The blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities. The portal blood supply was evaluated with computed tomography (CT) during arterial portography (CTAP); the arterial blood supply was evaluated with hepatic angiography, CT angiography, CT following intraarterial injection of iodized oil, or ultrasound following intraarterial injection of carbon dioxide microbubbles. A total of 84 surgically confirmed hepatocellular carcinomas (HCCs) (less than or equal to 3 cm) and 25 areas of adenomatous hyperplasia (AH) were included in the study. At CTAP, a portal blood supply was seen in 96% of cases of AH and only 6% of HCCs (chi 2, P less than .005). In contrast, an arterial supply greater than that of the surrounding liver was verified in 94% of the HCCs and only 4% of the cases of AH (chi 2, P less than .005). The blood supply of areas of AH with atypical hepatocytes and the blood supply of well-differentiated HCCs (Edmondson grade 1) tended to be intermediate between that of AH without atypia and that of HCC that was Edmondson and Steiner grade 2 or greater. Evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early-stage HCC.

The effectiveness of subsegmental transcatheter arterial embolization (TAE) therapy for small hepatocellular carcinomas (HCCs) was retrospectively analyzed. TAE was performed in 100 patients with liver cirrhosis. There was a total of 124 nodular-type HCCs less than 4 cm in diameter. TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by gelatin sponge particles or a mixture of iodized oil and absolute ethanol into the more distal branches of the subsegmental artery. Complete necrosis was seen at histologic examination in seven of 11 resected lesions. Among the remaining 113 lesions in 90 patients followed up without surgery, the 1-and 4-year local recurrence rates after TAE were 18% and 33%, respectively. The 1- and 4-year survival rates for 82 patients with Child class A or B disease were 100% and 67%, respectively. No substantial deterioration of liver function was observed. Subsegmental TAE improved the prognosis of the patients with liver cirrhosis associated with small HCCs.

We compared the sensitivity of the polymerase chain-reaction (PCR) assay to that of slot-blot hybridization for detecting hepatitis B virus (HBV) DNA in the serum of 31 patients with chronic hepatitis. Of 14 chronic hepatitis patients positive for both HBV surface and HBV e antigens, 9 were positive for HBV DNA by slot-blot hybridization and all 14 by PCR. Also, of 9 patients positive for HBV surface antigen and antibody against HBV e antigen, 2 were positive for HBV DNA by slot-blot analysis and 8 by PCR. Finally, in 8 patients positive for antibody against HBV surface antigen, none were positive for HBV DNA by slot-blot hybridization, but 4 were positive by PCR. We find that analysis by the PCR technique provides a >104-fold increase in sensitivity over the slot-blot hybridization assay. This result represents an important breakthrough in sensitivity because it is now possible to detect as few as three HBV DNA genomes per sample of serum.The polymerase chain reaction (PCR) technique is a method for amplifying nucleic acid by repeated cycles of hightemperature template denaturation, oligonucleotide primer hybridization, and polymerase extension. The thermostable polymerase of Thermus aquaticus (Taq) is often used because it can withstand the high denaturation temperatures without loss of enzymatic activity. Previous investigations with this technique have shown amplification of >105-fold over the input quantity of nucleic acid (1, 2). We have used PCR amplification, combined with agarose gel electrophoresis and Southern blot hybridization analysis, to detect extremely small quantities of hepatitis B virus (HBV) DNA in the serum of chronic hepatitis patients.

We examined the quasispecies of the hepatitis C virus genome in 28 patients with liver disease of varying severity. Nucleotide sequences of the hepatitis C virus genome spanning the region from the core to envelope were used to calculate the nucleotide diversity: 0.58% +/- 0.88% in 5 patients with acute hepatitis, 0.85% +/- 0.62% in 5 patients with chronic persistent hepatitis, 1.79% +/- 0.92% in 11 patients with chronic active hepatitis, 3.05% +/- 1.26% in 4 patients with cirrhosis and 2.71% +/- 1.47% in 3 patients with cirrhosis complicated by hepatocellular carcinoma. Thus the intrapatient variation in nucleotides increased significantly with severity of liver disease (p < 0.01), except in those cases of cirrhosis complicated by hepatocellular carcinoma. Multivariate analysis including the histology, duration of infection, age, sex, history of blood transfusion and serum level of ALT at diagnosis as variables showed that the histological finding was the strongest independent factor of the nucleotide diversity (p = 0.003). Serial analysis of the genome in three patients demonstrated that the intra-patient variation in nucleotides increased with the progression of liver disease. The magnitude of the intrapatient variation in nucleotides deduced from the observed changes in the patients was correlated with the mean serum levels of ALT. These findings suggest that the degree of diversity of HCV quasispecies is related to the progression of liver disease.

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