Clinical investigation of hepatopancreatobiliary and pancreatic disease

Introduction

The clinical approach to the patient diagnosed with hepatopancreatobiliary (HPB) disease must be systematic without neglecting clinical elements that could prove illuminating in the diagnostic process. The correct interpretation of symptoms and signs could be challenging, demanding great judgment, because even subtle clinical manifestations may forecast unattended events. A meticulous, detailed history and physical examination, followed by a few laboratory tests, are of great value. The clinical history should focus on the symptoms of HPB disease and their nature and pattern of onset and progression as well as potential risk factors. The modern and almost ubiquitous availability of second-level radiologic or endoscopic investigations must not subtract the physician from the analytical approach to the patient; “scan first, clinic later” must be avoided.

This chapter describes the common symptoms and signs of HPB disease, the value of basic investigations, and how this initial assessment guides further management. Clinical presentations and investigations of specific HPB diseases are also detailed.

Liver disease

The liver is an organ with a broad set of critical biologic functions, a unique dual vascular supply, and several distinct cell types that contribute to its physiologic functions and its potential pathology. Liver disease encompasses infectious, malignant, and chronic disease processes arising from a wide range of etiologies, which generally present with a few clinical patterns classified as hepatocellular, cholestatic, or mixed. In hepatocellular diseases (e.g., steatosis, alcoholic liver disease [ALD], and viral hepatitis), the clinical and biochemical scenario is dominated by liver damage, inflammation, and necrosis. In cholestatic diseases (e.g., bile duct—gallstones or malignant—obstruction, biliary cirrhosis), bile flow obstruction predominates. In the mixed form, both characteristics are present.

The results from the last Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) on the burden of chronic liver disease (CLD) revealed that globally in 2017, cirrhosis caused more than 1.32 million deaths (66.6% in males) compared with less than 899,000 deaths in 1990. These deaths constituted 2.4% of all deaths, with an age-standardized death rate of 16.5 per 100,000 population, which was at its lowest in the high-income countries and at its highest in sub-Saharan Africa. Globally, 31.5% of cirrhosis deaths in males were caused by hepatitis B, followed by alcohol-related liver disease (27.3%), hepatitis C (25.5%), nonalcoholic steatohepatitis (NASH; 7.7%), and other causes (8.0%). In females, hepatitis C (26.7%) was the leading cause, followed by hepatitis B (24.0%), alcohol-related liver disease (20.6%), NASH (11.3%), and other causes (17.3%). However, the scenario of CLDs in the United States has changed over the past 30 years. Hepatitis C is decreasing, whereas hepatitis B and alcohol-related liver disease remain stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing alongside the epidemic of obesity and type-2 diabetes mellitus (T2DM). In 2014, in the United States, the average yearly healthcare expenses in patients with CLD was $19,390 dollars, with nationwide healthcare expenses estimated at $29.9 billion (2.6% of the total nationwide for adults; see Chapters 68 , 69 , and 74 ).

Many patients come to the clinician’s attention not because of complaints of symptoms but because of the alteration of biochemical liver enzyme (aminotransferases) or function test results (prothrombin time/INR [PT/INR], bilirubin, and albumin) as part of routine physical examination or screening blood tests. Almost 10% to 17% of patients with unexplained liver enzyme elevation have previously unsuspected CLD. Clinicians should be able to accurately and efficiently recognize CLD given the high prevalence of morbidity associated with the liver tests and their significant costs and the consequences associated with cirrhosis. The patient evaluation path should lead to the determination of the etiologic diagnosis, severity (grading), and stage of disease.

Clinical history

The physician should begin the history by focusing on the symptoms of liver disease (the nature, pattern of onset and progression) and on potential risk factors to provide clues toward the underlying etiology of liver injury, which may help to differentiate acute injury from CLD. The duration of liver injury, particularly in the absence of symptoms, is not always certain. The clinical history should then proceed with a systematic inquiry into family history, drug history, social circumstances, employment, and travel. Commonly, it is the set of symptoms and the way in which they have arisen, rather than a specific symptom, that directs the determination of etiology.

Presenting symptoms may include abdominal discomfort, anorexia, nausea, vomiting, fatigue, malaise, fever, rash, itching, or jaundice.

Fatigue (described as lethargy, weakness, malaise, an increased need for sleep, or a loss of energy) is the most common and characteristic symptom. Typically, fatigue arises after exertion and is often intermittent and variable in severity. Abdominal pain is a common presenting symptom to be investigated for site, severity, radiation, and the rapidity of onset. Localization in the right upper quadrant, because of the distention or irritation of the richly innervated Glisson capsule, is usually marked by tenderness over the liver area. Severe pain may also indicate gallbladder disease, liver abscess, veno-occlusive disease, or acute hepatitis. A history of weight loss may point to a malignant process. Nausea and vomiting should be recorded along with a history of itching, jaundice, and the color of urine and stools. Jaundice is the hallmark symptom of liver disease and is best detected by the examination of the sclera or the mucous membranes below the tongue. The loss of functioning hepatocellular mass leads to hypoalbuminemia, which can manifest as a shortness of breath, ankle swelling, abdominal distension, and ascites, all of which can occur in many acute and chronic HPB disorders. Gastroesophageal varices and splenomegaly are consequences of portal hypertension and can clinically manifest as hematemesis or melena, thus requiring urgent endoscopic investigation. The increased peripheral conversion to estrogen resulting from the decreased hepatic metabolism and catabolism of androstenedione results in palmar erythema, spider nevi, gynecomastia, decreased body hair, and testicular atrophy. Terry nails (white nails) are characterized by a silver-white pallor that can range from the proximal to the entire nail bed, obscuring the nail lunula.

Accurate recording of alcohol intake is important in assessing the cause of liver disease, focusing on whether alcohol abuse or dependence is present (the CAGE questionnaire is recommended) and on planning management and treatment because heavy alcohol use impacts CLD outcomes.

A past medical history should be obtained and include any major illnesses and any abdominal surgery. A record of comorbidities and exercise tolerance should be made because this will guide the surgeon in assessing fitness for future intervention if required.

Physical examination

A physical examination is a fundamental complement to, rather than a substitute for, diagnostic investigations. Indeed, physical signs need to be used with additional clinical criteria to augment the probability of identifying patients with CLD. Physical signs are generally of low sensitivity for the diagnosis, and signs with higher specificity are associated with clinically decompensated disease. Typical findings in CLD are: jaundice ( Fig. 12.1 ), hepatomegaly ( Fig. 12.2 ), liver tenderness, splenomegaly, spider nevi, palmar erythema ( Fig. 12.3 ), and scratching injuries. Ascites, edema, sarcopenia, collateral circulation, hepatic fetor, and encephalopathy are signs of advanced disease. Signs related to alcohol abuse are gynecomastia ( Fig. 12.4 ), parotidomegaly, facial telangiectasia, Dupuytren contracture, and testicular atrophy (see Chapters 74 , 76 , and 77 ).

When inspected under natural light, jaundice can be noted within the sclera or the mucous membranes below the tongue. Jaundice can usually be observed when the bilirubin level is above 43 μmol/L (2.5 mg/dL). Hyperpigmentation is typical of advanced CLD, such as primary biliary cirrhosis and sclerosing cholangitis, whereas in hemochromatosis, pigmentation is slate-gray. Spider nevi are superficial, tortuous, arterial skin lesions with a central arteriole and numerous small radiating vessels ( Fig. 12.5 ). Usually found in the vascular territory of the superior vena cava (arms, face, and upper torso), more than two or three is likely to be abnormal. Palmar erythema may also develop in healthy individuals and is frequently found during pregnancy. Hippocratic fingers (clubbing; Fig. 12.6 ), white nails (Terry nails), koilonychia ( Fig. 12.7 ), and asterixis are all features of CLD. During eye examination attention should be paid to the pallor, scleral icterus, xanthelasma, and Kayser-Fleischer rings. Physical findings of hepatic encephalopathy include asterixis and flapping tremors of the body and tongue. When there is a portal-venous shunt, a characteristic fruity, ammoniacal, odor—called fetor hepaticus —occurs because of exhaled thiols. During abdominal examination, particular attention should be paid to any scars from previous abdominal surgery, abdominal distension, and areas of discoloration. Ascites ( Fig. 12.8 ) is appreciated by detecting shifting dullness by careful percussion. Portal hypertension may present with cutaneous manifestations such as visible collateral veins radiating from the umbilicus called caput medusae ( Fig. 12.9 ).

Palpation of the abdomen should begin with a general light palpation, looking for obvious masses and areas of tenderness. The healthy liver is usually impalpable. Reduction in liver size is also important because this may occur in cirrhosis and certain types of hepatitis. A lobe may undergo hypertrophy and become palpable, and this may occur in the presence of hemiliver atrophy or after liver resection. Marked hepatomegaly is typical of cirrhosis, veno-occlusive disease, infiltrative disorders such as amyloidosis, metastatic or primary cancers of the liver, and alcoholic hepatitis. Careful assessment of the liver edge may also reveal unusual firmness, the irregularity of the surface, or frank nodules. A hard, knobby liver often indicates the presence of metastases, whereas smooth enlargement may be because of cirrhosis.

Causes of hepatomegaly are listed in Box 12.1 .

Splenomegaly may occur in many medical conditions. Splenomegaly can be difficult to find but is significant in liver disease. Percussion may be useful, and if ascites is present, the spleen may be ballotable. If the spleen is sufficiently enlarged, the notch on its anterior border may become palpable ( Fig. 12.10 ).

Causes of splenomegaly are listed in Box 12.2 .

Clinical features of liver disease