Case Report
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 28, 2006; 12(32): 5253-5255
Published online Aug 28, 2006. doi: 10.3748/wjg.v12.i32.5253
Fulminant hepatic failure caused by Salmonella paratyphi A Infection
Fahmi Yousef Khan, Ahmed A Kamha, Ibrahim Y Alomary
Fahmi Yousef Khan, Ahmed A Kamha. Ibrahim Y Alomary, Department of Medicine, Hamad General Hospital, Doha, Qatar
Author contributions: All authors contributed equally to the work.
Correspondence to: Fahmi Yousef Khan, MD, Senior specialist, Department of Medicine, Hamad General Hospital, PO Box 3050, Doha, Qatar. fakhanqal@yahoo.co.uk
Telephone: +974-5275989 Fax: +974-4879228
Received: April 26, 2006
Revised: July 15, 2006
Accepted: July 22, 2006
Published online: August 28, 2006

Abstract

We report a case of fulminant hepatic failure associated with Salmonella paratyphi A infection, in a 29-year-old patient who was admitted to the intensive care unit (ICU) with fever of two days, headache and vomiting followed by behavioural changes and disorientation. On examination, the patient appeared acutely ill, agitated, confused, and deeply jaundiced. Temperature 38.5°C, pulse 92/min, blood pressure 130/89 mmHg. Both samples of blood grew S. paratyphi A, which was sensitive to ceftriaxone and ciprofloxacin. Ceftriaxon was administered with high-dose dexamethasone. Two weeks after treatment with ceftriaxon, the patient was discharged in satisfactory condition.

Key Words: Typhoid hepatitis, Fulminant hepatic failure, Salmonella paratyphi A



INTRODUCTION

Fulminant hepatic failure is a dramatic clinical syndrome characterized by massive necrosis of liver cells[1]. It is caused by acute viral hepatitis A, B, C, D, E (40%), other viruses, drugs, Weil's disease, Wilson's disease, acute fatty liver in pregnancy, ischemic hepatitis, acute Budd-Chiari, malignant infiltration or bacterial infection including salmonella.

Although salmonella hepatitis is a rare presentation of typhoid fever, fulminant hepatic failure is extremely uncommon, few cases were reported with such presentation. To our knowledge, this is the first reported case of fulminant hepatic failure in the state of Qatar, associated with Salmonella paratyphi A infection.

CASE REPORT

A 29-year-old Nepali male patient admitted to the intensive care unit (ICU) through accident and emergency (A&E) department with fever for two days, headache and vomiting followed by behavioral changes and disorientation. The patient returned back from his country two months ago. No other history of possible relevance was found. On examination, the patient appeared acutely ill, agitated, confused, and deeply jaundiced. Temperature was 38.5°C, pulse 92/min, and blood pressure 130/89 mmHg. Examination of the nervous system showed a disoriented patient, moving all his limbs, with incoherent speech and negative meningeal signs. Examination of the abdomen revealed mild splenomegaly. Chest and heart were unremarkable. Hemoglobin level was 150 g/L, total leucocyte count 5000/μL (60% neutrophils, 31% lymphocytes) and adequate number of platelets. Blood chemistry showed asparate aminotransferase (AST) level of 966 IU/L, alanine amino-transferase (ALT) 176 IU/L, alkaline phosphatase 267 IU/L, total bilirubin 180 μmol/L, direct bilirubin 109 μmol/L, total proteins 74 g/L, albumin 38 g/L, urea nitrogen 3 mmol/L, creatinine 44 μmol/L, sodium 135 mEq/L and potassium 3.6 mEq/L, bicarbonate 22 mmol/L, Ca 2.2 mmol/L , ammonia level 100 μmol/L (normal up to 50 μmol/L), prothrombin time 30.8 s and an international normalized ratio (INR) of 3.1. Macroscopic and microscopic examination of urine and stool were normal. Viral markers for hepatitis A, B, C, Monospot test and cytomegaloirus serology were negative. Antismooth muscle antibody and antimithocondrial antibody were negative. Peripheral smear for malaria was negative on several occasions. Lumber puncture was done, and CSF study was normal.

Computerized tomography (CT) scan of the head with intravenous contrast was normal. Electroencephalography showed findings suggestive of metabolic encephalopathy. Chest X ray was normal. Ultrasonography of abdomen revealed enlarged spleen. Rest of abdomen including liver, gall bladder, and kidney were all within normal limits.

A CT scan of the abdomen, with intravenous contrast showed moderate spleen enlargement and liver enlargement with homogeneous parenchyma. There was no evidence of abscess or tumor. No evidence of mass or fluid collection was seen in the abdomen or pelvis. Kidneys and pancreas were within normal limits. Echocardiography was normal. Magnetic resonance image (MRI) of the abdomen with MR cholangiography showed peri-portal edema within the liver and collapsed gall bladder, suggesting the possibility of hepatitis.

The patient was admitted to the ICU as a case of fulminant hepatic failure evidenced by marked elevation of hepatocellular enzymes, prolonged prothrombin time, hyperbilirubinemia and hyperammonaemia. The patient was given vitamin k and fresh frozen plasma to correct the prolonged INR, and Lactulose (enema and oral). Broad-spectrum antibiotic and high dose dexamethasone (3 mg/kg loading dose over 30 min, followed by 1 mg/kg every six hours for two days) were initiated. Cultures of urine were sterile and no pathogen was isolated from stool culture.

However, both samples of blood grew S. paratyphi A, which was sensitive to ciprofloxacin and ceftriaxone. Once the culture report was available the treatment was changed to ceftriaxone 2 gm twice daily. After one week of therapy, the patient was afebrile and oriented, and the dose of ceftriaxon was reduced to 2 gm daily for one more week. Two weeks after treatment with ceftriaxon, the liver enzymes dropped obviously (Table 1). Consequently, the patient was discharged in satisfactory condition.

Table 1 Laboratory data on admission and discharge.
Alanineamino-transferase(ALT)Asparateaminotrans-ferase (AST)Alkalinephosphatase(ALP)Total bilirubin
On admission day176 IU/L966 IU/L267 IU/L180 μmol/L
On discharge day65 IU/L105 IU/L110 IU/L33 μmol/L
DISCUSSION

Typhoid fever may be an important cause of illness and death for centuries, although historical accounts do not clearly distinguish it from other febrile illnesses. It has been implicated in the death of Alexander the Great, in 323 B.C.[2].

The causative organism widely spreads in all parts of the world, although the disease is more prevalent in developing countries than in developed ones. The most common cause of typhoid fever is Salmonella enterica serotype typhi, although salmonella of other serotypes, particularly Salmonella enterica serotype paratyphi A, can cause a similar enteric fever. Salmonella enterica serotype typhi has no animal reservoir.

In typhoid, involvement of liver is a consistent feature[3,4]. Typhoid hepatitis is a rare presentation of typhoid fever, clinically suspected in patients with persistent fever , hepatomegaly and jaundice and especially in cases whose liver function tests show predominantly conjugated hyperbilirubinemia, modest elevation of liver enzymes and negative serology for viral hepatitis[5,6].

The differential diagnosis of fever in the icteric phase of hepatitis, include: viral hepatitis, malaria hepatitis, Weil’s disease, typhoid hepatitis, autoimmune hepatitis and drug induced hepatitis.

In this patient, viral markers for hepatitis A, B, C, Monospot test and cytomegalovirus serology were negative. Peripheral smear for malaria was negative on several occasions. Antismooth muscle antibodeis (Ab) and antimithocondrial Ab were negative and whether the patient had taken any hepatotoxic drugs was unknown.

The common complications of typhoid fever include relapse, perforation and hemorrhage from bowel ulcerations[3]. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis.

The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial, involving endotoxin, local inflammatory and/or host immune reactions.

In typhoid hepatitis, liver biopsy would have shown pathognomonic lobular aggregates of Kupffer’s cells-so-called typhoid nodules, but liver biopsy was not performed in this case[2].

Although, viral markers for hepatitis E and leptospiral test were not made in this case, the diagnosis of fulminant hepatic failure due to S. paratyphi was based mainly on three facts: first, positive blood culture for S. paratyphi A; second, elevated alkaline phosphatase level, aspartate aminotransferase (AST) level higher than alanine aminotransferase (ALT) , and only mild prolongation of the prothrombin time[7]; and third, excellent response to ceftriaxon and dexamethasone[7].

The most important aspect of treatment for typhoid fulminant hepatic failure is to provide good intensive care support, recognize the condition promptly and initiate early dexamethasone and proper antibiotics. Monitoring the complications and instituting appropriate therapy are also critical.

The current drug of choice for adults is ciprofloxacin, which combines little documented resistance with excellent penetration into macrophages and the biliary system. This may lower the rate of relapse and chronic carrier states. Alternative antibiotics can be used if sensitivities are known or suspected resistance is low[8]. The current drug of choice for children and pregnant women is parenteral ceftriaxone[9].

Thus, in patients from endemic areas, typhoid hepatitis should be considered in the differential diagnosis of fulminant hepatic failure since early institution of specific therapy in these cases yields a good prognosis.

Footnotes

S- Editor Wang J L- Editor Ma JY E- Editor Liu WF

References
1.  Bernuau J, Rueff B, Benhamou JP. Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis. 1986;6:97-106.  [PubMed]  [DOI]
2.  Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 22-2001. A 25-year-old woman with fever and abnormal liver function. N Engl J Med. 2001;345:201-205.  [PubMed]  [DOI]
3.  Forsyth JRL. Typhoid and paratyphoid. Topley and Wilson's. Microbiology and Microbial infections. 9th ed. London: Arnold Press 1998; 450-478.  [PubMed]  [DOI]
4.  El-Newihi HM, Alamy ME, Reynolds TB. Salmonella hepatitis: analysis of 27 cases and comparison with acute viral hepatitis. Hepatology. 1996;24:516-519.  [PubMed]  [DOI]
5.  Durrani AB. Typhoid hepatitis. J Pak Med Assoc. 1995;45:317-318.  [PubMed]  [DOI]
6.  Pandey CK, Singh N, Kumar V, Agarwal A, Singh PK. Typhoid, hepatitis E, or typhoid and hepatitis E: the cause of fulminant hepatic failure--a diagnostic dilemma. Crit Care Med. 2002;30:376-378.  [PubMed]  [DOI]
7.  Kamath PS, Jalihal A, Chakraborty A. Differentiation of typhoid fever from fulminant hepatic failure in patients presenting with jaundice and encephalopathy. Mayo Clin Proc. 2000;75:462-466.  [PubMed]  [DOI]
8.  Akalin HE. Quinolones in the treatment of typhoid fever. Drugs. 1999;58 Suppl 2:52-54.  [PubMed]  [DOI]
9.  Thomsen LL, Paerregaard A. Treatment with ciprofloxacin in children with typhoid fever. Scand J Infect Dis. 1998;30:355-357.  [PubMed]  [DOI]