At a minimum, schedule follow-up testing of asymptomatic patients with abnormal laboratory findings in no more than 6 months. Persistent ALT elevation in such patients is most commonly caused by major viruses, alcohol abuse, nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH).8 Nonalcoholic fatty liver is especially likely in patients with clinical and demographic risk factors—those who, like John M., suffer from obesity or diabetes, or both.
Ultrasound yields further information
Further screening should be limited to patients who continue to have abnormal test results for 6 months or more or have multiple risk factors. While biopsy is still considered the gold standard for diagnosing and staging chronic liver disease, it should be considered, according to the American Gastroenterological Association, only if ultrasound and other tests have not been helpful in reaching a diagnosis.9
Often, though, ultrasonography aids in diagnosis. In the case of John M., ultrasound revealed an enlarged liver with diffuse echostructural dyshomogeneity and signs of severe steatosis and mild splenomegaly, but no increase in portal vein diameter and no ascites. For asymptomatic patients with cirrhosis or an earlier stage of liver disease, ultrasound at 6-month intervals, combined with blood alpha-fetoprotein measurement, can be used to track disease progression and screen for hepatocellular carcinoma.10
Newer, noninvasive methods aid in diagnosis
Noninvasive means of evaluating the presence and extent of liver fibrosis and differentiating cirrhosis from noncirrhosis, developed in recent years, have been found to have positive predictive values greater than 85% to 90%.11 Transient elastography (FibroScan, London, England), which assesses liver stiffness, is 1 such method. Although it is often used successfully, however, morbid obesity, small intercostal spaces, and ascites limit the diagnostic capability of this medical device.12
Fibrosis can also be detected with the use of 1 or more algorithms—each testing blood samples for a different combination of serum surrogate markers for liver disease. Some widely used algorithms include the APRI (AST-to-platelets ratio index), the Fibrotest (aptoglobin, alpha-2 macroglobulin, apolipoprotein A1, gamma-glutamyl transpeptidase, and bilirubin), the Hepascore (bilirubin, gamma-glutamyl transpeptidase, haluronic acid, alpha-2 macroglobulin, age, sex), and the BARD (BMI, AST/ALT ratio, diabetes).
Hepatologists often use the results of ultrasonography, followed by transient elastography in conjunction with findings from 1 or more of these algorithms, to determine which patients are candidates for liver biopsy.11,12
Staging is crucial, with or without biopsy
The decision to perform a liver biopsy should be based on a number of factors, including the patient’s age, lifestyle, liver chemistry abnormalities, desire for prognostic information, and associated comorbidities.9 Despite the value of biopsy, it is a costly procedure with potentially serious side effects and risks—and not always accepted by patients. In a recent survey of 1177 primary care physicians in France, as many as 59% of patients with chronic hepatitis C refused to undergo liver biopsy; what’s more, 22% of the doctors surveyed shared the patients’ hesitancy.13 Whether patients refuse biopsy or it is deemed unnecessary because ultrasound and other noninvasive tests result in a probable diagnosis, staging is necessary, both to guide therapy and to arrive at a prognosis.
Liver enzyme levels reveal little about organ integrity and are not useful for staging. But other parameters (specifically, bilirubin, albumin, and prothrombin time), combined with the presence (or absence) and severity of physical findings such as encephalopathy and ascites, are included in the Child-Pugh classification system ( TABLE 1 ),14 a widely used system that roughly indicates disease severity.15
The Model for End-stage Liver Disease (MELD)—and PELD, the pediatric model—use bilirubin, creatinine, and international normalized ratio values to classify disease severity. MELD and PELD scores are considered more accurate than the Child-Pugh score in determining short-term mortality,16 and are used by the United Network of Organ Sharing (UNOS) for liver allocation. You’ll find a calculator at http://optn.transplant.hrsa.gov/resources/MeldPeldCalculator.asp?index=97.17
Despite the progress in diagnostic techniques, the life expectancy and quality of life for patients with advanced cirrhosis remains poor. Patients routinely experience fatigue, pruritus, ascites, encephalopathy, and bleeding; dyspepsia and malnutrition are common, as well. Cirrhosis also carries the risk of life-threatening complications, partly due to comorbidities—most notably, osteoporosis, malabsorption, and rheumatic diseases. Liver transplantation has the potential to change the life expectancy of these patients, but because of the extensive waiting lists, candidates for transplant often die before a liver becomes available.
But for many patients who are in stable condition—those with compensated cirrhosis, that is—the prognosis is far more hopeful: In addition to providing standard medical care, including immunization, if necessary, and nutritional counseling, targeted therapy is crucial to slow, or stop, disease progression.