W. M. Melia

RISK FACTORS IN DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CIRRHOSIS: PROSPECTIVE STUDY OF 613 PATIENTS

In a prospective study of 613 patients with cirrhosis of different aetiological types increasing age, male sex, and non-UK nationality were found to be significant independent risk factors for the progression of cirrhosis to hepatocellular carcinoma. Seropositivity for hepatitis B surface antigen and the duration and aetiology of cirrhosis were not related to the development of the disease. Age and sex were also found to be significant risk factors when UK patients alone were considered. Seropositivity for hepatitis B surface antigen may be associated with hepatocellular carcinoma only because hepatitis B virus infection is a common cause of cirrhosis.

High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma.

Ten (9.3%) of 107 patients with hepatocellular carcinoma had considerably increased serum unsaturated vitamin B12 binding capacity. All 10 were young (mean 12 years), had no serum alpha-fetoprotein, and no underlying cirrhosis; all had a longer survival compared with patients without increased serum unsaturated vitamin B12 binding capacity in the study. Seven of the 10 patients had fibrolamellar hepatocellular carcinoma, a recently recognised histological variant, which was found in only one young patient without increased serum unsaturated vitamin B12 binding capacity and no alpha-fetoprotein among the remaining 97. This high degree of correlation between increased serum unsaturated vitamin B12 binding capacity and fibrolamellar hepatocellular carcinoma has not been reported before. Increased serum unsaturated vitamin B12 binding capacity may be of considerable help in diagnosis, prognosis, and monitoring treatment of this well-defined group of patients with hepatocellular carcinoma but no alpha-fetoprotein.

Induction of remission in hepatocellular carcinoma: A comparison of VP 16 with adriamycin

Following a pilot study of VP‐16.213 (180 mg/m2 on 3 consecutive days at 2 weekly intervals) in the treatment of patients with hepatocellular carcinoma, the efficacy of the drug was compared with that of adriamycin in another 35 patients in a randomized crossover trial. Each drug gave a similar response rate (18 and 28%, respectively) but the duration of response was significantly longer in those receiving Adriamycin. Some patients who had not responded to treatment with Adriamycin had worthwhile remission with VP 16.

Non-operative arterial embolisation in primary liver tumours.

Three patients with primary hepatic tumours were treated by selective arterial embolisation with gelatin-foam fragments to induce necrosis. In the two with histologically proved hepatocellular carcinoma ultrasonography suggested that necrosis had been induced, as did the rapid initial falls in serum alpha-fetoprotein concentration by 95 and 81% of the original values respectively. Treatment was continued with a course of adriamycin, and both patients remained well and symptom free at 10 and 12 months. In the third patient, who had an expanding and highly vascular benign hepatic adenoma associated with use of a contraceptive pill, embolisation obliterated the tumour mass. Tumour embolisation should be regarded as only the first step in managing hepatocellular carcinoma and as a means of reducing appreciably the viable tumour mass before chemotherapy. It may be used as the primary and definitive treatment in patients with benign liver tumours.

B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis.

Oral metoprolol, in a dose sufficient to reduce resting pulse rate by 25%, was compared with repeated injection sclerotherapy for the long term management of variceal bleeding. The prospective, randomised study was undertaken in 32 patients with biopsy proven cirrhosis and variceal bleeding who were Grade A or B on a modified Childs classification. In the 15 patients receiving metoprolol, portal pressure showed a mean fall of 3.7 mmHg (17.3 +/- 1.2 to 13.6 +/- 1.2 mmHg, p less than 0.01) after four weeks of continuous therapy, as compared with pretreatment levels. Nine of the 15 patients taking metoprolol had further bleeding (total of 21 episodes) compared with six of 17 in the sclerotherapy group (nine episodes). The risk of bleeding per patient/month of follow up was three times higher in the metoprolol group compared with those treated by sclerotherapy (0.14 and 0.04 respectively, p less than 0.025). Rebleeding in the metoprolol group occurred in six of the patients who had a fall in portal pressure of 10% or more.

Serum ferritin in hepatocellular carcinoma. A comparison with alphafetoprotein

The serum ferritin level was raised in 34 of 35 (97%) patients with hepatocellular carcinoma and in 20 of 23 (87%) with uncomplicated cirrhosis. Levels rose following therapeutic embolisation in 14 of 15 patients and continued to rise in 85% of all tumor patients who showed no clinical response to chemotherapy (intravenous Adriamycin) whereas in those who did respond the serum ferritin level fell. By contrast, there was a fall in serum alphafetoprotein immediately after embolisation but like serum ferritin, alphafetoprotein levels rose with disease progression and only fell in those achieving clinical remission. Serum ferritin has no role in the differential diagnosis of hepatocellular carcinoma but may be a useful marker in monitoring response to chemotherapy particularly in the alphafetoprotein‐negative patient.

Plasma carcinoembryonic antigen in the diagnosis and management of patients with hepatocellular carcinoma

The value of serial carcinoembryonic antigen (CEA) measurements as a marker of disease progression or in monitoring treatment was investigated in patients with hepatocellular carcinoma. Of 40 patients, including 16 with normal serum alpha‐fetoprotein (AFP) concentrations, 29 (72.5%) had abnormal plasma CEA at presentation. Although this was more common in patients with pre‐existing cirrhosis, the mean and range of plasma CEA were similar in patients with and without pre‐existing hepatic disease. There was no correlation between plasma CEA and any biochemical parameter of hepatic function, although plasma CEA concentrations were significantly lower in patients with well‐differentiated tumors. CEA concentrations increased in 71% of patients who had no response to cytotoxic drugs, but CEA also increased in 62.5% of those patients who did respond. Plasma CEA concentrations were elevated in 62.5% of patients with normal and 79% of patients with raised serum AFP on admission to the hospital. There was no correlation between individual AFP and CEA concentrations. Although elevated plasma CEA levels may be of diagnostic value in patients with hepatocellular carcinoma in the absence of pre‐existing hepatic disease, and in those with normal serum AFP, our findings indicate that it does not behave as a true tumor marker.