| |
Clinical Course of Chronic Hepatitis C in Patients with Very High Serum alpha-Fetoprotein Levels and Normal Hepatic Imaging
|
| |
| |
The American Journal of Gastroenterology
April 2005
Stevan A. Gonzalez, M.D.
Ira M. Jacobson, M.D.
Division of Gastroenterology and Hepatology
Center for the Study of Hepatitis C
Weill Medical College of Cornell University
New York, New York
LETTER TO THE EDITOR: Periodic serum alpha-fetoprotein (AFP) levels and hepatic imaging are widely used in screening for hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) and cirrhosis (1), yet the clinical significance of elevated AFP in CHC patients without a diagnosis of HCC is uncertain. We read with interest the article by Hu et al. (2), in which this population was studied. Hu et al. found that elevated AFP levels in this setting were associated with advanced fibrosis, elevated aspartate aminotransferase, and prolonged prothrombin time. However, these patients were not followed over the long-term to evaluate the potential risk of HCC. Although studies have reported high specificities for elevated AFP levels in screening for HCC (1), no guidelines exist for the management of CHC patients who have very high serum AFP and normal hepatic imaging.
We performed a cross-sectional retrospective analysis of 16 CHC mono-infected patients who were evaluated at an outpatient academic hepatology practice and were identified as having serum AFP levels >100 ng/ml and normal hepatic imaging using abdominal ultrasound with CT or MRI, or all three. Initial imaging studies were obtained within a mean of 2.4 months (range 1-8 months) of AFP values >100 ng/ml. We then evaluated subsequent trends in AFP levels, clinical and demographic features, and incidence of HCC. Eight patients (50%) developed overt HCC during a mean follow-up of 4.6 yr (range 1.4-10.9 yr). All 16 patients had either biopsy-proven (n = 7) or clinical and radiographic evidence of cirrhosis (n = 9).
Two short-term trends in AFP emerged using three subsequent AFP levels obtained at least 1 month apart: persistently >100 ng/ml (n = 10) and decreasing to <40 ng/ml (n = 6). No patient with a decreasing trend to <40 ng/ml developed HCC. Of 11 patients who initially presented for outpatient evaluation with AFP levels >100 ng/ml, 5 (45%) developed HCC, all of whom had persistently elevated AFP at the third time point in contrast with HCC-negative patients (mean AFP ± standard error, 145.9 ± 23.9 vs 68.2 ± 12.9, respectively, p= 0.05) (Fig. 1). The other five patients selected for our study did not develop AFP levels >100 ng/ml until after they had already been followed as outpatients over a mean of 3.4 yr (range 15 months to 7 yr).
Another subgroup of 11 patients were followed to at least 5 yr after the initial AFP >100 ng/ml. In these patients, mean yearly AFP increased in patients who developed HCC (n = 4), while AFP in HCC-negative patients (n = 7) decreased (Fig. 2, p= 0.001). The other five patients were followed for a mean of 1.2 yr (range 4 months to 2 yr), four of whom developed HCC and one patient was lost to follow-up. All four of these patients who developed HCC had an increasing trend in mean yearly AFP levels. Age, gender, race, alcohol or smoking history, HCV RNA, HCV genotype, mean ALT, and whether patients had received interferon-based therapy did not differ between patients who did and did not develop HCC (Table 1).
No patients in our study who developed HCC demonstrated a decreasing short-term trend in serial AFP levels. Additionally, mean AFP increased over a 5-yr follow-up in patients who developed HCC. All patients in our study had either biopsy-proven or clinical and radiographic evidence of cirrhosis, therefore these findings may not necessarily apply to CHC patients without cirrhosis. Patients with very high AFP levels and normal hepatic imaging who are characterized by a trend of persistently elevated or increasing AFP should be followed very closely and frequent imaging should be obtained.
Stevan A. Gonzalez, M.D.
Ira M. Jacobson, M.D.
REFERENCES
1. Gebo KA, Chander G, Jenckes MW, et al. Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review. Hepatology 2002;36: S84-92.
CrossRef Abstract MEDLINE Abstract ISI Abstract
2. Hu K, Kyulo NL, Lim N, et al. Clinical significance of elevated alpha-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol 2004;99: 860-5.
Synergy Abstract MEDLINE Abstract ISI Abstract
|
|
| |
| |
|
|
|
