|Year : 2012 | Volume
| Issue : 2 | Page : 160-162
Salmonella Hepatitis: An Uncommon Complication of a Common Disease
Ritu Karoli, Jalees Fatima, Ashok Chandra, Gagandeep Singh
Department of Medicine, Era's Lucknow Medical College, Sarfarazganj, Lucknow, Uttar Pradesh, India
|Date of Web Publication||20-Dec-2012|
Department of Medicine, Era's Lucknow Medical College, Sarfarazganj, Hardoi Road, Lucknow,Uttar Pradesh - 226003
Typhoid fever is a very common infectious disease of tropics, associated with high morbidity and mortality. Typhoid fever is often associated with hepatomegaly and mildly deranged liver functions; a clinical picture of acute hepatitis is a rare complication. We report a young patient who presented with fever and jaundice and was found to have acute hepatitis secondary to typhoid fever. Recognition of Salmonella hepatitis is of clinical importance as it can mimic acute viral hepatitis. Early institution of specific therapy can improve the prognosis in these patients.Typhoid fever is a very common infectious disease of tropics, associated with high morbidity and mortality. Typhoid fever is often associated with hepatomegaly and mildly deranged liver functions; a clinical picture of acute hepatitis is a rare complication. We report a young patient who presented with fever and jaundice and was found to have acute hepatitis secondary to typhoid fever. Recognition of Salmonella hepatitis is of clinical importance as it can mimic acute viral hepatitis. Early institution of specific therapy can improve the prognosis in these patients.
Keywords: Enteric fever, Salmonella hepatitis, Salmonella typhi, typhoid fever, typhoid hepatitis
|How to cite this article:|
Karoli R, Fatima J, Chandra A, Singh G. Salmonella Hepatitis: An Uncommon Complication of a Common Disease. J Fam Med Primary Care 2012;1:160-2
|How to cite this URL:|
Karoli R, Fatima J, Chandra A, Singh G. Salmonella Hepatitis: An Uncommon Complication of a Common Disease. J Fam Med Primary Care [serial online] 2012 [cited 2014 Mar 12];1:160-2. Available from: http://www.jfmpc.com/text.asp?2012/1/2/160/104992
| Introduction|| |
Typhoid fever is a very common infectious disease of tropics, associated with high morbidity and mortality.  It usually starts as an acute systemic disease without localization, and is clinically indistinguishable from other infections, including malaria, bacterial, and viral infections. Multiple organs are known to be affected by the disease. Hepatic involvement could be considered important, as it may be associated with a higher relapse rate. , Typhoid fever is often associated with hepatomegaly and mildly deranged liver functions; a clinical picture of acute hepatitis is a rare complication. We report a young patient who presented with fever and jaundice and was found to have acute hepatitis secondary to typhoid fever.
| Case Report|| |
A 16-year-old male patient presented in medical outpatient department with history of high-grade fever with chills and an ill-defined abdominal pain of 7 days duration in October 2011. There was no history of cough, chest pain, dyspnea, dysuria, skin rashes, pruritus, dark color urine, clay color stool, or any hemorrhagic manifestations. He had no significant history of medical illness, drug ingestion, surgical procedures, blood transfusion, sexual promiscuity, and intravenous drug abuse or alcohol consumption. On examination, he was ill looking, mildly dehydrated, and febrile. He had tachycardia with normal blood pressure and respiration. Abdominal examination revealed soft, tender liver, 2 cm palpable below the costal margin at the midclavicular line. Rest of the general and systemic examination was unremarkable. His laboratory investigations showed borderline leukopenia (3800/mm 3 ). Peripheral smear for malarial parasite was negative. Biochemical evaluation showed normal renal functions and electrolytes, albumin, and coagulation parameters. Transaminases were elevated with aspartate aminotransferase (AST) 263 U/l, alanine aminotransferase (ALT) 382 U/l, and alkaline phosphatase (ALP) 126 U/l. Total and conjugated serum bilirubin were1.8 and 1.2 mg/dl, respectively. The blood, urine cultures, hepatic viral markers and serology for enteric fever, dengue and leptospirosis were sent. The patient was treated empirically with antimalarials chloroquine + lumifantrine and flouroquinolone (levofloxacine). Two days later, he was admitted in the emergency ward with vomiting and continuation of high-grade fever. His liver enzymes showed worsening (AST level was 792 U/l and ALT level was 1247 U/l). The icterus was apparent clinically, with a total bilirubin level of 3.6 mg/dl. The serum ALT: Lactate dehydrogenase (LDH) ratio (expressed in multiples of upper limit of normal) was found to be less than 9. The serology for viral hepatitis, dengue, and leptospirosis sent earlier was negative.Widal test was strongly positive in 1:640 dilution for both "O" and "H" antigens. Patient was treated with ceftriaxone 1 g intravenous twice daily and azithromycin 1g oral daily for 1 week. His blood culture yielded a growth of Salmonella typhi after 5 days incubation, with antibiotic sensitivity to ciprofloxacin (MIC < 0.5 mg/l) and ceftriaxone (<0.25 mg/l). The strain was resistant to ampicillin and amoxicillin + clavulinic acid. With treatment, the patient showed rapid clinical improvement along with decline in liver transaminases levels. He was discharged after 7 days of hospitalization.
| Discussion|| |
Typhoid fever continues to be a common infection in the developing countries. William Osler initially reported hepatic involvement of typhoid fever in 1899.  Hepatomegaly and moderate elevation of transaminase levels are the common findings that occur in 21-60% of cases , of typhoid fever. However, severe hepatic derangement simulating acute viral hepatitis is very rare. The presentation with marked elevation of transaminases similar to that of acute viral hepatitis, as observed in this case, has been reported by others. ,, Recognition of this clinical condition is particularly important in tropical countries where malaria and viral hepatitis are quite common. El-Newihi et al. did a retrospective analysis to compare clinical, biochemical picture, and the outcome of patients with Salmonella hepatitis and acute viral hepatitis. They concluded that the clinical picture of Salmonella hepatitis is frequently indistinguishable from that of viral hepatitis. Other clues that raise the possibility of Salmonella hepatitis include high fever, relative bradycardia, and left shift of WBCs. Despite long hospitalization, Salmonella hepatitis responds to proper antibiotic therapy and has an excellent prognosis.
The admission ALT/LDH ratio is the best discriminator between both entities, which was also advocated by Balasubramanian et al. in their study of 100 consecutive children with typhoid fever. The serum ALT: LDH ratio levels (expressed in multiples of upper limit of normal) was found to be less than 9 in typhoid hepatitis and more than 9 in acute viral hepatitis.
In viral hepatitis, nonspecific prodromal illness precedes jaundice and the fever usually subsides with the appearance of jaundice, while in typhoid, jaundice usually occurs within the first 2 weeks of febrile illness and the fever persists despite the appearance of jaundice. 
Pramoolsinsap et al. in their comprehensive review of Salmonella hepatitis suggested that typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with clinical features of acute hepatitis is a rare complication. The documented incidence varies widely from less than 1% to 26% patients with enteric fever. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of Salmonella infection. The factors predisposing to varying degrees of hepatic injury in typhoid fever are not exactly known. Possibly, there is an interplay of the micro-organism factors and the immunity, which cause liver injury.  The pathophysiological mechanism by which Salmonella produces hepatic dysfunction, although not fully known as yet, is postulated to be either due to direct invasion or by endotoxemia with immune-mediated liver damage. , Histopathologic study of the liver reveals typhoid nodules, cloudy swelling, ballooning degeneration, moderate fatty change, and mononuclear cell infiltrate in few focal areas. , In addition, intact bacilli have been demonstrated in the parenchyma of the liver by immunohistochemistry and have been cultured from liver biopsy. 
Although hepatitis-like picture with fever and jaundice is unusual and infrequently reported in the pediatrics literature,  in tropical areas, the differential diagnosis of a child presenting with fever and jaundice should include typhoid hepatitis. Cholestasis secondary to typhoid fever has only been reported in a few instances.  In a study of 254 patients with typhoid fever, Ahmad et al. found that clinical manifestations of typhoid fever are often non-specific and clinically indistinguishable from other infections, including malaria and other bacterial and viral infections, and can pose a significant diagnostic problem, especially in the tropics where jaundice in the febrile patient can be due to malaria, amebic or viral hepatitis. In many parts of the world, diagnosis is still based entirely on clinical features because conclusive laboratory confirmation of the infection is not usually available. They also reported significant rise in serum bilirubin without a corresponding increase in serum ALT, which is unusual in viral hepatitis but common in typhoid. So, typhoid should be considered in any febrile patient who develops jaundice about a week after the onset of illness and at the peak of fever with or without hepatomegaly. There are studies showing higher relapse rate associated with Salmonella hepatitis as compared to the general population. ,
Since typhoid fever is a common illness, the recognition of Salmonella hepatitis is of clinical importance as it can mimic viral, malarial, or amebic hepatitis. Early institution of specific therapy can improve the prognosis in these patients.
| References|| |
|1.||Khosla SN. Changing patterns of typhoid-A reappraisal. Asian Med J 1982;25:185-98. |
|2.||Khosla SN. Typhoid hepatitis. Postgrad Med J 1990;66:923-5. |
|3.||Nasrullah SM, Nassar VH. Enteric fever. Am J Gastroenterol 1978;69:63-9. |
|4.||Osler W. Hepatic complication of typhoid fever. Johns Hopkins Hosp Rep 1899;8:373-87. |
|5.||Ramachandra S, Godfrey JJ, Pevera MV. Typhoid hepatitis. JAMA 1974;230:236-40. |
|6.||Khosla SN, Singh R, Singh GP, Trehan VK. The spectrum of hepatic injury in enteric fever. Am J Gastroentrerol 1988;83:413-6. |
|7.||Morgatern R, Hayes PC. The liver in typhoid fever: Always affected, not just a complication. Am J Gastroenterol 1991;86:1235-9. |
|8.||Ramanathan M. Unusual hepatic manifestations in typhoid fever. Singapore Med J 1991;32:335-7. |
|9.||El-Newihi HM, Alamy ME, Reynolds TB. Salmonella hepatitis: Analysis of 27 cases and comparison with acute viral hepatitis. Hepatology 1996;24:516-9. |
|10.||Balasubramanian S, Kaarthigeyan K, Srinivas S, Rajeswari R. Serum ALT: LDH ratio in typhoid fever and acute viral hepatitis. Indian Pediatr 2010;47:339-41. |
|11.||Nazmul-Ahsan HA, Jalil-Chowdhury MA, Azharr MA, Rafiqeuddin AK. Pitfalls in the diagnosis of jaundiced patient in the tropics. Trop Doc 1995;25:191. |
|12.||Pramoolsinsap C, Viranuvatti V. Salmonella hepatitis. J Gastroenterol Hepatol 1998;13:745-50. |
|13.||Shetty AK, Mital SR, Bahrainwala AH, Khubchandani RP, Kumta NB. Typhoid hepatitis in children. J Trop Pediatr 1999;45:287-90. |
|14.||Ratnayake EC, Shivanthan C, Wijesiriwardena BC. Cholestatic hepatitis in a patient with typhoid fever-a case report. Ann Clin Microbiol Antimicrob 2011;10:35. |
|15.||Ahmed A, Ahmed B. Jaundice in typhoid patients: Differentiation from other common causes of fever and jaundice in the tropics. Ann Afr Med 2010;9:135-40. |