective and can vary by the pathologist.7 Additionally, there is a higher risk of complica- tion and diffi culty obtaining an adequate sample in patients who are obese.7 A liver biopsy should be considered in patients with highly elevated liver function tests (LFTs) or patients with elevated LFTs and a normal BMI.4 The pathology report may include fi ndings indicative of NAFLD such as: Mallory hya- line, hepatocyte ballooning, and lymphocytic and neutro- philic infl ammatory infi ltrate in perivenular areas. Other fi ndings may state hepatocyte necrosis, apoptosis, and degree of fi brosis—graded and staged.4,8 ■ NAFLD treatment options Patients with NAFLD without liver injury have an excellent prognosis, and their management is primarily aimed at prevention and reversal of hepatic injury and fi brosis.3-5 The aim is to prevent progression to cirrhosis and