A 59-year-old male with confirmed hepatitis C-related liver cirrhosis of over 10 years duration was admitted to our hospital in March 2003 for an evaluation of his functional and histopathologic status of the liver, and his levels of aminotransferases and alpha-Fetoprotein (AFP) that were checked at the outpatient department had persistently risen. At the time of the admission, he presented with general weakness and loss of appetite, and the vital signs were normal. The initial serology revealed mild hyperbilirubinemia with a total bilirubin of 1.3 mg/dL. The aminotransferase levels were 116 IU/L and 33 IU/L for aspartate (AST) and alanine (ALT) aminotransferase, respectively, with an alkaline phosphatase (ALP) 233 IU/L and γ-glutamyl transpeptidase (GGT) 109 IU/L. The AFP level checked on the admission was 4,720 ng/mL. The HBsAg and anti-HBs tests were negative and nonreactive. The anti-HCV (IgG) was reactive with a titer of 181.14 S/CO and the HCV (PCR) was 4+. A quantitative measurement of HCV-RNA was not carried out. The other serologic findings were normal. He was a type II diabetic and had no history of variceal bleeding, ascites, encephalopathy or any intake of herbs or alcohol before the admission. He had been followed up at the Department of Gastroenterology of the hospital since May 2002, and the aminotransferase levels checked since then were shown to be gradually increasing, and the AFP levels had increased markedly at the time of her admission (Table 1). As shown in the Table 1, the aminotransferases (AST/ALT) and AFP levels had increased from 57/18 IU/L and 18.1 ng/mL, respectively, in May 2002 to 196/71 IU/L and 4,720 ng/mL, respectively, in February 2003 until the commencement of antiviral therapy. Computed tomography (CT) of the liver taken during the admission showed no definite mass or intrahepatic focal lesion in the liver (Figure 1A). There were no other clinically significant abnormalities found on the CT scan. Hepatic angiography was carried out for the markedly elevated AFP level to rule out any possibility of hepatocellular carcinoma, but no definite tumor staining was noted in liver parenchyme (Figure 2). The sequentially performed liver biopsy showed severe porto-periportal inflammatory activity, mild lobular inflammatory activity and septal fibrosis, and these findings were compatible with chronic active hepatitis in liver cirrhosis (Figure 3). The post-lipiodol hepatic CT scan taken 2 weeks after the angiography for detecting any hidden tumor also showed no focal lesion or remnant of lipiodol staining in the liver (Figure 1B).

The patient was treated with antiviral therapy of Interferon (IFN) 3 million units three times a week along with Ribavirin 500 mg twice a day, and then the patient was discharged. The aminotransferases (AST/ALT) and AFP levels taken on follow up at the outpatient department after discharge decreased to 89/90 IU/L and 40.6 ng/mL, respectively, over a period of 3 months. He has taken the anti-viral therapy (IFN and Ribavirin) for over 6 months, and the aminotransferase levels have not changed significantly, and the AFP level did not increase any further. Moreover, the HCV (PCR) that was checked at the end of the antiviral therapy had converted to 'negative'. During the course of the therapy, follow-up imaging studies, abdominal ultrasonography and liver CT scan were undertaken along with serologic evaluation, and yet no evidence of tumor in the liver parenchyme was discovered.

A 58-year-old female with confirmed hepatitis B-related liver cirrhosis was hospitalized for a detailed evaluation on the hepatic status in February 2003 because the AFP level checked at the outpatient department had tenaciously risen. From March 2002 to February 2003, the aminotransferases levels were slightly elevated, but the AFP level has increased from 8.55 ng/mL in March 2002 to 5,480 ng/mL in February 2003 (Table 2). At the time of the admission, she presented with no specific complaint. The physical examination showed no abnormalities except mild icteric sclerae. She had no past history of variceal bleeding, ascites, encephalopathy or intake of herbs or alcohol before her admission. The initial serology revealed macrocytic hyperchromic anemia (Hb 11.1 g/dL, Hct 27%) and thrombocytopenia (29,000 mm³), moderate hypoalbuminemia (2.7 mg/dL), mild hyperbilirubinemia (total bilirubin 2.3 mg/dL) and elevated aminotransferase levels (AST/ALT 130/42 IU/L). The AFP level checked on the admission was 5,480 ng/mL. The laboratory study on viral markers showed reactive HBsAg/nonreactive Anti-HBs, reactive HBeAg and an HBV-bDNA level of 5,582 pg/mL. A quantitative measurement of HbeAg was not carried out, and the other serologic findings were normal. A liver CT scan carried out during the admission confirmed liver cirrhosis with splenomegaly, ascites and portal hypertension, but there was no mass or focal lesion found in the liver (Figure 4A). There was no definite tumor staining on both lobes of the liver on the hepatic angiography (Figure 5). A liver biopsy could not be carried out on account of the patient's adamant refusal. A post-lipiodol hepatic CT scan was subsequently undertaken 2 weeks after the angiography for detecting any hidden tumor, and it showed neither focal lesion nor lipiodol staining in the liver (Figure 4B). Since the initiation of antiviral therapy with Lamivudine 100 mg once a day, the aminotransferases (AST/ALT) and AFP levels have decreased approximately to 35/19 IU/L and 28.6 ng/mL, respectively, over a period of 3 months. The patient is currently still on the medication as the HBV (PCR) remains positive, but the aminotransferase levels are normal and the AFP level has fallen to 5.37 ng/mL after 9 months of therapy.