Patrick Louis Brine September 27 th Associate Program Director SEHC IM Residency Assistant Professor Northeast Ohio Medical University Clinical Adjunct Professor Lake Erie College of Osteopathic Medicine Clinical Adjunct Professor Ohio University Heritage College of Osteopathic Medicine Identify presence of elevated liver enzymes in otherwise healthy patients in outpatient medicine Become familiar with differential diagnoses of elevated liver enzymes Introduce algorithmic approach to evaluation of elevated liver enzymes Identify most common etiology of elevated liver enzymes in the asymptomatic patient Be aware of current treatment guidelines for NAFLD Introduce current HCV guidelines for appropriate screening and treatment 1
Estimated 8.9% of patients have elevated liver enzymes without the presence of symptoms in a survey from 1999-2002.¹ Single isolated, mildly elevated liver enzyme value may lead to costly, anxiety-provoking, and risky extensive evaluation² ¹Ioanou GN, Boyko EJ, Lee SP. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999-2002. Am J Gastroenterol 2006; 101:76-82. ²Aragon, George and Zobair M Younossi. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. CCJM 2010; 77(3): 195-204. Patient s overall health? Underlying chronic illness Duration and Pattern of Enzyme Elevation Patient Characteristics/Demographics Age Personal or family history of liver, lung, or neurologic disease Risk factors for viral hepatitis Alcohol consumption Prescribed and OTC medications Risk/Benefit Ratio Evaluate Cost 2
High AST/ALT- suggest liver cell damage Markers in several organs but highest levels in liver Elevated Alkaline Phosphatase- suggest cholestasis Liver and Bone origin GGT is not specific Most sensitive marker of hepatobiliary disease Utilize in presence of elevated Alk Phos level Hepatocellular Diseases (Aminotransferase Elevation Predominate) NAFLD Chronic Viral Hepatitis Genetic Hemochromatosis (Northern European ethnicity) Alcoholic Liver Disease Medication Toxicity Wilson s Disease Alpha-1- Antitrypsin Deficiency Cholestatic Diseases (Alkaline Phosphatase and GGT Elevation Predominate) PBC PSC Neoplasm Biliary Obstruction (gallstones, etc) Drug Hepatotoxicity Autoimmune Cholangiopathy Sarcoidosis CCJM 2010 3;77(3):195-204. 3
Hepatocellular Abnormalities Cholestatic Abnormalities Drug-Induced Fatty Liver Acetaminophen- acute hepatitis Amoxicillin-Clavulanate (other PCNs) Amiodarone Allopurinol- granuloma Anabolic Steroids Corticosteroids Azathioprine- veno-occlusive disease, nodular regenerative hyperplasia Captopril Tetracycline Diclofenac (NSAIDs) Chlorpromazine Valproic Acid Hydralazine- granuloma Isoniazid Methotrexate- fibrosis Methyldopa Nitrofurantoin- autoimmune like disease Quinidine- granuloma Erythromycin Estrogens Oral Contraceptives Phenytoin- mononucleosis like syndrome Carbamezapine Sulfa drugs Statins CCJM 2010 3;77(3):195-204. CCJM 2010 3;77(3):195-204. 4
CCJM 2010 3;77(3):195-204. Most evaluations can be completed by the Primary Care Physician Input from Gastroenterology or Hepatology are valuable when the initial work-up fails to establish diagnosis Also valuable to assure effective therapy for a specific disease REASSURANCE, PATIENT EDUCATION, and SYSTEMATIC APPROACH for evaluating these abnormalities can identify most treatable causes in the most cost effective and efficient manner¹ CCJM 2010 3;77(3):195-204 5
Spectrum of disease: simple steatosis nonalcoholic steotohepatitis cirrhosis Prevalence- 30% in general US population¹ 50-60% in Type 2 DM 90-95% in Morbid Obesity Only 5% of these patients progress to Steatohepatitis Risk Factors: components of metabolic syndrome- which also increase risk for development of Steatohepatitis Abdominal obesity Diabetes (insulin resistance) Hyperlipidemia (High TGs and Low HDL) Hypertension Medications Treatment of underlying risk factors ¹Rinella, Mary E. Nonalcoholic Fatty Liver Disease. JAMA 2015; 313(22):2263-2273. Noninvasive Assessment U/S is sensitive but limited to steatosis >33% for diagnosis More testing biomarkers are under review to increase sensitivity 6
Lifestyle Intervention- weight loss Body weight loss is associated with improvement in NAFLD characteristics with biomarkers and imaging¹ Diet- Mediterranean diet has been studied Exercise Bariatric Surgery should be considered for those who cannot lose weight Pharmacological Treatment No FDA approved treatments- currently being studied Statin use with NAFLD- appear to be safe- no improvement in progression of disease Consider in patients who have increased serum cholesterol levels Cardiovascular disease is leading mortality in NAFLD patients ¹Eckard C, Cole R, Lockwood J, et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol. 2013; 6(4): 249-259. Approximately 2.2 million to 3.2 million Americans are infected with HCV Roughly ½ of those are unaware CDC & USPTSF: one-time HCV test is recommended in asymptomatic persons in the 1945-1965 birth cohort and other persons based on exposures, behaviors, and conditions that increase risk for HCV infection persons in the 1945 to 1965 birth cohort accounted for nearly three-fourths of all HCV infections Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. Volume 62, Issue 3 September 2015 Pages 932 954 7
. Birth cohort Persons born between the years of 1945 and 1965 2 Risk behaviors Injection-drug use (current or ever, including those who injected once) Intranasal illicit drug use 3. Risk exposures Long-term hemodialysis (ever) Getting a tattoo in an unregulated setting Health care, emergency medical, and public safety workers after needlesticks, sharps, or mucosal exposures to HCV-infected blood Children born to HCV-infected women Prior recipients of transfusions or organ transplants, including persons who were notified that they received blood from a donor who later tested positive for HCV infection received a transfusion of blood or blood components or underwent an organ transplant before July 1992 received clotting factor concentrates produced before 1987 were ever incarcerated 4. Other HIV infection Unexplained chronic liver disease and chronic hepatitis including elevated ALT levels Solid organ donors (deceased and living Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology Volume 62, Issue 3 September 2015 Pages 932 954 All persons recommended for HCV testing should first be tested for anti-hcv using an FDAapproved test. Positive results should be confirmed by nucleic acid testing for HCV RNA Evaluation by a practitioner who is prepared to provide comprehensive management, including consideration of antiviral therapy, is recommended for all persons with current (active) HCV infection Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. Volume 62, Issue 3 September 2015 Pages 932 954 8
Antiviral treatment is recommended for all patients with chronic HCV infection, except those with limited life expectancy due to non-hepatic causes. If resources limit the ability to treat all infected patients immediately as recommended, then it is most appropriate to treat those at greatest risk of disease complications before treating those with less advanced disease Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus:hepatology Volume 62, Issue 3 September 2015 Pages 932 954 Aragon, George and Zobair M Younossi. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. CCJM 2010; 77(3): 195-204. Ioanou GN, Boyko EJ, Lee SP. The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999-2002. Am J Gastroenterol 2006; 101:76-82. Rinella, Mary E. Nonalcoholic Fatty Liver Disease. JAMA 2015; 313(22):2263-2273. Eckard C, Cole R, Lockwood J, et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol. 2013; 6(4): 249-259. 9
Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. Volume 62, Issue 3 September 2015 Pages 932 954 10