Abdul Baqi Durrani  ( Department of Medicine, Bolan Medical College, Quetta. )

Typhoid Hepatitis is a rare presentation of typhoid fever, clinically suspected in patients with persistent fever hepatomegaly and jaundice and especially in cases where the liver function tests show predomi­nantly conjugated hyperbilirubinemia, modest elevation of liver enzymes and negative serology for viral hepatitis. From January, 1989 to December, 1994, 476 cases were included in this study, 204 with typhoid fever admitted in JPMC Karachi and 272 in Civil Hospital, Quetta. Eleven percent cases had typhoid hepatitis. Nineteen (4%) cases were initially diagnosed as viral hepatitis and 33(7%) developed jaundice later on. As typhoid is prevalent in Pakistan and typhoid hepatitis is a challenging problem, accurate and simple methods are required for diagnosis in all febrile cases. It should particularly be considered as a differential diagnosis for cases with fever, jaundice and hepatomegaly (JPMA 45 :317, 1995).

Mild jaundice and hepatomegaly have been reported in typhoid fever, which has a worldwide distribution¹. It is particularly prevalent in developing countries² due to lack of public health education and failure in communal hygiene³. It also becomes a challenging problem, when it presents atypi­cally and jaundice, fever and hepatomegaly is one such presentation which masquerades as infective hepatitis⁴. This study reports prevalence of typhoid hepatitis in cases of typhoid fever.

To determine the prevalence of typhoid hepatitis, all cases diagnosed primarily as typhoid fever and admitted to the Medical Unit of JPMC, Karachi and Civil Hospital, Quetta were included in the study. Pregnant females and patients taking drugs with known hepatotoxic side effects were excluded. Nineteen patients were diagnosed provisionally as hepatitis due to the presence of jaundice whereas 33 became distance at a later stage. A detailed physical examination was carried out Laboratory tests included a complete blood picture, urine analysis, blood urea, serum creatimne, blood smear for malarial parasite, Hepatitis B surface antigen and liver function tests: serology for hepatitis profile was per­formed when facilities were available. Blood and bone narrow cultures were done and widal test performed on admission and after 2 weeks. Liver biopsy was done in 12 cases only. Blood and bone marrow samples were collected simul­laneously and aseptically. Five ml of blood drawn with a disposable syringe was dispensed into culture bottles contain­ing 45 ml of brain heart infusion broth⁵. Similarly, bone marrow aspiration was done according to Keeling’s method⁶. About 1 ml of bone marrow aspirate from the syringe was directly transferred to the culture bottle containing 25 ml of ‘brain heart infusion broth’, which was incubated at 37°C for seven days. In the intervening period, sub-cultures were made every 24 hours (up to 72 hours) on sheep blood agar, Mac Conkey’s agarand Salmonella Shigella agar plates and then incubated at 37°C on the 7th day of incubation. Bacilli were further identified according to the standard techniques⁷. Antimicrobial sensitivity pattern of all the isolates was done by standard disc diffusion method⁵. The susceptibility or resistance was judged on the basis of measurement of zones of growth inhibition around individual discs.

A total of 476 cases were included in this study. Of these, 52 had typhoid hepatitis. Nineteen (4%) were initially diag­ nosed as viral hepatitis and 33 (7%) developed jaundice at a later stage. There were 31 males and 21 females with the maximum number of patients (13) being in the age group 10-20 years. Thirty-six subjects belonged to the poor socio-economic class. Most frequent symptoms were fever, headache, nausea, vomiting and abdominal discomfort. Main physical signs were fever, jaundice, tender hepatomegaly, splenomegaly, (41 cases) and toxemia. All patients had fever ranging between 100°F to 103°F. They developed moderate jaundice between 6-10 days. Laboratory investigations showed a raised ESR in 23 (44%) cases. No malarial parasite was reported in the blood smear and the serology for hepatitis was negative in all patients. Widal was positive in the 19 cases presenting as hepatitis giving a high suspicion of typhoid hepatitis. Blood culture was positive in 8 (42%) cases, while bone marrow culture was positive in all 19 cases. The remaining 33 cases presented as a febrile illness and developed jaundice and hepatomegaly at a later period. Bone marrow culture was positive in all cases, irrespec­tive of duration of pyrexia, jaundice and hepatomegaly. The predominant abnormality in the liver function test was a conjugated hyperbiirubinemia. The values ranged between 2.3 and 7.0 mg% with a mean value of 3.82 mg%. Total serum biirubin was more than 10 rng% in 5 patients with an overall mean value of 6.06 mg%. SGPT levels varied between 43.9 to 160 U/L (mean 91.44 U/L). The alkaline phosphatase was between 76.2 and 180 U/L (mean 14.78 UIL). Liver biopsy was done in 12 cases. All showed intact lobular architecture and swollen hepatocytes with dilatation of sinusoids, which were lined by plump hyperplastic Kupffer cells. Three biopsies done in the acute stage, showed mild mononuclear cell infiltration in the portal triad and the sinusoids contained a large number of mononuclear cells. Three specimens showed moderate fatty infiltration of hepatocytes with some areas of liver necrosis. All cultures were reported sensitive to of loxacin and ciprofloxacin which gave a 100% cure rate. There was no mortality.

Fever, jaundice and hepatomegaly is a common triad seen in medical outpatients in tropical countries like Paki­stan^8,9. The age in this study ranged from 10-70 years and fifty percent of cases occurred in persons less than 35 years of age which has been reported by other workers also¹⁰. Typhoid hepatitis was more common in males as compared to the females in a proportion of about 3:2. The initial clinical diagnosis of typhoid hepatitis is largely dependent on a high index of suspicion. The confirma­tion of the diagnosis of typhoid hepatitis still depends on laboratory investigations in most of the cases¹¹. In countries like Pakistan, where febrile illness with jaundice are com­monly encountered, it is vital, to carefully differentiate between viral hepatitis, malarial hepatitis and typhoid hepati­tis. As the treatment for viral hepatitis is only supportive, for the other two conditions, the treatment has to be prompt and specific.
In this study all 19 (4%) cases presenting with fever, jaundice and hepatomegaly were initially thought to haveviral hepatitis. However, the history of pyrexia ranging between 100°F to 103°F and appearance of moderatejaundice between 6 to .10 days gave a suspicion of typhoid hepatitis. This was supported by abnormal LFT’s and positive with test. It is concluded that typhoid should be considered in patients with persistent fever, jaundice and hepatomegaly, who show conjugated hyperbilirubinemia with mild derange-ment of enzymes and negative serology for viral hepatitis. Whether widal test should be used as a screening criteria for typhoid hepatitis in all patients presenting as hepatitis is a matter for speculation and further research because it only becomes positive in the second week of the typhoid fever¹². Jaundice is not a very common mode of presentation of typhoid fever but is not that rare either^13-15. Bone marrow culture is a helpful investigation as Salmonellae persist for prolonged periods in the RE cells of the bone marrow. This provides an early diagnosis^16,17. Liver histology shows non- specific changes and is therefore not recommended.

1. Mangal, H.N., Joshi, K.C. and Gupta, D.P. Prevalence of Ent. fever in Jaipur. indian J.Med. Res., 1967,55:219-23.
2. Khosla, S.N. Changing pattern of typhoid. Asian Med. J., 1982;25(3):185.98.
3. Siddiqui, S. Epidemiological pattern and control strategies in typhoid lever. J. Pak. Med. Assoc., 1991 ;6:143-46.
4. Manson, B. and Bell. Typhoid fever in Manson’s tropical disease, edited by Manson Bahr and Bell, 19th ed. Bailliere, Tindall, 1987, pp. 194-206.
5. Bauer, J.D. Clinical laboratozy methods, 9th ed., Saint Louis, The C. V. Mosby Company, 1982, pp. 825-28.
6. Keeling, R.P. Bone macrow aspiration and biopsy in manual of medical procedures, edited by Suratt, P. M. and Gibson, R. S. Saint Louise, The C. V. Mosby Company, 1982, pp. 232-33.
7. Bailey, W.R. and Scott, E.G. Diagnostic Microbiology, by Finegold, S. M. and Baron.E. J., 7th ed.,.Saint Louis, The C. V. Mosby Company, l986,pp. 186-219, 399-421.
8. Nasrullah, S.M. and Nassar, V.H. Enteric fever a clinicopathological study of 104 cases. Am. J. Gasttroenterol., 1978;69:63-66.
9. Sherlock, S. Diseases of the liver and biliary system. 8th ed. Oxford, Blackwell, 1989, pp. 567.68.
10. Johnson, A.O.K. and Aderele, W.I. Enteric fever in Childhood. J. Trop. Med. Hyg. 1981;84:29-35
11. Laditan, A.A.O. Problems in the clinical diagnosis of typhoid fever in children in the tropics. Ann. Trop. Paediatr., 1981;1:191-95.
12. Raymond, A., Smigo, Jr. and Bhutta, Z. A. Multiple drug resistant Salmonellae. J. Pak. Med. Assoc., 1987;37:212-15.
13. Karamat, K.A., Akhtar, M.A., Malik, IA. Multidrug resistant salmonella typhi in Northern Pakistan: Pak. J. Pathol. 1991 ;2:37-40.
15. Burke, A. and Cunha, M.D. Systemic infections affecting the liver. Postgrad. Med., 1988;84(5):148 -56.
16. Cheesbrough., J.S. and Rigby, A. Laboratory diagnosis of Salmonella infections, Postgrad., 1989;12:348-58.
17. Hoffman, S.L., Edman, D.C., Punjabi, N.H. et al. Bonemarrow culture superior to streptokinase clot culture and blood culture for diagnosis of typhoid fever, Am. J. Trop. Med. Hyg., 1986;35:836-39.