Severe (complicated) hepatitis A in Cotonou (Benin) concern­ing an incompletely vaccinated Spanish expatriate

Summary

Viral hepatitis A is a major cause of acute hepatitis in the world. Its progression can be fulminant. Generally, it does not usually pose a major health problem among people living in endemic areas, but can be an important source of morbidity for unvaccinated subjects from western countries travelling in highly endemic areas. We report a severe case of viral hepatitis A concerning a patient of Spanish origin, incompletely vaccinated and recently immigrated in Benin. Two months before hospitalisation, she had an elective cholecystectomy for symptomatic cholecystolithiasis.

Key words:
jaundice –  hepatitis A –  expatriate –  incomplete vaccination

Introduction

Viral hepatitis A (HAV) is a major cause of acute hepatitis in the world [1]. Each year, there are more than 1.5 mil­lion new infections with hepatitis A worldwide [2]. The virus is transmit­ted via the faecal-oral route, usual­­ly through inter-human contact or from ingestion of food or contaminated water. The HAV is almost always asymp­tomatic in children under three years, but usual­ly symp­tomatic in adults and may be severe (complicated). Very rarely, the HAV may have a fulminant course which may lead to liver failure and death. In Sub-Saharan Africa (SSA), the HAV is endemic with more than half of all children (under five years) contaminated [3]. In endemic areas, the risk of contract­ing HAV is 90%, usual­ly in childhood. Subjects who once have contracted HAV are im­mune for life. This is why the World Health Organization recom­mends no systematic vaccination in people liv­ing in areas of high endemicity such as Africa [2,4]. However, subjects travel­­­­-l­­­ing from Western countries to SSA have a high risk of contract­ing the disease in the absence of vaccine protect­ion. We report a severe case of HAV in a Spanish-born patient who was incompletely vaccinated and recently im­migrated in Benin.

Observation

S. E., a 54-year-old woman was admit­ted in October 1^st, 2013 to a hospital in Cotonou for abdominal pain, vomit­ing, fatigue and low-grade fever last­ing for one week. Her history indicated there had been a laparoscopic cholecystectomy in Madrid in September 2013 for symp­tomatic cholecystolithiasis. She had no history of liver dis­ease or metabolic disease. She didn’t take any drug regularly. The Spanish-born woman who had been liv­ing in Benin for 10 months did not have a significant alcohol consumption. She had been vaccinated against hepatitis A(single dose) three years previously on an earlier trip to South America and had also been im­munised against hepatitis B. She lost the international vac­cination card and didn’t remember the name of the vaccine she took. The symp­toms had motivated an antimalarial treatment with the combination of artesunate 200 mg, sulfamethoxazole 500 mg and pyrimethamine 25 mg –  normal dose (one tablet per day for three days), without succes­s. Dur­ing the admis­sion in hospital, the patient was afebrile (after paracetamol), the general condition had altered (because of severe asthenia), her body mass index was 22.9 (weight 64 kg), umbilical perimeter was 81 cm, blood pres­sure 123/75 m­m Hg and heart rate 88/min. It was noted a conjunctival jaundice and tenderness of the epigastrium. The remainder of the examination was normal, there was no sign of hepatic encephalopathy. Laboratory tests (tab. 1) showed a negative thick blood, normal blood count as well as renal function tests, blood electrolytes and creatinine. We noted cytolysis (alanine aminotransferase (ALT) 95N (N –  times the upper limit of normal), aspartate aminotransferase (AST) 45N), cholestatic jaundice (total bilirubin 7.5N, conjugated bilirubin to 23N, alkaline phosphatase (ALP) 7N, γ-glutamyl transpeptidase (GGT) 10N). The rate of prothrombin was low at 47% and the C-reactive protein amounted to 32 mg/L. See­ing this picture of cholestatic jaundice in a patient shortly after cholecystectomy for stones, the first dia­gnostic hypothesis raised was residual stones in the bile ducts (cholelithiasis/choledocholithiasis). The second etiological hypothesis was acute viral hepatitis. Abdominal ultrasound showed a homogeneous hepatomeg­aly without bile duct dilatation of intra- and extrahepatic, and prothrombin time (TP) did not go back after the administration of vitamin K₁. Thus, the dia­gnosis was mov­ing more towards acute viral hepatitis. Serology for hepatitis B im­munisation showed anti-HBs antibodies to 411 mIU/mL, the serology for hepatitis C (HCV antibodies) was negative, im­munoglobulin M type of anti-HAV antibodies (IgM) was positive. The control in another laboratory confirmed acute HAV. The dia­gnosis of acute HAV with severe hepatic impairment was retained. The symp­tomatic treatment was favourable with slow normalisation of hepatic tests and TP. TP was normal after 10 days and bilirubin after three weeks. The normalisation of transaminases was slow (the control after three months showed normal AST but ALT to 3N, after five months transaminases were completely normalised), (tab. 1).

Discus­sion

This clinical case is interest­ing for several reasons:

1. The background –  the patient had undergone a recent cholecystectomy for symp­tomatic gal­lstones; and there­fore see­ing the picture of febrile jaundice and abdominal pain, the hypothesis of residual stones in the com­mon bile duct was primary evocated. But this as­sumption was quickly ruled out in the absence of bile duct dilatation from the abdominal ultrasound, despite not perform­ing any additional radiological examination such as magnetic resonance cholangiopancreatography. The positivity of IgM HAV led to the dia­gnosis of acute HAV.
2. The subject af­fected –  an incompletely HAV-vaccinated im­migrant. Although the HAV does not pose a health problem for people in endemic areas [4], it can be a source of morbidity in travel­lers from low-prevalence countries [5]. Vaccination is recom­mended for these subjects. The doses and vac-cination schema depend of the type of used vaccines and travel­ler’s age. For the isolated vaccines againt HAV (for example Havrix®), it is recom­mended the first dose of vaccination at least 15 days before departure to the endemic area with a booster 6– 12 months later [4,6]. Bet­ter is two full dose vaccination for adults before travel­­ing to endemic area. The scheme for this vaccination is a 1,440 IU dose in adults (720 IU in child­ren) at months 0 and 6 to 12 [4]. The vac­cine is ef­fective against HAV and protection is durable (12– 25 years) [6]. This vaccination scheme dif­fers in case of combined vaccines (for example boosters 2 months (M2) and 6–12 months (M6–M12) after the first dose in case of vaccines against HAV + HBV and another schema in case of vaccine against HAV + typhoid fever) [4,6]. Our patient had received only one dose of unknown vaccine dur­ing a previous trip, so anyway was incompletely protected. In the literature, cases have been reported in incompletely HAV-vaccinated patients [7] and also in ful­ly vaccinated patients reflect­ing the pos­sible failures of the vaccine [6]. It seems that the vac­cine ef­ficacy decreases with age. Wolters et al. had found that vaccination against HAV was only 65% ef­fective in subjects over 40 years of age [8]. They advocated, therefore, to verify vaccine protection in patients over 40 years of age before contact with the virus.
3. The last interest­ing point of this case is its clinical severity, shown by the presence of hepatocel­lular insuf­ficiency. Indeed, HAV is usual­ly a benign af­fection with 0.3– 1.5% mortality [6]. The adult patients usual­ly present with symp­tomatic forms. Morbidity and mortality increase with age [9]. In subjects aged 40 and over, mortality exceeds 2% [10]. The liver failure and mortality risk factors are age, co-infection with hepatitis B or C and sex (women be­ing at a higher risk) [6]. Our patient had two of these factors (female sex and age) as well as be­ing an incompletely vac­cinated im­migrant. Fortunately, evolution was spontaneously favourable.

Conclusion

This case demonstrates the importance and the neces­sity of full im­munisation against HAV in patients from Western countries who are travel­-­­­ing to highly endemic areas. It would be useful to check the ef­fectiveness of vaccination in subjects over 40 years of age before contact with the virus.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for bio­­­­medical papers.

Submitted: 14. 3. 2016

Accepted: 24. 5. 2016

Vincent Zoundjiekpon, MD

Digestive Disease Center

Vitkovice Hospital

Zaluzanskeho 1192/ 15

703 84 Ostrava

Czech Republic

vincent.zoundjiekpon@vtn.agel.cz