Iain M. Murray-Lyon

Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A non-B hepatitis.

OBJECTIVE--To determine the effect of low dose interferon alfa (human lymphoblastoid interferon) on aminotransferase activities in chronic non-A non-B hepatitis. DESIGN--Prospective randomised controlled parallel group study of active treatment versus no treatment carried out over 16 weeks and preceded by baseline measurements at weeks 8 and 4 and time zero. SETTING--HEPATOLOGY outpatient clinics in secondary referral centres. PATIENTS--Fourteen adults with histologically proved chronic hepatitis and persistently raised aminotransferase activities for six months or more. INTERVENTIONS--Seven patients randomised to receive interferon alfa 5 megaunits (MU) daily for one week, reducing to 5 MU thrice weekly for seven weeks, then 3 MU thrice weekly for eight weeks. Controls not treated. END POINT--Control of hepatic enzyme activity in chronic non-A non-B hepatitis. MEASUREMENTS AND MAIN RESULTS--Serum aspartate aminotransferase activity remained raised in controls (mean increase in study period 23.4 U/l) but fell rapidly to normal in the treated group (mean decrease 106.4 U/l). In four cases values were normal by eight weeks and in five cases by 16 weeks. Only minor side effects were recorded (fever, myalgia), which became less common as treatment progressed. CONCLUSIONS--Continuous low dose interferon alfa reduces aspartate aminotransferase activity to normal in most patients with chronic non-A non-B hepatitis and may prevent progression to 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.

The effect of Qat chewing on blood pressure and heart rate in healthy volunteers.

The leaves of the Qat plant (Catha edulis Forsk., Celastraceae) which contain amphetamine like compounds are widely chewed in Yemen and East Africa for their pleasurable stimulant properties. There are also a number of unwanted side-effects and this paper studies the effect on heart rate and blood pressure in 80 healthy volunteers. During a 3-h period of chewing fresh Qat leaves there was a significant and progressive rise in systolic and diastolic blood pressure and heart rate, and levels had not returned to baseline 1h after chewing had ceased. Further studies are needed on possible cardiovascular morbidity associated with regular Qat chewing.

Hepatitis B virus DNA in the hepatocyte: a series of 160 biopsies

DNA-DNA hybridisation was used to examine 160 liver biopsies for the presence of the hepatitis B virus genome. HBeAg-positive HBsAg carriers were found to have replicating viral DNA in the hepatocytes and, very occasionally, HBV DNA was also integrated into the chromosomes. A high proportion of the anti-HBe-positive HBsAg carriers also have replicating HBV DNA and in the remainder integrated sequences are often, but not always, seen. No evidence was found, however, to implicate HBV in HBsAg-negative patients with alcoholic liver disease, nor in patients with a variety of other liver diseases including non-A, non-B hepatitis.

Further studies on streptozotocin therapy for a multiple-hormone-producing islet cell carcinoma

A patient with a multiple-hormone-producing islet cell carcinoma, who had previously been successfully treated with streptozotocin, was given three further infusions of this drug because of the redevelopment of gastric hypersecretion. Although some evidence of damage to the gastrinsecreting cells was obtained, the fasting plasma gastrin was not significantly altered and the patient died from a perforated duodenal ulcer. Serum insulin levels were considerably reduced and the patient became mildly diabetic but the main complication of treatment was a severe though reversible renal tubular defect. At necropsy considerable quantities of gastrin, but low levels of insulin and glucagon were extracted from a tumour metastasis.

Histological Sexing of a Reticulum Cell Sarcoma Arising after Liver Transplantation

Nuclear sex determination, based on both X and Y chromatin counts in a reticulum cell sarcoma which arose in the liver 5 months after orthotopic grafting, clearly showed that the tumor was of host origin. The Kupffer cells of the graft were also found to be of host origin, demonstrating that their replacement may occur within 6 months of operation.

Interferon plus amantadine versus interferon alone in the treatment of naive patients with chronic hepatitis C: a UK multicentre study

BACKGROUND/AIMS The antiviral agent amantadine may have activity against the hepatitis C virus. To determine whether the combination of interferon-alpha plus amantadine was more effective than interferon monotherapy we conducted a multicentre clinical trial in untreated patients with chronic hepatitis C infection. METHODS We performed a pilot study in two centres (36 patients) to determine the number needed for a statistically significant clinical trial and then conducted a multicentre, randomized controlled clinical trial involving 14 centres and 143 patients. RESULTS There was no significant difference in sustained response rates in patients receiving interferon and amantadine compared to those receiving interferon alone. The on treatment response rate at 3 months was 65% on combination vs. 49% on interferon alone (P = 0.05) while the sustained response was 18 and 15%, respectively. CONCLUSIONS Combination therapy with interferon plus amantadine does not lead to a significant increase in sustained response rates when compared to interferon monotherapy.

Noninvasive markers of fibrosis and inflammation in clinical practice: prospective comparison with liver biopsy.

Background The efficiency of transient elastography for the assessment of liver fibrosis has been evaluated mainly in patients with chronic hepatitis C and chronic hepatitis B, with few studies with nonviral chronic liver disease (CLD) such as autoimmune hepatitis, alcoholic liver disease and nonalcoholic steatohepatitis. In this study, we examined the value of transient elastography in a number of groups in comparison with the Fibrotest/Actitest (FT/AT), using the liver biopsy (LB) as the reference standard. Methods An unselected and consecutive group of 65 patients had an LB either as part of an initial diagnosis or of a follow-up assessment, and in addition had a transient elastography measurement [Fibroscan (FS)] and serum blood tests FT/AT performed before the LB. The group consisted of patients diagnosed with a variety of CLD: chronic hepatitis C (n=27), chronic hepatitis B (n=8), alcoholic liver disease (n=14), autoimmune hepatitis (n=13) and nonalcoholic steatohepatitis (n=4). Results FS optimal cutoff values were 9.70 kPa for F at least 2, 13.00 kPa for F at least 3, and 16.00 kPa for F=4. The areas under the receiver operating characteristic curve of FS and FT for F at least 2 were 0.88 versus 0.78 in the viral CLD group and 0.81 versus 0.70 in the nonviral CLD group and 0.87 versus 0.80 in all patients. The areas under the receiver operating characteristic curve for A at least 2 in all patients was 0.83. The optimal cutoff for A at least 2 was 0.50. Conclusion FT/AT is a reliable method for predicting significant liver fibrosis and necroinflammation in both viral and nonviral CLD patients with a value measurement comparable with that of the FS.

Preventing alcohol related birth damage: a review

Since 1974 numerous clinical studies have made it clear that heavy alcohol consumption during pregnancy (in excess of 80 g or 8 units daily) can result in a child being born with a specific combination of physical and mental disabilities known as the Fetal Alcohol Syndrome. More moderate levels of intake (as little as 10 g of 1 unit daily) are associated with other fetal problems known as Fetal Alcohol Effects. The most common of these is growth retardation. Reduction of alcohol consumption is beneficial to pregnancy outcome. However, despite this great clinical and research interest within the field there has been comparatively little attention paid to researching possible preventative strategies and appropriate policy development. This paper first describes the size of the problem posed by drinking in pregnancy in the U.S.A. and the U.K., detailing the contrasting policy response on either side of the Atlantic. It examines the difficulties of formulating appropriate advice and then assesses the available research reports on preventative measures. The strategies described include general publicity and counselling for pregnant women. In addition, attention has been paid to the problems of dissemination by emphasising professional education. One major shortcoming is that most of these studies appear to have been carried out with little reference to existing knowledge on health education and promotion, or educational work in the antenatal or alcohol fields. In addition, little attention appears to have been paid to the characteristics of the groups at whom intervention might be targeted or the underlying social or psychological factors which maintain drinking in these groups. The second part of this paper, therefore, attempts to suggest appropriate avenues for developing preventative strategies by presenting a wide-ranging review with special reference to British experience. Particular attention is given to the issues of form and content of appropriate messages, targeting of risk populations, the venue for intervention, and media and the actual mechanisms involved in implementing the programme. We conclude that women should be advised to limit their alcohol consumption to no more than one unit a day when they are either pregnant or planning a pregnancy. We recommend that pregnant women should be asked about their alcohol and given appropriate advice during routine antenatal clinic visits. We suggest that the form of advice should be designed with the characteristics of the risk population in mind.(ABSTRACT TRUNCATED AT 400 WORDS)

Prognostic value of serum alpha-fetoprotein in fulminant hepatic failure including patients treated by charcoal haemoperfusion.

Serum alpha-fetoprotein (AFP) levels have been measured sequentially by a radio-immunoassay method in 64 patients with fulminant hepatic failure. In 15 of the 64 patients (23%) AFP levels were raised but in only two did they exceed 500 ng/ml. Of the 23 survivors 11 (48%) had raised AFP levels compared with four of the 41 (9-8%) fatal cases (P less than 0-005). This rise in AFP levels was found early after the development of grade IV coma and constitutes an encouraging prognostic sign at a time when the liver function tests and EEG are unhelpful. A radioimmunoassay must be used if these small but significant rises in plasma concentration are to be detected. Twelve patients survived without showing a rise in plasma AFP at anytime during the illness. The four fatal cases who had raised AFP levels all had serious complications of fulminant hepatic failure. Charcoal haemoperfusion did not seem to increase the survival of AFP negative patients.