Need for liver biopsy in alcoholic liver disease.
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Biomedical subjects
Publications and source records attributed to G Bird.
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An alcohol intake of more than 35 units per week will predispose to alcoholic liver disease, although not all patients with alcohol-induced liver damage have a dependency syndrome and only about 20% of those with an unremitting heavy alcohol intake will develop liver disease. In those with evidence of chronic liver disease, a liver biopsy is the most important investigation because it confirms the diagnosis and is indicative of the prognosis. Abstinence remains the mainstay of treatment and a multi-disciplinary approach is the best way to achieve this in most cases. In patients with severe alcoholic hepatitis, specific therapies such as high dose corticosteroids and propylthiouracil have shown promising results but are still under evaluation. Liver transplantation has been used successfully in patients with recurrent complications arising from portal hypertension, but whether a minimum period of abstinence should be a requirement remains the subject of debate.
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In a randomized, controlled trial to investigate the possible benefit of insulin and glucagon therapy in severe acute alcoholic hepatitis, 86 patients were randomized to receive 30 U insulin and 3 mg glucagon in 250 ml 5% dextrose over 12 hr each day for 3 wk or a similar regime of identical placebo. No significant differences were seen in patients' clinical characteristics and disease severity in the treated and placebo groups. Of the 43 patients receiving insulin and glucagon, 15 (35%) died within 4 wk of randomization, compared with 14 deaths (33%) in the control patients (p = not significant). When the patients surviving the first 4 wk were examined there were five more deaths in the treatment group, compared with one death in the control group at 6-mo follow-up (p = not significant). No significant differences in the frequency of short-term or long-term complications of alcoholic liver disease or relapse to alcohol were seen when the two groups were compared, although hypoglycemia was seen in six patients during infusion of insulin and glucagon. Similarly, no significant differences were seen in the improvement in clinical or biochemical features at 4 wk and at 6 mo in survivors when the insulin and glucagon-treated patients were compared with patients in the placebo group. This study does not confirm previous reports that insulin and glucagon infusion improves the outcome of severe acute alcoholic hepatitis.
Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
An immediate hypersensitivity reaction to seminal fluid is an uncommon but well recognized condition. We describe a young woman who developed haemorrhagic proctitis, arthralgia and urticaria on honeymoon. Investigations suggested an immune complex (type III) hypersensitivity. It subsequently became clear that her symptoms were temporally related to sexual intercourse. After 8 hours she developed nasal congestion and urticaria followed by migratory arthralgia and periorbital oedema. Over the ensuing 24 hours she had diarrhoea, occasionally with blood. She became breathless and had evidence of a restrictive ventilatory defect. These symptoms improved over 4-5 days. Further in vitro investigations were inconclusive but intradermal skin testing with seminal plasma led to recurrence of all her symptoms. Symptoms ceased with condom usage, and the condition abated over 2 years. This patient is unique in that seminal fluid hypersensitivity appears to have produced a type III immune response.
We have studied the effects of filtering mucus from bronchoalveolar lavage (BAL) fluid on its cellular contents. We examined BAL fluid from 18 patients without excessive endobronchial mucus, and from three patients with bronchiectasis. In the non-bronchiectatic subjects there was a fall of 18% in mean absolute cell count from 2.66 +/- SD 1.9 x 10(9) l-1 to 2.18 +/- 1.4 x 10(9) l-1 (P less than 0.05) as a result of filtration. This was due to a selective loss of macrophages and there were no significant changes in the absolute numbers of either lymphocytes or neutrophils. The differential macrophage count fell from a mean of 82 +/- 14% to 76 +/- 16%, while the mean differential lymphocyte count rose from 14 +/- 7% to 19 +/- 9% and the mean differential neutrophil count increased slightly from 4 +/- 4% to 5 +/- 4%. In the three patients with bronchiectasis the absolute cell counts were grossly raised, due almost entirely to an excess of neutrophils. In these patients, filtration reduced the absolute macrophage count by 61% and the absolute neutrophil count by 27%. Overall, change in absolute cell count correlated significantly with mucus volume (r = 0.76, P less than 0.05). Removal of mucus by filtration affects absolute cell count and may have a selective effect on cell numbers. If filtration of BAL fluid is unavoidable, its effect on cell counts should be clearly established if data from different centres are to be meaningfully compared.
Bronchial responsiveness to methacholine (PD20 FEV1) was assessed in 22 asthmatic subjects approximately 5 days prior to bronchoalveolar lavage (BAL). A PD20 FEV1 could not be attained in 20 matched controls with normal pulmonary function. BAL was performed in all subjects, 3 x 60 ml aliquots of buffered saline being introduced into a segment of the middle lobe and immediately aspirated into siliconized glassware at 4 degrees C. After filtration, cells were counted, and the cell pellet resuspended in medium 199. Cytospin slides were prepared and a differential cell count performed. Lymphocyte subsets were identified by labelling further cytospin preparations with specific monoclonal antibodies (Leu series) against T3, T4, T8 and B cell markers, followed by a fluorescent antibody marker. The slides were coded, and 100 lymphocytes were then randomly scanned for fluorescence on each cytospin preparation. The median total lymphocyte counts were significantly greater in the asthmatic subjects, but this increase was confined to the T cell subgroups. The mean T4/T8 ratio was similar in asthmatic (1.51) and control (1.45) subjects. Log PD20 FEV1 correlated positively with total lymphocyte counts (r = 0.42, P less than 0.05), and with total T8 counts (r = 0.60, P less than 0.05). Correlations between bronchial responsiveness and T3, T4 and B lymphocyte numbers all failed to reach significance, and there was no correlation with T4/T8 ratios. The increase in BAL lymphocyte counts in asthma appears to be due to an absolute increase in T cell subsets, especially the T8 lymphocyte subgroup, and is most marked in mild asthmatics.
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Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers). The asthmatic patients had a baseline FEV1 greater than 60% predicted and a PD20FEV1 (provocative dose of methacholine causing a 20% fall in FEV1) of 0.006-3.7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV1 above the maximum cumulative dose of methacholine of 6.4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p less than 0.05) and lymphocyte (p less than 0.005) counts in asthma. PD20FEV1 was negatively correlated with percentage neutrophil counts (p less than 0.005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p less than 0.001), but was not correlated with PD20FEV1 Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p less than 0.001) and showed a negative correlation with PD20FEV1 (p less than 0.01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.
Intermediate dose intravenous melphalan at a dose of 15 mg/m2 x 4 given at 21-day intervals has been evaluated in 20 consecutive patients. The aims were to assess the time to obtain maximal response, duration of response and response to reintroduction of intravenous melphalan on relapse. Median time to maximal response was 17 weeks. Four patients achieved a complete response with complete disappearance of paraprotein. On relapse, reintroduction of intravenous melphalan was unsuccessful in causing a reduction of paraprotein, suggesting that resistance to this dose of melphalan occurs early even in responding patients.
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A representative sample of 49 women (40-59 years) in Caerphilly, South Wales, completed a seven-day weighed dietary record and a similar sample of 48 women photographed all food and drink consumed for seven days. Mean nutrient intakes calculated for the two methods were very similar, indicating that the photographic method is reliable. Mean energy intake for the 97 women was 6.6 MJ/d (1568 Kcals). Mean intakes of protein fat and carbohydrate were 56 g, 72 g and 179 g per day respectively. Intakes were comparable with those reported from another survey in South Wales, but considerably lower than those reported from a study in Cambridgeshire. Possible reasons for these differences were discussed.
One hundred and forty-three multitransfused patients with hereditary haemostatic disorders were examined for evidence of disease related to the acquired immune deficiency syndrome (AIDS). Ninety-nine patients with severe haemophilia A were tested for anti-HTLV-III and 76 were found to be positive. All except one of these seropositive patients had received commercial factor VIII concentrates at some time. Eighteen patients with haemophilia B were tested and all were anti-HTLV-III negative. Three out of 36 sexual partners of patients with haemophilia A positive for anti-HTLV-III were also seropositive. One, who had recently received blood transfusions, had AIDS with Pneumocystis carinii pneumonia. Three patients with severe haemophilia A died from Aids. A further 30 haemophiliacs had AIDS related complex or lymphadenopathy that could be related to HTLV-III infection. There was a significant correlation between lymphadenopathy and anti-HTLV-III seropositivity. No evidence of casual spread of AIDS was found since all 68 health care staff tested were anti-HTLV-III negative, including three surgeons who regularly worked with patients positive for anti-HTLV-III. The resources devoted to counselling and laboratory support in centres treating people at risk and their families need to be urgently reassessed.
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A photographic method of diet evaluation was compared with a weighed record recording method in seventeen subjects. All subjects found the method easy and acceptable though one subject failed to use the method correctly. For the others the two methods gave very similar results, the difference for no nutrient was statistically significant.