1. The growth characteristics of a human hepatocellular carcinoma, derived from the PLC/PRF/5 cell-line ('Alexander'), transplanted into sub-lethally irradiated athymic (nu/nu) mice have been examined. The xenograft re-expresses alpha-foetoprotein production although this tumour marker was not detected during cell culture in vitro. 2. There is a positive correlation between serum alpha-foetoprotein concentration and tumour mass (r = 0.978), validating the use of this tumour marker to assess growth. 3. In mice with progressively growing xenografts there is a linear correlation between log serum alpha-foetoprotein concentration and time, compatible with exponential tumour growth. Growth of the human hepatocellular carcinoma xenograft is rapid, with an alpha-foetoprotein doubling time of 6.1 +/- 2.1 days (+/- standard deviation) and a mass doubling time of 3.6 +/- 1.2 days (+/- standard deviation). 4. The tumour cell birth or production rate, determined by a stathmokinetic (metaphase arrest) technique using vincristine, is 15.7 +/- 3.8 (95% confidence limits) cells per 1000 cells per hour. The tumour cell loss factor (49%) is low and may contribute to the rapid growth of this human hepatocellular carcinoma xenograft.

Animals↗

PubMed1983

Acyclovir in hepatitis B antigen-positive chronic liver disease: inhibition of viral replication and transient renal impairment with iv bolus administration.

Six patients with hepatitis B virus (HBV) related chronic liver disease were treated with acyclovir, 5-15 mg/kg 8 hourly, given as an iv bolus or iv infusion over 1 h for up to 7 days. Two patients treated with 10 and 15 mg/kg 8 hourly showed a decrease in HBV-DNA polymerase and HBV-DNA when mean trough acyclovir plasma concentrations of 5.0 +/- 0.6 and 13.2 +/- 3.0 microM were attained. Inhibition of viral replication was not seen in patients treated with lower doses. Transient renal impairment was seen in two patients who received high dosage by the iv bolus mode of administration. This complication may be prevented by a high oral fluid intake or iv infusion of the drug over 1 h. Further study with acyclovir 15 mg/kg 8-hourly given as an iv infusion for longer periods is warranted.

Acyclovir↗

PubMed1983

Nuclear magnetic resonance (NMR) imaging in Wilson disease.

Nuclear magnetic resonance (NMR) scans of the head and liver were obtained in 13 patients with Wilson disease, and the results were compared with computed tomography (CT). Twelve age and sex matched normal controls were also scanned with NMR. The subjects were scanned using repeated free induction decay (RFID), inversion-recovery (IR), and spin-echo (SE) sequences. The IR scans of the brain provided excellent anatomical localisation while SE scans highlighted pathological areas. Within the brain, NMR demonstrated abnormalities in two patients with normal CT scans. More extensive involvement was shown with NMR in three additional cases. In the liver, NMR and CT showed similar abnormalities of morphology. T1 values were within the normal range in all cases, including three patients with high liver copper levels at the time of NMR examination.

Adolescent↗

PubMed1983

The effect of ranitidine on the plasma clearance and hepatic extraction of indocyanine green in patients with chronic liver disease.

Since hepatic clearance of ICG is reduced by H2-receptor antagonists in normal subjects, it has been suggested that they reduce liver blood flow. We have studied the effect of intravenous ranitidine on ICG clearance in twelve patients with chronic liver disease. Wedged and free hepatic venous pressure were measured before and after intravenous ranitidine in nine of the patients, and the hepatic extraction of ICG was determined in six patients. ICG clearance fell by 22 +/- 11% (s.e. mean) 60 min after ranitidine. In patients in whom ICG clearance fell after intravenous ranitidine the hepatic extraction of ICG was also reduced. There was no significant change in the gradient between wedged and free hepatic venous pressure after ranitidine. It is therefore unlikely that ranitidine lowers liver blood flow.

Adolescent↗

PubMed1983

Incidence of hepatitis B virus infection in alcoholic liver disease, HBsAg negative chronic active liver disease and primary liver cell cancer in Britain.

A study has been undertaken to determine the incidence of serum markers of hepatitis B virus (HBV) infection in British caucasian patients with biopsy-proven alcoholic liver disease (n = 56), HBsAg negative chronic active liver disease (CALD) (n = 47) and primary liver cell cancer (PLCC) (n = 27), compared to a hospital control population without liver disease (n = 112). No increased incidence of any serum marker of HBV infection was found in alcoholic liver disease or in 'lupoid' CALD (antinuclear factor positive 1:40 and/or smooth muscle antibody positive greater than 1:40). In contrast, the incidence of antibody to HB surface and core antigens was significantly increased (p less than 0.05) in patients with cryptogenic CALD. The incidence of hepatitis B surface antigen and antibodies to HB core and 'e' antigens was significantly increased (p less than 0.005) in PLCC.

Female↗

PubMed1983

Randomised, controlled study of transhepatic obliteration of varices and oesophageal stapling transection in uncontrolled variceal haemorrhage.

Percutaneous transhepatic obliteration and surgical stapling transection of the oesophagus with the EEA gun were compared prospectively in the treatment of uncontrolled oesophageal variceal haemorrhage unresponsive to conservative measures. Twenty patients with cirrhosis, with a patient portal vein and who were considered suitable for general anaesthesia and surgery, were randomised to two treatment groups (10 patients each). Immediate arrest of haemorrhage was achieved in 17 patients (nine surgery, eight obliteration). In one other patient, stapling transection succeeded where attempted transhepatic obliteration failed, and in another patient obliteration succeeded where attempted transection had failed. One patient continued to bleed and died following attempts at both procedures. Two other patients also died in hospital, without rebleeding following surgery. Variceal rebleeding during the same hospital admission occurred in two patients in the obliteration group and in none after surgery. Oesophageal stapling transection compares very favourably with a non-surgical technique such as transhepatic obliteration of varices in the emergency treatment of uncontrolled variceal haemorrhage in patients with moderate liver failure.

Adult↗

PubMed1983

The biliary excretion and pharmacokinetics of mezlocillin in jaundiced patients with external bile drainage.

The biliary excretion and pharmacokinetics of mezlocillin have been studied in jaundiced patients with total external bile drainage through a percutaneous transhepatic catheter. In 10 of 11 studies, 2 g mezlocillin intravenously resulted in biliary concentrations sufficient to exceed the minimum inhibitory concentrations of most common biliary pathogenic organisms. In 6 h, 0.2-6.2% of the dose given was recovered in bile. The biliary clearance was 0.21-7.82 ml/min and increased with the duration of biliary decompression. The serum half-life of mezlocillin was prolonged (1.81 +/- 0.23 h, mean +/- SD), and was due to reduced biliary and renal clearance.

Adolescent↗

PubMed1983

Association of primary sclerosing cholangitis with HLA-B8.

The frequency of HLA antigens was studied in 25 patients with primary sclerosing cholangitis and compared with a control group of 562 kidney donors. Fourteen patients also had ulcerative colitis. A significant increase in the frequency of HLA-B8 (60%) was found in the primary sclerosing cholangitis patients compared with controls (25%) (p less than 0.001). HLA-B8 was found in eight patients with ulcerative colitis. The frequency of HLA-B12 was significantly decreased (8%) compared with controls (30%) (p less than 0.02). Piecemeal necrosis was observed on liver histology in 66% of HLA-B8 positive and 50% of HLA-B8 negative patients. Low titres of serum autoantibodies were frequently found in the primary sclerosing cholangitis group but did not correspond to the presence of HLA-B8. Raised serum concentrations of IgM and IgG were not related to HLA-B8. This study has shown that in patients with primary sclerosing cholangitis there exists a disease susceptibility gene closely associated with the B locus of the major histocompatibility complex which may be modified by other factors such as ulcerative colitis. Patients with ulcerative colitis and HLA-B8 may be particularly liable to develop primary sclerosing cholangitis.

Autoantibodies↗

PubMed1983

Copper chelation therapy in intrahepatic cholestasis of childhood.

The effect of copper chelation was studied in a group of children with intrahepatic cholestasis of childhood (IHCC) and increased liver copper levels. Initial therapy was D-penicillamine (10 mg/kg/day), being replaced by triethylenetetramine dihydrochloride (20 mg/kg/day) when side-effects of D-penicillamine occurred. Eight children completed two years of copper chelation. Pruritus remained the main symptom and did not improve. Two patients developed D-penicillamine side-effects - one patient after nine months (marked anorexia, lassitude) and one other patient after 19 months (thrombocytopenia). Two patients died during the study, in one of these normal hepatic copper concentration was achieved. Hepatic copper concentrations decreased in seven of eight patients from 8.6 (2.7 +/- 16.2) mumol/g to 3.4 (0.6-16.5) mumol/g (median and range (0.05 less than 0.01) and serum aspartate transaminase increased in seven of eight patients (p less than 0.05). Histological assessment of serial liver sections revealed increased fibrosis and cholestasis despite reductions in hepatic copper levels during the study. This study showed that D-penicillamine therapy was associated with significant side-effects, while marked clinical, biochemical, or histological improvement did not follow effective copper chelation therapy in intrahepatic cholestasis of childhood.

Adolescent↗

PubMed1983

Significance of delta agent infection in chronic hepatitis B virus infection: a study in British carriers.

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease.

Adolescent↗

PubMed1983

Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy.

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative.

DNA-Directed DNA Polymerase↗

PubMed1983

Acute fatty liver of pregnancy and the microvesicular fat diseases.

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Acute Disease↗

PubMed1983

Acute type A, B, and non-A, non-B hepatitis in a hospital population in London: clinical and epidemiological features.

The aetiology of acute viral hepatitis in 172 patients admitted to an infectious diseases hospital in North London was: hepatitis A in 88 (51%), hepatitis B in 58 (34%), Epstein-Barr (EB) virus in four (2%) and non-A, non-B in 22 (13%). NANB hepatitis was a milder disease than that associated with the other viruses. It predominantly occurred in young men (77%). In half of the cases there was evidence of parenteral transmission. It was not transmitted by sexual contact.

Acute Disease↗

PubMed1983

Different hepatitis B vaccines.

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Hepatitis B↗