Autoimmune Hepatitis Disguised as Iron Overload Syndrome: Diagnostic Dilemma in a Nigerian Man

Abstract

Autoimmune hepatitis (AIH) is an extremely rare cause of chronic liver disease (CLD) in sub-Saharan Africa—there have only been 3 reported cases of AIH in Nigeria, a country of about 200 million people. We report the first case of AIH in a male patient in Nigeria and highlight its unusual presentation. A 41-year-old man with jaundice and malaise for 3 months was referred for evaluation after investigations revealed deranged liver enzymes and a cirrhotic liver. Laboratory evaluation revealed high serum immunoglobulin G, but there was also marked elevation of serum ferritin and transferrin saturation, resulting in a diagnostic dilemma between AIH and an iron overload condition such as hemochromatosis. A liver biopsy was crucial in providing a definitive diagnosis of AIH. Despite its rarity, clinicians should maintain a high index of suspicion for AIH in sub-Saharan Africa and should proceed to a liver biopsy when the cause of CLD is unclear.

Introduction

Chronic liver disease (CLD) is a major cause of morbidity and death in sub-Saharan Africa, with viral hepatitis being the predominant cause of CLD in the region. ¹ In Nigeria, about 20 million people are chronically infected with hepatitis B and C viruses, with a recent national household survey reporting a prevalence of 7.63% and 1.73%, respectively. ² Autoimmune hepatitis (AIH) is a rare long-term neuroinflammatory disease of the liver and has scarcely been described in Nigeria, a country with an estimated 200 million people. ³ There have only been 3 reported cases of AIH in Nigeria and these were all in women, mirroring the female predominance of AIH observed globally.^4-6 Here we report the first case of AIH in a male patient in Nigeria whose presentation mimicked hemochromatosis and highlight its management challenges.

Case Presentation

A 41-year-old Nigerian man with no significant past medical history presented with chief complaints of jaundice, nausea, fatigue, and unintentional weight loss over 2 months. He reported rare alcohol use and denied illicit drug use or a family history of liver disease. He had no history of use of herbal medications and did not have a history of obesity. Physical examination was unremarkable except for scleral icterus. Laboratory evaluation revealed elevated aspartate transaminase 315 U/L, alanine transaminase 358 U/L, alkaline phosphatase 144 U/L, total bilirubin 5.6 mg/dL, and direct bilirubin 2.9 mg/dL. Viral hepatitis panel was negative. Abdominal ultrasound and computed tomography revealed findings consistent with liver cirrhosis without any evidence of ascites or a focal liver lesion. Ceruloplasmin, alpha 1 antitrypsin, and alpha-fetoprotein were within normal range. Antismooth muscle (ASMA), antimitochondrial, antiactin, and liver-kidney microsomal antibodies (anti-LKM) were negative, but serum immunoglobulin G (IgG) was notably elevated (19 g/dL) and this raised concern for AIH as the cause of CLD. Iron profile was obtained, and this caused a diagnostic challenge as it revealed markedly elevated serum ferritin of 1349 ng/mL and transferrin saturation of 56%, leading to suspicion of an iron overload syndrome as the cause of CLD. He had no history of receiving blood products or iron supplementation, and he denied a family history of hemochromatosis. Hemoglobin A1c was within normal limits, and he denied long-term joint pain, erectile dysfunction, or symptoms of heart failure. Given the diagnostic dilemma between AIH and hemochromatosis—as suggested by high serum IgG and concomitant elevation of ferritin and transferrin saturation, respectively, a liver biopsy was performed for definitive diagnosis. Histopathologic evaluation revealed interface hepatitis with fibrosis, moderate inflammation of the portal tracts, mild steatosis, and focal lobular inflammation, consistent with AIH (Figure 1). Perls’ Prussian blue staining was negative, effectively excluding iron overload as the cause of CLD (Figure 2). The patient was started on oral prednisolone for the treatment of AIH, and there was an improvement in clinical and laboratory parameters on follow-up.

Figure 1.

Liver biopsy images showing interface hepatitis: portal and periportal infiltrate with plasma cells and lymphocytes (letter A).

Figure 2.

Negative Perl’s Prussian blue stain with no iron deposits identified (letter B).

Discussion

Autoimmune hepatitis is a rare disease described first by Waldenstrom in 1950. ⁷ This disorder, which was termed lupoid hepatitis because of its association with autoimmune syndromes, is significantly more common in women and was renamed in 1965 by Mackay et al as AIH. ⁸ The most common type of AIH is type 1 which can occur at any age, while type 2 is more common in children and young adults. The pathophysiology of AIH remains poorly understood but genetic susceptibility is thought to be a crucial factor, in addition to the interactions between a tolerant liver, dysregulated immunological mechanisms, and an environmental trigger. ⁹ While the worldwide incidence of AIH is around 1 per 100,000, it is thought to be extremely rare in sub-Saharan Africa due to the lack of medical facilities leading to underdiagnoses; only 3 cases have been reported in Nigeria. ¹⁰ This is the first report of AIH in a male patient in Nigeria and the fourth case overall. More importantly, it is the third report of AIH in the literature with this unusual presentation mimicking iron overload syndrome.^11,12 Owing to its fluctuating nature, the presentation of AIH can vary from asymptomatic disease to manifestation with features of decompensated cirrhosis, like the index patient that presented with jaundice. In addition to clinical features and abnormal liver enzymes, elevated serum IgG levels and autoantibodies, such as ASMA, ANA, and anti-LKM, support a diagnosis of AIH. The index patient had high serum IgG, but autoantibodies were not elevated. Mack et al reported that about 20% of AIH cases are negative for ANA, anti-LKM, and SMA. ¹³ Ferritin, an acute phase reactant that is elevated in a proportion of patients with CLD, was also elevated in the patient. Surprisingly, he also had high transferrin saturation of 56%, leading to a diagnostic dilemma between AIH and an iron overload condition. Hereditary hemochromatosis, a genetic disorder of iron metabolism with an estimated prevalence of 0.05% to 0.37%, is characteristically associated with serum transferrin saturation of greater than 45% to 50% and leads to CLD if left untreated. ¹¹ Notably, our patient did not have any clinical features consistent with hemochromatosis. A liver biopsy was vital in arriving at the correct diagnosis in this case and is the gold standard for diagnosing AIH while allowing for the assessment of liver fibrosis. Pathological findings that confirm AIH include interface hepatitis, regenerative rosettes, and plasma cell predominance in the portal inflammatory infiltrate. ¹² While our patient had classic histopathologic findings supportive of the diagnosis of AIH, the absence of iron following special staining effectively ruled out hemochromatosis, and there was no need to pursue HFE genetic testing. This is the third description in the literature of a patient with AIH presenting with high transferrin saturation, and the underlying reason for this phenomenon is unclear. The subjects in the first two reports were older women in North America who, like our patient, had positive antibodies: anti-SMA was positive in one and the other had a low ANA titer.^11,12 To the best of our knowledge, this is the first report of AIH in a Nigerian male and our case highlights an unusual presentation for this rare condition in sub-Saharan Africa. Clinicians should maintain a high index of suspicion for AIH in patients presenting with liver disease, even in settings where it has an extremely low incidence, and should be aware of this unusual presentation. Liver biopsy should be pursued early to guide diagnosis when there is uncertainty regarding the cause of CLD.