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History Taking and Physical Examination for the Patient with Liver Disease Esperance A BLBK700-c01 BLBK700-Schiff July 29, 2017 2:54 Printer Name: Trim: 279mm × 213mm PART I Overview: Clinical Fundamentals of Hepatology COPYRIGHTED MATERIAL BLBK700-c01 BLBK700-Schiff July 29, 2017 2:54 Printer Name: Trim: 279mm × 213mm BLBK700-c01 BLBK700-Schiff July 29, 2017 2:54 Printer Name: Trim: 279mm × 213mm 3 CHAPTER 1 History Taking and Physical Examination for the Patient with Liver Disease Esperance A. Schaefer1 & Lawrence S. Friedman2 1Harvard Medical School and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA 2Harvard Medical School, Tufts University School of Medicine, Department of Medicine, Newton-Wellesley Hospital, and Massachusetts General Hospital, Newton and Boston, MA, USA Key concepts r The history and physical examination may provide clues to the decreased body hair, gynecomastia, and palmar erythema are r presence of liver disease in a person thought to be healthy. r associated with cirrhosis with a specificity of 89–97%. In a patient undergoing evaluation for liver disease, the history and Assessment of liver span, tenderness, and contour provides important physical examination help determine the underlying cause of liver clinical information. Liver span is best assessed by percussion or the injury, presence or absence of advanced hepatic fibrosis, and evidence “scratch test.” In general, the normal liver span is less than 12 cm in r of clinical complications of cirrhosis and portal hypertension. r the midclavicular line, and the edge is smooth and nontender. Common causes of liver injury in patients with liver disease of For the patient with established cirrhosis, careful attention should be unknown cause include nonalcoholic fatty liver disease (NAFLD), paid to vital signs. A reduced mean arterial pressure is associated with alcoholic liver disease, hepatitis C, and drug-induced liver injury. The renal impairment, particularly when the mean arterial pressure drops patient should be assessed carefully for excessive alcohol intake, new below 82 mmHg. Weight gain raises concern for the development of medication or herbal and dietary supplement use, risk factors for fluid retention and ascites, and weight loss may be associated with r hepatitis C, and evidence of metabolic syndrome. r malnutrition or malignancy. In a patient with known liver disease, clinical evaluation for advanced Ascites may be suspected on physical examination by the detection hepatic fibrosis has particular importance, because one third of of flank dullness, bulging flanks, shifting dullness, and a fluidwave. patients who present for an outpatient hepatology evaluation already Flank dullness and bulging flanks have a sensitivity of at least 80% r have underlying cirrhosis. but a specificity of only 59% for detecting ascites. The skin examination is helpful when assessing a patient for advanced hepatic fibrosis; Terry’s nails, spider telangiectasias, The liver is an organ with a broad set of critical biologic of parenchymal cells and, in health, are the primary site of functions, a unique dual vascular supply, and several dis- vitamin A storage. In the setting of chronic inflammation, tinct cell types that contribute to its physiologic functions however, stellate cells are responsible for the deposition as well as potential pathology. Most of the key functions of extracellular matrix that leads to cirrhosis. The process of the liver are carried out by the hepatocytes, which of progressive hepatic fibrosis, in general, proceeds over are the most abundant cell type in the liver. Hepatocytes a timeframe of years to decades. This slow progression are responsible for drug detoxification, protein synthesis allows effective intervention if liver disease is identified (including albumin and coagulation factors), excretion of and treated early in its clinical course. Unfortunately, bile for digestion, and synthesis of cholesterol and fatty chronic liver injury is often asymptomatic, and symptoms acids. Injury to hepatocytes and the pursuant inflam- and signs may not manifest until advanced fibrosis or mation may occur from a toxin-mediated insult such as decompensated liver disease has ensued. alcohol or medications, lipotoxicity as seen in fatty liver, In the evaluation of a patient with liver disease, the infectious causes such as viral hepatitis, or autoimmunity. focus of history taking and the physical examination Stellate cells are less abundant, comprising only about 5% will be guided by the reason for which the patient has Schiff’s Diseases of the Liver, Twelfth Edition. Edited by Eugene R. Schiff, Willis C. Maddrey and K. Rajender Reddy. © 2018 John Wiley & Sons Ltd. Published 2018 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/schiffsdiseasesoftheliver BLBK700-c01 BLBK700-Schiff July 29, 2017 2:54 Printer Name: Trim: 279mm × 213mm 4 Part I: Overview: Clinical Fundamentals of Hepatology presented and has been referred for consultation. Com- disease, α1-antitrypsin deficiency, and congestive hep- mon reasons for referral to a hepatologist include ele- atopathy, each accounted for <1% of new patient visits [2]. vated liver biochemical test levels, abnormal serologic Many patients with acute or chronic liver injury are test results, jaundice, known chronic liver disease, or evi- asymptomatic, and when symptoms do occur, they are dence of decompensated liver disease. For all of these often nonspecific. Presenting symptoms may include clinical scenarios, specific historical elements and physi- abdominal discomfort, anorexia, nausea, vomiting, cal examination findings may provide important insights fatigue, malaise, fever, rash, pruritus, or jaundice. Careful into the ongoing disease process. In general, the clinician questioning about risk factors for certain conditions can seeks, through history taking and physical examination, provide insight into the likely nature of the liver injury. to determine the (i) etiology of liver injury, (ii) presence Toxins, including alcohol and prescribed medications, or absence of advanced hepatic fibrosis, and (iii) existence are common causes of abnormal liver biochemical test lev- of clinical complications of cirrhosis and portal hyperten- els and chronic liver disease. DILI may occur from either sion. The clinical objectives are to identify the cause of prescription or over-the-counter medications, including injury and address it early in the disease course to prevent dietary and herbal supplements, and a careful medica- development of advanced hepatic fibrosis, and, if cirrho- tion history including prescription and nonprescription sis is already present, to monitor the patient carefully for medications, supplements, and herbal remedies should be complications of end-stage liver disease. obtained. DILI can present with either acute or chronic liver injury and can range in severity from mild hepati- tis or cholestasis to acute liver failure. The estimated inci- Abnormal liver biochemical test levels dence of DILI is 19.1 cases per 100 000 population, and or known liver disease DILI accounts for 10% of all cases of acute liver failure [3]. The most common classes of drugs implicated in DILI are History taking antimicrobial agents (most notably amoxicillin-clavulanic Acute and chronic liver injury has a broad spectrum of acid, isoniazid, and nitrofurantoin) and dietary and herbal clinical presentations, and patients present to medical supplements [4], but any class of drug may be responsible. attention for a wide variety of reasons. Many patients are In alcoholic liver disease, gender and the quantity of completely asymptomatic and come to medical attention alcohol use are the primary predictors of hepatic injury after a routine physical examination or life insurance test- and fibrosis. Gender is an important risk factor for clin- ing has demonstrated elevated liver biochemical test lev- ically significant alcoholic liver disease, with women els. Others, particularly those with acute hepatitis, may developing liver injury at lower levels of daily alcohol present with abdominal pain, nausea and vomiting, fever, consumption than men. The daily threshold of alcohol or jaundice. The duration of liver injury, particularly in the intake for the development of cirrhosis is 40–60 g of alco- absence of symptoms, is not always certain. Clues such as hol in men, but only 20 g in women. With one alco- the time of onset of symptoms, prior normal test results, holic drink defined as containing 14 g of ethanol (the and the presence of potential risk factors may help differ- amount contained in 5 ounces (150 mL) of wine, 12 ounces entiate acute injury from chronic liver disease. (360 mL) of beer, or 1.5 ounces (45 mL) of 40-proof alco- When evaluating a patient with abnormal serologic test hol), the risk of alcoholic liver disease in women is asso- results or a known history of a specific liver disease, the ciated with more than one drink daily, compared with at focus of history taking and the physical examination is least two drinks daily for men [5]. The amount and type of both to provide clues toward the underlying etiology of alcohol consumed, along with the duration of alcohol use, liver injury (if unknown) and to assess the patient for clin- should be carefully assessed to determine a patient’s risk ical evidence of advanced hepatic fibrosis. Central to this for alcoholic liver disease. Patients frequently underreport objective is an understanding of the most common causes the quantity of consumption, and obtaining additional of liver injury and chronic liver disease. A
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