A 69-year old man was admitted to our hospital in October 2003 for examination of two liver tumors. He had been diagnosed with hepatitis B in 1994 and treated with glycyrrhizin. His liver function deteriorated gradually, with ascites appearing in May 2001. He was first admitted to our hospital for treatment of intractable ascites (Figure ). Laboratory tests showed that his serum albumin (alb) concentration was 2.7 g/dL, his total bilirubin (T-Bil) was 2.8 mg/dL, his aspartate aminotransferase (AST) was 54 IU/L, his alanine aminotransferase (ALT) was 43 IU/L, and his prothrombin time (PT) was 42%. Administration of diuretic drugs was not effective, but treatment with a preparation of albumin resulted in the disappearance of ascites 1 mo later. Afterward, the ascites was kept under control by administration of diuretics. In October 2003, a computed tomographic (CT) scan of the abdomen revealed two HCCs (4.5 and 2.5 cm in diameter) in the right hepatic lobe (Figure , ). Laboratory tests showed alb 2.5 g/dL, T-Bil 2.4 mg/dL, AST 152 IU/L, ALT 98 IU/L, PT 47%, indocyanine green at 15 min after injection (ICGR15) 48%, alpha-fetoprotein 444 ng/mL, and protein induced by vitamine K absence or antagonist II <10 mAU/mL. He was positive for HBe antigen, negative for HBe antibody, and had an HBV-DNA viral load of 6.7 log copies/mL. Beginning in November 2003, he was treated with 100 mg/d lamivudine. The two HCCs were treated by transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (Figure , ). Both tumors were treated successfully and the patient’s liver function recovered gradually after initiation of lamivudine treatment. In September 2005, an abdominal CT scan revealed a recurrent HCC, located near one of the previously treated tumors; this lesion was treated successfully with TACE and RFA. At this time, laboratory tests showed alb 3.7 g/dL, T-Bil 0.7 mg/dL, AST 23 IU/L, ALT 22 IU/L, PT 84% and ICGR15 22%. All HCC treatments were based on clinical practice guidelines in Japan[5
], with the patient providing informed consent.
Figure 1 Computed tomography in our patient. It shows a cirrhotic pattern of the liver and massive ascites at first admission (A); Dynamic computed tomography revealed two hepatocellular carcinomas, 4.5 cm (B) and 2.5 cm (C) in diameter, in the right lobe; These (more ...)
In May 2006, two HCC recurrences were detected in the right liver lobe and treated with TACE and RFA. Laboratory tests showed good liver function, alb 3.9 g/dL, T-Bil 1.1 mg/dL, AST 22 IU/L, ALT 11 IU/L, PT 95% and ICGR15 25%. In June 2007, a recurrent HCC was treated with TACE and RFA. Liver function was also excellent at this time (alb 4.0 g/dL, T-Bil 0.7 mg/dL and PT 100%). In September 2007, his viral load had again increased, with breakthrough hepatitis, and the YMDD mutation was detected. Treatment with adefovir dipivoxil plus lamivudine resulted in a gradual reduction in viral load. In December 2007, abdominal CT revealed five HCCs in the right lobe; these were treated by TACE and RFA. The patient was then treated with low-dose cisplatin and 5-fluorouracil infused through the hepatic artery. Laboratory tests showed alb 4.1 g/dL, T-Bil 1.0 mg/dL, AST 38 IU/L, ALT 30 IU/L, PT 88% and ICGR15 5%. Due to the development of a pseudoaneurysm in his hepatic artery, infusion of chemotherapy was discontinued. In March 2009, two HCCs were detected in the right lobe and were treated by RFA. Laboratory tests showed alb 3.7 g/dL, T-Bil 0.7 mg/dL, AST 35 IU/L, ALT 31 IU/L, PT 77% and ICGR15 10%. In April 2009, abdominal CT and CT angiography revealed a tumor thrombus in the right portal vein, but no lesion could be detected in the left lobe (Figure ). Although he was diagnosed with decompensated cirrhosis, of Child-Pugh C, when first hospitalized, lamivudine treatment improved his liver function sufficiently, with an improvement of ICGR15 results to < 10%, to allow the successful performance of a right hepatectomy in April 2009 (Figure ). After liver resection, his AST rose to 1220 IU/L, his T-Bil to 1.9 mg/dL, and his PT decreased to 54%, followed by gradual recovery of liver function. He recovered well and left the hospital 1 mo after surgery.
Computed tomography during hepatic arteriography, showing a portal tumor thrombus (arrow) in the right portal vein. Hepatocellular carcinoma was not detected in the left lobe.
Figure 3 Macroscopic and microscopic appearance of the resected liver. A: A tumor thrombus was detected in the right portal vein (arrow); B: A moderately differentiated hepatocellular carcinoma with a trabecular pattern was seen in the right portal vein [hematoxylin (more ...)
Histologic examination of the extracted specimen showed a moderately differentiated HCC with portal tumor thrombus (Figure ) and multiple intrahepatic metastases. Fibrosis of varying extent was observed in the cancer-free area, with some areas showing severe fibrosis with pseudolobules and others showing mild fibrosis (Figure ). Abdominal CT in June 2009 suggested the recurrence of HCC in the left lobe (Figure ), and abdominal angiography revealed multiple HCCs. These tumors were treated by TACE, but this was not effective. The left lobe tumors subsequently enlarged and the patient’s liver function deteriorated gradually. The patient died in December 2009 (Clinical course Figure ).
Abdominal computed tomography showing the recurrence of hepatocellular carcinoma (arrow) in the left lobe two months after right hepatectomy.
Figure 5 Clinical course of the patient. After lamivudine administration, his liver function gradually improved despite repeated treatments for hepatocellular carcinoma (HCC), and his indocyanine green at 15 min after injection (ICGR15) test score was 5% 4 years (more ...)