An atypical presentation of autoimmune hepatitis with delayed menarche in a Nigerian adolescent: a case report

Abstract

Background

Autoimmune hepatitis is a chronic liver disease marked by immune-mediated inflammation, necrosis, and the potential to progress to cirrhosis if not treated. This case report presents a rare and atypical presentation of autoimmune hepatitis in a Nigerian adolescent girl, highlighting diagnostic challenges in resource-limited settings. The case is unique owing to the absence of jaundice, a common symptom of liver dysfunction, and features such as delayed menarche and bilateral leg swelling.

Case presentation

The patient was a 16-year-old Black female patient of Igbo ethnicity from Nigeria, who presented with a 6-month history of bilateral leg swelling and delayed menarche. She had no history of jaundice and abdominal pain, and she had no significant past medical history. She was initially misdiagnosed, delaying appropriate management. Following a comprehensive diagnostic workup, including liver function tests, imaging, and autoantibody testing, which were positive for antinuclear and antismooth muscle antibodies, she was correctly diagnosed with type 1 autoimmune hepatitis. Treatment was initiated with corticosteroids (prednisolone) and azathioprine, which resulted in clinical improvement. However, her serum albumin levels remained low as a result of the preexisting cirrhosis.

Conclusions

This case highlights the diagnostic challenges of autoimmune hepatitis in adolescents, particularly in regions where infectious liver diseases are more commonly suspected. It emphasizes the need for increased awareness and better diagnostic resources to improve early detection and management of autoimmune hepatitis in sub-Saharan Africa. Early intervention with immunosuppressive therapy is essential, even in the absence of classic liver-related symptoms, to prevent progression to advanced liver disease.

Background

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. It is characterized by continuing hepatocellular inflammation, necrosis, and the potential to progress to cirrhosis if left untreated [1]. It has a universal distribution, affecting individuals of all ages and genders, with a global prevalence of 17.44 (95% confidence intervals (CI): 12.01–22.87) per 100,000 persons [2]. The condition has been reported to be more prevalent in females, the elderly, and white individuals compared with males, younger age groups, and other ethnicities. In addition, patients with AIH are more likely to have coexisting autoimmune conditions such as Sjögren’s syndrome, systemic lupus erythematosus, and autoimmune thyroiditis, among others [3]. Unfortunately, there is limited reporting of AIH in Nigeria and the sub-African region.

The diagnosis of AIH requires the exclusion of other chronic liver diseases such as Wilson’s disease, chronic viral hepatitis, and metabolic-associated steatotic liver disease (MASLD), along with the establishment of the presence of the characteristic set of autoantibodies, elevated immunoglobulin (Ig)G concentrations, and histological demonstration of periportal necrosis and interface hepatitis [4]. The disease may present asymptomatically, with nonspecific symptoms such as fatigue and amenorrhea, or with an acute onset of jaundice, and it can also have overlapping features with other liver diseases [5]. The preferred treatment for AIH involves corticosteroids such as prednisolone combined with azathioprine, while second-line treatments include alternative immunosuppressants like mycophenolate mofetil, calcineurin inhibitors, budesonide, and 6-mercaptopurine (6-MP). In cases of treatment failure, liver transplantation may be necessary [6]. Although the condition is relatively well-documented in Western populations, it is rarely reported in sub-Saharan Africa. This case report adds to the limited body of literature on AIH in African and emphasizes the importance of early diagnosis and treatment to prevent further liver damage in similar cases.

Case presentation

A 16-year-old Black female secondary-school student of Igbo ethnicity from Nigeria presented at the Gynecology Clinic of Enugu State University Teaching Hospital (ESUTH) Parklane with a 6-month history of bilateral leg swelling and delayed menarche. She was referred to the gastroenterology unit of the hospital following abnormal liver function test results. The patient had no history of jaundice, abdominal pain, shortness of breath, or gastrointestinal symptoms. There was no significant past medical history, and she had no family history of liver disease.

On physical examination, the patient had grade 2 bilateral pitting edema, but was otherwise in no distress. Abdominal examination revealed a liver span of 10 cm with no palpable spleen or demonstrable ascites. Cardiovascular and respiratory examinations were unremarkable and neurologic examination showed no signs of encephalopathy.

Laboratory tests revealed elevated liver enzymes, hypokalemia, and abnormal hormone profiles. Serum proteins revealed markedly reduced albumin and elevated globulin, and the electrophoresis pattern showed hypergammaglobulinemia with beta-gamma bridging and hypoalbuminemia, suggesting the presence of liver cirrhosis (Table 1). An abdominal ultrasound showed coarse echotexture of the liver with reduced periportal markings consistent with cirrhosis, and an echogenic mass in the gallbladder casting posterior acoustic shadow in keeping with cholelithiasis. Esophagogastroduodenoscopy (EGD) revealed Grade 2 esophageal varices, while further investigations, including positive antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) tests, confirmed the diagnosis of type 1 autoimmune hepatitis. The international autoimmune hepatitis pretreatment score (IAHPS) was 16, indicating probable AIH.

Table 1 Baseline investigation results showing liver function test, hormone profile, electrolytes and other tests alongside their reference intervals

Differential diagnosis

The differential diagnosis of AIH involves ruling out several conditions that can present with similar clinical and biochemical features. One of the primary considerations was viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), which are the leading causes of chronic liver disease and cirrhosis worldwide, and particularly in Nigeria [7, 8]. In this case, serologic testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) was negative, effectively ruling out viral hepatitis as the cause of liver disease.

Wilson’s disease, a genetic disorder of copper metabolism, was also considered due to the patient’s young age and presentation with cirrhosis. However, the absence of Kayser–Fleischer rings and any neurological symptoms made Wilson’s disease unlikely [9]. MASLD, which is commonly associated with metabolic syndrome and obesity, was considered, but was less probable owing to the absence of risk factors such as obesity or diabetes and the characteristic ultrasound features of steatosis [10].

Primary biliary cholangitis (PBC) was another possibility given its autoimmune nature and potential to cause cirrhosis. However, negative testing for AMA and the absence of typical cholestatic liver function tests made PBC unlikely [11]. Drug-induced liver injury (DILI), which can mimic AIH [12], was ruled out due to the lack of history of exposure to hepatotoxic drugs or herbal remedies.

Another consideration was overlap syndromes where AIH coexists with conditions such as PBC or primary sclerosing cholangitis (PSC). However, imaging showed no bile duct involvement, and antibody tests for these conditions were negative [13]. Thus, after ruling out these differential diagnoses, the presence of positive autoantibodies, elevated liver enzymes, serum protein findings, and the absence of viral or metabolic causes supported the diagnosis of autoimmune hepatitis [4], which was further confirmed by the patient’s response to immunosuppressive therapy.

Finally, the diagnosis of type 1 AIH in this patient was supported by several factors. The patient presented with elevated levels of ANA and ASMA, which are hallmark serological markers of type 1 AIH. Although microsomal type 1 (anti-LKM1) antibodies were not tested to rule out type 2 AIH, the patient’s age at presentation was consistent with the typical presentation of type 1 AIH, which often occurs during adolescence or adulthood. This diagnosis was further reinforced by the patient’s remarkable response to treatment, as opposed to type 2 AIH, which is often more resistant to standard treatments such as corticosteroids [4].

Treatment and outcome

The patient was initially treated with prednisolone 30 mg daily and azathioprine 100 mg daily, with other medications including spironolactone 50 mg daily, furosemide 40 mg daily, Astymin once daily, and Livolin Forte every 12 hours. A total of 2 weeks into treatment, the patient reported weight gain, and prednisolone was reduced to 10 mg daily. Her liver function tests and symptoms improved significantly with continued treatment over the next 2 weeks and prednisolone was further reduced to 5 mg daily while the patient was maintained on azathioprine and other supportive medications.

On follow-up in the sixth week of management, repeat liver function tests showed improved bilirubin levels, normalized alkaline phosphatase, and reduced transaminases (Table 2). Serum proteins also showed improvement, with albumin levels returning closer to normal. However, liver biopsy and serum electrophoresis assays were not performed.

Table 2 Follow-up investigation results showing liver function and serum protein tests alongside their reference intervals

Discussion

Type 1 AIH is characterized by a multifactorial pathogenesis, involving both genetic predisposition and environmental triggers that disrupt immune tolerance to liver antigens. A hallmark of the disease is the presence of autoantibodies, most notably ANA and ASMA, indicating immune dysregulation [4]. In this process, autoreactive CD4⁺ T cells are believed to target hepatocytes, triggering chronic inflammation, necrosis, and potential progression to fibrosis [14]. Genetic susceptibility is closely linked to human leukocyte antigen (HLA) class II alleles, particularly HLA-DR3 and HLA-DR4, which are found in a significant proportion of AIH patients, suggesting impaired immune regulation and tolerance to liver-specific antigens. The association of these alleles points to defective antigen presentation and immune activation as central to the pathogenesis of AIH [15, 16]. Additionally, the disease exhibits a marked female predominance, with estrogen being proposed as a modulating factor in the immune response. Although various mechanisms have been proposed, its exact role remains unclear [3, 17, 18]. Environmental factors, including viral infections and certain medications, can serve as potential triggers in genetically predisposed individuals, initiating or exacerbating the autoimmune process [14,15,16]. These factors converge to cause persistent liver inflammation, which, if untreated, may lead to cirrhosis and liver failure.

The paucity of reported AIH cases in sub-Saharan Africa may be due to underdiagnosis, limited awareness, and lack of diagnostic resources, rather than a true lower incidence. Many healthcare providers in the region focus on infectious causes of liver disease, such as viral hepatitis, owing to their higher prevalence [7, 8]. This can delay the recognition and treatment of autoimmune liver diseases like AIH, as was seen in this case where the patient was initially misdiagnosed with other conditions before being referred to the gastroenterology unit.

This patient presented with nonspecific symptoms of liver disease, including bilateral leg swelling and delayed menarche, without classic signs such as jaundice or ascites. The absence of jaundice, a common early sign of liver dysfunction, made the initial diagnosis more challenging. This could be attributed to the predominance of noncholestatic processes, where the liver’s ability to excrete bilirubin remains relatively intact despite significant parenchymal damage, as seen in conditions like compensated cirrhosis [19]. The patient’s delayed menarche, a rare feature of AIH, was likely due to chronic liver disease disrupting hormonal balance, particularly estrogen levels, as suggested by elevated estradiol and undetectable follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels [20], prompting her initial referral to the gynecologist. Her eventual diagnosis was based on clinical features, liver function tests, abnormal serum proteins, and positive autoantibodies, and it was supported by the IAHPS System, which classified her as having probable AIH.

In resource-limited settings such as Nigeria, infectious liver diseases, particularly viral hepatitis, are more prevalent and are often the primary focus of diagnostic evaluation. This can delay the recognition of AIH, especially in patients who present with advanced liver disease and complications like cirrhosis. The diagnostic process was further complicated by the lack of access to specialized diagnostic approaches which are often necessary for confirming AIH. Consequently, underdiagnosis or misdiagnosis can lead to delayed treatment and increased risk of irreversible liver damage. This case emphasizes the need for a high index of clinical suspicion and improved diagnostic capacity to enable earlier identification and treatment of AIH, which is critical for preventing disease progression and improving patient outcomes.

Corticosteroids are the mainstay of treatment in AIH [5], with their anti-inflammatory and immunosuppressive effects helping to reduce liver inflammation and prevent disease progression. Azathioprine, a purine analog, helps maintain remission and allows for a reduction in steroid dosage, thus minimizing long-term steroid side effects such as bone loss, diabetes, and hypertension [21, 22]. This patient responded well to treatment, with improvements in both her clinical symptoms and biochemical markers. However, despite the biochemical response and resolution of hepatic inflammation, her serum albumin remained low, which was expected given the preexisting cirrhosis. This further highlights the importance of early diagnosis and intervention in AIH to prevent progression to advanced liver disease.

The prognosis of type 1 AIH largely depends on early diagnosis and the initiation of appropriate therapy. In untreated cases, the disease progresses to cirrhosis in over 40% of patients, with an increased risk of liver failure and death. However, with prompt treatment, the prognosis is generally favorable, with most patients achieving remission and long-term survival [4, 23]. In this case, the patient had already developed cirrhosis at the time of diagnosis, which complicates her long-term prognosis. Patients with AIH-related cirrhosis are at risk for decompensated liver disease, hepatocellular carcinoma, and the need for liver transplantation [1, 4]. Regular monitoring of liver function, imaging, and screening for complications such as varices and hepatocellular carcinoma will be critical in her long-term management.

Lessons learned and implications for clinical practice

• Autoimmune hepatitis (AIH) should be ruled out in any young patient with unexplained liver disease, even in the absence of classic symptoms like jaundice. This necessitates high clinical suspicion and awareness.

• Access to autoantibody testing and liver biopsies is crucial for accurate diagnosis, and improving access to these tools in resource-limited settings is essential for timely identification of AIH.

• Early initiation of immunosuppressive therapy, such as corticosteroids and azathioprine, is critical for preventing disease progression and improving long-term outcomes.

• The rarity of AIH in African adolescents underscores the need for greater clinician awareness, with training and education focused on recognizing and managing autoimmune liver diseases.

• Further research is needed to understand AIH’s epidemiology in Africa and to develop strategies for enhancing diagnostic capabilities and treatment access, with public health initiatives aimed at increasing provider awareness and training.

Conclusion

Autoimmune hepatitis (AIH) is a rare but significant cause of liver disease in adolescents, particularly in sub-Saharan Africa, where it is often underdiagnosed. This case report shows that AIH can present with advanced liver disease even in the absence of classic symptoms, emphasizing the importance of early recognition and intervention. Improving awareness and access to diagnostic and therapeutic resources is vital for enhancing the management and outcomes of patients with AIH in resource-limited settings.