Indicators pointing to cholestasis? It’s time for ultrasonography
While biopsy is considered the gold standard for diagnosing and staging chronic cholestatic liver disease and can exclude an extrahepatic obstruction, it should be employed only if blood tests have been confirmed, second-level tests have been performed, and ultrasound is inconclusive.12 (More on biopsy in a bit.)
Ultrasonography is a low-cost, widely available, noninvasive test that allows easy identification of extrahepatic dilatation of the biliary tree and sometimes the underlying cause, as well. Ultrasonography identifies extrahepatic cholestasis by allowing visualization of an enlarged choledochus (>7 mm) or common hepatic duct (>5 mm) and an intrahepatic bile duct diameter that is more than 40% larger than adjacent branches of the portal vein.13 However, ultrasonography has a low diagnostic sensitivity for many conditions (eg, 15% to 89% for detecting common bile duct stones),14 requiring other diagnostic procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), before reaching a diagnosis.
For asymptomatic patients with cirrhosis or those at an early stage of liver disease, ultrasound at 6-month intervals combined with serum liver function tests can be useful to track disease progression and screen for hepatocellular carcinoma or cholangiocarcinoma.15,16
New noninvasive methods. Noninvasive tools for evaluating the presence and severity of liver fibrosis and for differentiating cirrhosis from noncirrhotic conditions have positive predictive values >85% to 90% for some chronic liver diseases.17 Transient elastography, which assesses liver stiffness, is one such method. Although it is often used successfully, morbid obesity, small intercostal spaces, and ascites limit its diagnostic capability.18 Recently, some questions about the validity of elastography to assess the extent of fibrosis in patients with chronic cholestatic conditions have been reported.19,20
Suspect intrahepatic cholestasis? Your next steps
If imaging techniques do not show bile duct obstruction and you suspect the intrahepatic form, second-level tests could have strategic importance. This is where antimitochondrial antibodies (AMAs) come in. AMAs are immunoglobulins (IgG and IgM) directed against mitochondrial antigens. They are important markers for PBC, which is a T-lymphocyte-mediated attack on small intralobular bile ducts resulting in their gradual destruction and eventual disappearance. The sustained loss of intralobular bile ducts leads to signs and symptoms of cholestasis and eventually results in cirrhosis and liver failure.
AMA serum levels show high sensitivity and specificity (90% and 95%, respectively) for PBC.21 Some PBC patients (<5%) show histologic confirmation of the disease, but have negative AMA tests (AMA negative PBC or autoimmune cholangitis).22 Therefore, according to the American Association for the Study of Liver Diseases, diagnosis of PBC is guided by the combination of serologic, biochemical, and histologic criteria.23 Many PBC patients with or without a positive AMA (≥1:40) also have positive circulating antinuclear antibodies (ANA; ≥1:80). The recent availability of lab tests for antibodies (anti-M2, anti-gp120, anti-sp100) has allowed identification of subgroups of patients who have a more aggressive form of PBC. Patients with PBC often have elevated levels of circulating IgM (>280 mg/dL).
Continue to: Other circulating antibodies