Functional hepatic imaging and disease recurrence after liver transplantation

Cirrhosis and its disease-related complications are the 12th leading cause of overall mortality and the second leading cause of gastrointestinal death in the United States. The major disease-related complications from cirrhosis are related to portal hypertension (esophageal variceal hemorrhage, ascites, hepatic encephalopathy) and hepatocellular carcinoma. For the majority of affected patients, these clinical outcomes are directly related to the development of progressive hepatic fibrosis. Despite advances in the medical management of cirrhosis, there remains an opportunity to improve the detection rate of individuals with progressive fibrosis who might benefit from early intervention. To date, liver biopsy has been the gold standard for detecting hepatic fibrosis. The majority of classification systems recognize 5 stages of fibrosis, graded as F0 (no fibrosis), F1 (portal fibrosis), F2 (periportal fibrosis), F3 (bridging fibrosis), and F4 (cirrhosis). Clinically significant fibrosis is generally defined by F2 involvement or greater. However, a number of studies have demonstrated excessive rates of sampling error (25%-40%) resulting in poor reproducibility. In addition, the extent of variation from observer interpretation by expert histopathologists may be as high as 20%. Given these limitations, a growing number of investigations have focused on validating noninvasive methods for detecting hepatic fibrosis. A number of serum markers representing the process of hepatic fibrosis have been studied to date. Unfortunately, the majority of these studies are limited by retrospective study designs, low rates of liver biopsy reproducibility, and the inclusion of patients with a narrow spectrum of disease severity. Advances in cross-sectional imaging that focus on detecting static morphologic alterations of liver disease can be used to identify cases of established cirrhosis. However, the ability to detect early and intermediate stages of fibrosis with these techniques remains limited. The palpation and detection of tissue stiffness by physical examination has traditionally been associated with organic disease processes, including malignancy. The development of techniques to “palpate” solid-organ tissue by imaging has recently been identified. Regional imaging through wave propagation techniques has the potential to assess the mechanical properties of human tissue in health and disease. Measuring the velocity of wave propagation can be used to calculate “stiffness,” which may be highly associated with known endpoints of injury such as fibrosis. Recent work has focused on the technique of ultrasound-based elastography to predict the severity of hepatic fibrosis based on measurements of liver stiffness. To date, it appears that a correlation exists between mean liver stiffness (measured in kilopascals) and stage of fibrosis in patients undergoing liver biopsy. Similar findings are observed in patients with varying degrees of cirrhosis, as higher stiffness values correspond to the development of disease-related complications. In the current issue of Liver Transplantation, Carrion et al. examined the role of ultrasound-based transient elastography to detect advanced hepatic fibrosis in patients with recurrent hepatitis C infection after liver transplantation. In addition, the performance of hepatic venous pressure gradient (HVPG) measurement was done to assess the degree of portal hypertension in this cohort. From a total of 124 patients, the sensitivity