Abstracts of Papers Presented at the 66th Research Meeting of The Medical Research Centre of Bombay Hospital on Monday, 19th April 1999, 2.30 pm in The SP Jain Cafeteria
(Convenor Dr. HL Dhar)
1. ROLE OF AUTOIMMUNITY IN NONVIRAL CHRONIC LIVER DISEASE
DN Amarapurkar, AD Amarapurkar
Objective : To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease.
Methods : 435 consecutive patients with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination, liver function tests, ultrasonography, isotope liver scanning, viral markers, Autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Work up for Wilson’s disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Of the 435 patients 20 met the criteria of definite autoimmune hepatitis and 7 probable autoimmune hepatitis. 40 to 408 patients showed markers of autoimmunity positive but did not qualify for diagnosis of AIH on composite scores.
Results : Demographic profile of 27 patients with autoimmune hepatitis was as follows male : female 1:8; mean age 39.8 ± 13 years (Range 4-65 years) mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferase levels were 249 ± 343 and 262 ± 418 respectively. Other disease association seen was as follows: diabetes 4 (14.8%), rheumatoid arthritis 3 (11%) hypothyroidism 2 (7.4%) and ulcerative colitis 1 (3.7%). Pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children) ASMA +ve 16/27 (59.2%) (+ve titres of ASMA > 1:40) and Lkm1 in 3 patients. AMA in titres less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%) bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50%).
Conclusion : Autoimmune liver disease is not uncommon in India. Should be suspected in all patients of chronic liver disease especially non-viral, non-alcoholic female patients. Diagnosis of AIH should be done on composite scoring system given by international group and not on only presence or absence of autoimmune markers.
2. RAISED ALPHA-FOETOPROTEIN BUT NO STRUCTURAL LESION IN THE LIVER
Deepak N Amarapurkar
Alfa-foetoprotein (AFP) is synthesized by the embryonic liver and is a major protein normally found in foetal serum and disappears from blood soon after the birth. In normal adult AFP can be detected up to 20 ng/ml. Elevated AFP levels can be found in viral hepatitis, cirrhosis in 20 to 40% patients, but levels are generally less than 100 ng/ml. AFP levels above 400 ng/ml are specific for diagnosis of hepatocellular carcinoma. Bit sensitivity of AFP elevation above 400 ng/ml is around 50% for medium and large HCC and 10 to 20% small HCC. AFP has been suggested as marker for screening of HCC in high risk groups. As individuals with chronic liver disease who are at risk of developing HCC have elevated AFP in the absence of HCC. There are no guidelines as to when an elevated AFP levels in the presence of normal ultrasound should trigger further investigations to exclude HCC. Lok et al have observed elevated AFP levels in Chronic hepatitis B infection with differentiating benign from malignant lesions was difficult and thus proposed AFP monitoring alone is far from satisfactory for screening. As contrast to this Oka et al found elevated AFP levels more than 20 ng/ml when followed up carefully showed super high risk group for hepatocellular carcinoma. We evaluated 325 patients with chronic liver disease at the entry with AFP and ultrasound. Out of the 325, 35 patients had elevated AFP at the entry, 4 patients had elevated AFP more than 1000 ng/ml and large HCCs on ultrasound. One patient had moderate size HCC and AFP level of 120 ng/ml, 3 patients had small HCC with normal AFP levels. Of 30 patients with elevated AFP, 25 patients had AFP levels less than 100 ng/ml and no structural lesion on ultrasound. All these patients had elevated transaminases, 5 patients had AFP levels between 100 and 400 ng/ml; and normal transaminases and no structural lesions on ultrasound. All these patients are followed every six monthly with AFP and ultrasound. Only one patient in 2nd group showed HCC 3 years later. Ten patients died during follow up period, 4 due to variceal bleeding and 6 due to liver cell failure. Elevated AFP levels (in the absence of structural lesion) more than 400 ng/ml warrant further investigation urgently to exclude HCC while levels less than 100 ng/ml if associated with active hepatitis may not deserve further work up for HCC. Those with elevated AFP but normal transaminases should be carefully followed up to diagnose HCC at the earliest.
3. BALLOON ANGIOPLASTY IN BUDD CHIARI SYNDROME
DN Amarapurkar, SS Sharma
Background : Budd-Chiari syndrome (BCS) due to membranous obstruction of inferior vena cava (IVC) or hepatic veins are curable causes of portal hypertension. Percutaneous balloon angioplasty is simple, effective technique for treatment of these disorders. Compared to surgery morbidity and mortality associated with angioplasty is negligible.
Material and Methods : Over a period of last 7 years 53 cases of Budd-Chiari syndrome were seen. 34 cases of BCS were due to IVC and/or hepatic venous obstruction. Out of 34 cases eight patients had IVC membrane only, six patients had membranes in the IVC and one of the hepatic veins, six patients had IVC membrane with super added thrombosis, three patients had extensive IVC thrombosis, two patients had coarctation of the IVC, five patients had IVC obstruction due to invasive hepatocellular carcinoma, four patients had hepatic venous thrombosis. Diagnosis was based on clinical history, physical examination, duplex doppler and histology whenever necessary, IVC gram and hepatic venography was done in all patients except patient with HCC.
Results : All patients with only membranous obstruction were treated successfully with percutaneous transfemoral catheterization with excellent results. Two to seven years follow up in these patients showed complete regression of anterior abdominal wall collaterals reduction in size of liver, spleen and disappearance of oesophageal varices. Only three patients with membranous obstruction of IVC alongwith hepatic venous obstruction could be successfully treated. Four patients with membranous obstruction of IVC with superimposed thrombosis were treated with streptokinase infusion in IVC followed by balloon angioplasty. There was no procedure related mortality and morbidity in any of our patients.
Conclusion : Percutaneous balloon angioplasty is very safe and effective treatment in selected patients and should be offered to them.
4. HEPATITIS C INFECTION - WHOM SHOULD WE TREAT?
Hepatitis C infection though a heterogeneous disease is definitely a pernicious disease and is responsible for considerable mortality and morbidity. At this infection leads to significant morbidity and mortality it is essential to treat this infection. Interferon is only approved therapy for hepatitis C infection given in a dosage of 3 mu on alternate day for 12 to 18 months. Even with this regime sustained response rates are far from satisfactory. Combination of Ribavirin + interferon seems to be more promising than interferon alone. The goal of interferon treatment is to eradicate virus, achieve improvement in histology; to halt the progression of disease to cirrhosis and hepatocellular carcinoma and reduce the morbidity and mortality associated with this infection. Sustained response to standard interferon regimen is 20% and may increase to 30 to 40% in patients treated with combination of interferon + Ribavirin. Though sustained response rates are low, is associated with significant improvement in biochemical profile, histology and patient remain virus free in serum and liver suggesting cure of infection. There is evidence to show reduction in development of HCC. Favourable response to interferon is correlated to some degree with patient’s feature and virological characteristics. Young age, absence of cirrhosis and fibrosis on histology, short duration of disease, low hepatic iron stores, viral genotype other than 1, absence of quasispecies, low HCVRNA levels are predictors of good response. NIH consensus panel recommended therapy for adult patients with elevated serum transaminase levels, HCVRNA in the serum and liver biopsy showing fibrosis or at least moderate degrees of inflammation and necrosis. Therapy is not recommended for patients with decompensation, normal transaminase levels, children and patients above 60 years of age. In our experience only 40% patients with hepatitis C infection attending hospital are eligible for treatment. Of these eligible patients only 50% patients take and complete the interferon treatment. Remaining patients do not take treatment for economic constraints and 10% patients do not tolerate treatment.
5. A COMPARATIVE STUDY OF ENDOSCOPIC VARICEAL LIGATION (EVL), ENDOSCOPIC SCLEROTHERAPY (EST) AND COMBINATION (EVL + EST) THERAPY IN THE MANAGEMENT OF OESOPHAGEAL VARICES
DN Amarapurkar, SP Chouhan, PP Kulshreshtha, R Baijal, S Agal
Aim : Open label, nonrandomized comparison on EVL, EST and combination treatment in management of variceal bleed.
Methods : 55 patients (48 males, 7 females with mean age of 46 years) of cirrhosis of liver (50), extrahepatic venous obstruction (2) and noncirrhotic portal fibrosis (2) who presented with variceal bleed were subjected to either EVL (230) EST (20) or combination (12) treatment.
EVL + EST (12)
No. of sessions 2 ± 0.2 3.2 ± 1.3 2.5 ± 0.5 End points eradication 6 12 10 Two grade reduction in size 17 8 2 FU in months mean (Range) 6.4 ± 3.4 (1-12) 12.6 ± 3.8 (6-12) 5.1 ± 1.6 (1-12) Complications — 3 1 Rebleeding 3 5 2 Recurrence 3 2 0 Death 3 2 0
Conclusions : The combination therapy is significantly better in eradicating the varices as compared to EST or EVL alone. The untoward events (rebleeding), complications and death) were significantly less in combination therapy group versus others.
6. MORTALITY IN BOMBAY HOSPITAL - 6 YEARS STUDY
Atul Shah, HL Dhar
Hospital death records were analysed from 1993 to 98 including general parameters, duration of hospital stay and day on which patient died.
Total indoor admissions ranged between 25500 to 26700 showing almost constant 70 to 73 admissions per day. Total deaths through out six years varied from 650 to 750 in a year showing no significant change in death rate between 1993 (2.93%) and 1998 (2.45%). Deaths per day declined from 2.07 (1993) to 1.78 (1998). Male to female death ratio was 3:2, showing more mortality in males compared to females. Majority of the patients died within 2 to 15 days. Maximum deaths occurred in adults (50%) followed by elderly (33%). It is concluded that hospital data on mortality does not show any significant change during 1993 to 1998.
7. THYROID FUNCTIONS IN DIABETIC AND HYPERTENSIVE PATIENTS
DM Sharma, DR Jangid, SV Joshi, HL Dhar
This study was conducted to analyse thyroid functions in diabetic and hypertensive patients. Detailed clinical history was taken in 650 patients (F=480, M=170) reporting for thyroid function studies in Nuclear Medicine Department. T3, T4, TSH were measured, blood sugar was estimated in diabetic patients while urea, creatinine, cholesterol and urine catecholamines were measured in hypertensive patients to exclude secondary hypertension.
Thyroid function was found within normal limit in 454 patients (69.85%), 70 patients were hypothyroid (10.08%), and 126 patients (19.38%) were hyperthyroid. However, 44 (6.76%) were diabetic, 61 (39.6%) were hypertensive and 30 (4.6%), were suffering from both diabetes and hypertension.
In normal subjects (454) average thyroid functions were T3- 1.80 ± 0.8 ug/ml, T4 - 96.03 ± 8.6 ug/ml and TSH - 3.86 ± 1.1 mIU/ml. In hypothyroid (70) thyroid functions were T3 - 1.21 ± 0.67 ug/ml, T4 - 52.13 ± 5.2 ug/ml and TSH - 8.19 ± 2.18 mIU/ml in hyperthyroid subjects (126) thyroid functions were T3 - 3.29 ± 1.0 ug/ml T4 - 178.4 ± 8.3 ug/ml and TSH - 0.002 ± 0.01 mIu/ml.
Mean blood sugar in diabetic patients was fasting - 150 ± 20 mg/100 ml and post prandial - 248 ± 25 mg/100 ml. Biochemical profile in hypertensive patients were serum creatinine - 1.08 ± 0.06 mg%, cholesterol - 195.86 ± 5.24 mg%. Urea - 26.18 ± 3.21 mg% and urine catecholamines - 309.5 ± 5.96 ug/24 hrs.
No significant changes were seen in thyroid functions in hypertensive patients associated with thyroid disorders. However, significant decrease of T3 was documented in diabetic patients associated with thyroid disorders which could be due to decrease in the rate of conversion of T4 to both T3 and reverse T3 as well as decrease in the metabolic clearance rate of both triiodothyronines.
8. ROLE OF HDM SENSITIVITY IN EXERCISE INDUCED BRONCHOSPASM
SV Joshi, DM Tripathi, SY Bhave, HL Dhar
In the present study, 300 asthmatic children and 150 adults were studied. In both groups, approximately 63% were positive for house dust mite. According to lability Index 40% children exhibited exercise induced bronchospasm.
Based on preliminary study in children, detailed study was conducted in adults atopic and nonatopic asthmatics.
IgE mediated sensitivity to inhalant allergen was predominant 83% to HDM and 40% to pollen with overlapping in 23%. However, ingested allergens viz. food 67% were predominant in non IgE mediated sensitivity. Pulmonary functions were altered in atopic subjects compared to control. However, in both IgE and non IgE mediated mite sensitivity led to significant lowered pulmonary functions. Severity of asthma was directly proportional to mite sensitivity.
Exercise test did not show change in PFT, however, IgE mediated mite sensitivity led to EIB in 63% compared to 28% in non IgE mediated mite sensitivity suggesting that mite sensitization leads to EIB.
9. ALLERGENICITY OF THREE MOST COMMON POLLENS IN MUMBAI (INDIA) AND THEIR IMMUNOCHEMICAL CHARACTERIZATION
UD Mahadik**, PV Niphadkar*, HL Dhar**
*Sir HN Hospital, MRS, Mumbai 400 004. **MRC, Bombay Hospital Trust, Mumbai 400 020.Aerobiological study in Mumbai showed the highest prevalence of pollens of Borassus flabellifer (BF), Peltophorum ferrugineum (PF) and Typha angustata (TA) among the common airborne pollens. 559 patients were investigated for eosinophilia in blood and in nasal secretions. Total IgE estimations were carried out along with SPT, PFT, RT and nasal provocation with these pollen antigens. Out of total, 29 (5.1%), 31 (5.6%) and 38 (6.8%) patients were severely positive to BF, PF and TA respectively. Immunoblot analysis revealed 3 allergenic bands ranging from 80 to 206 KD showing specific IgE in BF, only one band at 76 KD in PF and two bands at 44 and 60 KD showing allergenicity of TA. In conclusion, our study has proved the allergenicity of these 3 pollens with characterized pollens.
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