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To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.

As part of a larger study designed to investigate the interaction of factors such as cirrhosis and hepatitis B virus infection as aetiological agents in the development of hepatocellular carcinoma, we investigated the status of hepatic HBV-DNA sequences in 156 cirrhotic patients. Forty-one were HBsAg seropositive and 18 (44%) of these had HBV-DNA sequences detectable in their livers. There are also 26 subjects who showed markers of a previous HBV infection (anti-HBs/anti-HBc), only one (4%) of whom had demonstrable hepatic HBV-DNA sequences. No sequences were found in any of the remaining 89 patients who were seronegative for all markers. Thus, liver HBV-DNA was only detected in the presence of a serum marker, usually HBsAg.

To determine whether previous observations suggesting reduced ability of thyroxine-binding globulin (TBG) to bind exogenous thyroid hormones in hepatocellular carcinoma (HCC) might form the basis of a useful clinical test, we have investigated a larger series involving 49 patients and 10 healthy subjects. The binding ratio (mol hormone bound/mol TBG at a given hormone concentration) for both T4 and T3 was significantly reduced when compared to both cirrhotic and normal subjects. No overlap in T4 binding occurred between HCC patients and the control groups. Serial measurements on serum samples obtained from five cirrhotic patients who ultimately developed HCC revealed significant reductions in binding for both hormones up to 60 months prior to the clinical diagnosis of HCC. A reduced ability to bind thyroid hormones appears to be a specific feature of serum TBG from HCC patients and is one of the earliest alterations seen among cirrhotic subjects who ultimately develop the disease.

The titre of HBsAg in the serum of patients with HBsAg seropositive hepatocellular carcinoma rose in 12 (80%) of 15 cases during chemotherapy with either adriamycin or etoposide and in five cases there was at least a four-fold rise in titre. Anti-HBs and anti-HBc status did not change and serum markers of HBV infection did not become apparent in the 32 patients who were seronegative at presentation. The chemotherapy-related rise in HBsAg titre did not appear to be responsible for deterioration in hepatocellular function and it was not associated with any change in HBeAg/anti-HBe status.