Comprehensive Practical Hepatology

Patients without advanced or severe liver disease may not display any signs or symptoms specific for liver diseases. Careful record of medical history may play an important role in diagnosing these patients. More advanced liver disease may present with symptoms such as fatigue, pruritus, abdominal fullness, and/or muscle cramps. Jaundice, ascites, hepatomegaly, splenomegaly, dilated abdominal wall veins, asterixis (encephalopathy), spider angiomata, and palmar erythema on physical examination may also suggest advanced liver diseases.

Abnormalities in liver function tests (LFTs) may be caused not only by hepatic diseases but also by non-hepatic disorders, while normal values on LFTs do not exclude liver disease. Therefore, LFTs should be interpreted based on all information about the patient. Practically, classification of LFTs into hepatic synthetic function, hepatocellular injury, and cholestasis is important to interpret liver abnormalities and to identify the etiology of liver injury. Liver injuries can be divided into two categories, hepatocellular and cholestatic. These categories are helpful in diagnosing liver diseases and in understanding mechanisms of injury. The hepatocellular pattern is characterized primarily by increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, whereas the cholestatic pattern is characterized by increased alkaline phosphatase (ALP) and bilirubin levels. Identification of the pattern may narrow the possible causes of liver injury in a patient. Imaging tests, such as ultrasound, CT, and MRI, may be helpful in the final diagnosis of liver diseases.

Although acute liver injury shows spontaneous improvement in many patients, some require special treatment and can develop fulminant hepatic failure. The etiology of acute hepatitis and acute hepatic failure varies in different countries, making prompt diagnosis and determination of etiology important for determining prognosis and proper patient management. Liver transplantation should be considered for patients who develop fulminant hepatic failure.

Patients presenting with chronic liver injury should be classified as having hepatocellular, cholestatic or mixed injury, because classification can narrow the causes of injury, making history taking and physical examination more effective. Diagnosis of drug- and alcohol-induced liver injury depends on careful history taking. Most patients with chronic liver diseases are asymptomatic, and key examinations for the diagnosis of each disease should be performed in an effective order. Severity of liver injury is estimated by PT-INR and T-Bil. Patients at risk for transition to hepatic failure should likely be transferred to a transplantation center.

Because liver tumors are usually asymptomatic, they are frequently observed incidentally on imaging tests performed for other purposes. The most common types of liver tumors are cysts and hemangiomas, which do not require any treatment unless they are accompanied by infection, hemorrhage, or rupture. In contrast, primary liver cancer and metastatic liver tumors are usually found in patients at high risk during regular checkups or close examination. Other benign masses found in the liver often need CT, MRI, or even liver biopsy for a final diagnosis. Radiofrequency ablation has been shown effective in the treatment of hepatocellular carcinomas and liver metastases from colorectal cancer, with liver resection also effective for those tumors.

There are many possible causes of abnormal liver function test results, including viral hepatitis, alcohol consumption, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones, and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury based on screening serology and diagnostic imaging analysis, abnormal liver function test results may be due to systemic disease. In most of these patients, systemic disease should be the primary focus of treatment. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatment of the liver.

Systemic abnormalities are often seen in patients with liver diseases. Especially, cardiopulmonary or renal diseases complicated by advanced liver disease are sometimes serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to these abnormalities in the management of patients with liver diseases.

Various unique infections, including amebic and parasitic infections, are seen in the liver because of its characteristic anatomical features. History taking, including details of food, travel, and sexual behavior, is important for differential diagnosis. Imaging studies, such as X-ray, ultrasonography, and computed tomography, as well as serological tests are essential to make a definitive diagnosis. A delay in making a definitive diagnosis may adversely affect outcome, as specific therapy for each infection is required.

The liver is an essential organ involved in elimination of drugs and toxins. Any drug, including herbal remedies or dietary supplements, can be a causative agent for drug-induced liver injury (DILI). An aging society or requirement for advanced medical care with multiple medications may complicate the management of DILI, especially in developed countries. The possibility of developing DILI should always be considered when starting new drugs. The classification of DILI—hepatocellular, cholestatic, or mixed—is useful for management. Discontinuation of the causative drug is usually sufficient to manage patients with DILI, but liver injury may persist or progress even after the drug has been stopped, especially in cholestatic type DILI.

Patients with severe or advanced liver diseases have greater risks during surgery than healthy subjects, which must be assessed by hepatologists. Decreases in hepatic blood flow during anesthesia or surgery are associated with postoperative liver damage. The risk of surgery in patients with liver cirrhosis is assessed by the Child–Pugh grade or the Model for End-Stage Liver Disease score. The type of surgery is another factor affecting the risk of patients with liver disease, and cardiac surgery is associated with higher mortality in patients with cirrhosis than other type of operations.

The liver is the main organ of metabolism and elimination of drugs. Thus, decreased liver function may result in abnormally high concentrations of drugs in the body. Drug elimination by the liver could be afftected by the first-pass effect, hepatic metabolism, and biliary extraction, and decreased haptic blood flow or cytochrome P 450 enzyme activities may affect drug metabolism in patients with advanced liver cirrhosis.

Although the incidence of acquired liver diseases such as viral hepatitis or fatty liver is lower during infancy and childhood than in adults, congenital or metabolic disorders should be suspected in children with liver dysfunction. It should be noted that normal ranges of biochemical liver tests in children are different from those of adult subjects. Pediatric liver diseases may cause a life threatening event, such as kernicterus, intracranial hemorrhage, or metabolic derangements.

The population of elderly individuals is increasing, especially in developed countries. Reductions in organ function are more frequent in the elderly, complicating treatment of various conditions. Elderly individuals are more susceptible to severe liver injury, show a decrease in drug metabolism and are at greater risk of developing malignancies.

Several specific liver diseases, which may be serious and require specific therapy including immediate delivery, are incidentally found in pregnant women. Since some of these diseases may be serious or even fatal, prompt diagnosis and treatment are important to save both mother and baby. The effect on the fetus of drugs administered to pregnant women must be considered. Moreover, if the mother has an infectious disease, prophylactic procedures are needed to protect the fetus.

Excess body weight has become a problem, especially in most developed countries. Excess nutrition is harmful to the liver and causes liver diseases including nonalcoholic fatty liver disease and hepatic malignancies. A well balanced diet and adequate exercise can help maintain a healthy liver and prevent liver diseases induced by metabolic abnormalities. In contrast, infectious liver diseases such as viral hepatitis and their consequent cirrhosis and hepatocellular carcinoma can be prevented by prophylaxis, including adequate vaccination against viruses and patient education.

Patients with fulminant hepatic failure, decompensated cirrhosis, or hepatocellular carcinoma defined according to the Milan criteria (no single lesion greater than 5 cm or no more than three lesions, the largest ≤ 3 cm) are potential candidates for liver transplantation. The 5-year survival rate after liver transplantation is 70% to 80%.