Primary Biliary Cholangitis (PBC) is a chronic cholestatic disease of the liver. Due to the permanent cholestasis, fibrosis and cirrhosis eventually occur. It is said to be a rare disease in black Africans. We reported a case of Anti-Mitochondrial Antibody (AMA) negative PBC in a forty-one-year-old woman who fulfilled two out of the three diagnostic criteria. This case was reported because a diagnosis of PBC is very rare in our environment especially, AMA negative PBC which is indeed the first to be reported in our environment. Although, access to newer methods of AMA assay were not possible in the light of the resource-limited environment we practice in.

      Primary biliary cholangitis (PBC) is a chronic cholestatic disease of the liver characterized by persistent and progressive cholestasis leading, eventually, to biliary fibrosis and cirrhosis [1]. It was previously known as primary biliary cirrhosis, but the name change was necessary to reflect the predominantly chronic inflammatory bile duct destructive changes seen until the latter stages when cirrhotic features will now mainly predominate [2]. The etiology is unknown although it has been presumed to be autoimmune in nature due to the presence of specific auto antibodies [3].

      The pathophysiologic basis involves a complex interaction between environmental factors, exposure to foreign compounds and molecular mimicry in genetically predisposed individuals. It is an uncommon disease with a prevalence of 1.91–40.2 per 100,000 inhabitants in the developed countries [4] and even less common in Africans and populations of African descent [5]. It is commoner in females than males and occurs mostly between the 4th and 6th decade of life. Higher occurrence in first-degree relatives of patients compared to the general population underlines a strong genetic predisposition [6].

      Chronic fatigue is usually the first and commonest presentation followed by puritus [7]. These two symptoms could be present for months to years while the liver function progressively deteriorate. Jaundice and features of cirrhosis are usually seen at the end stage of the disease.

      The diagnosis of PBC is made when 2 out of 3 of the following criteria are met: Elevated alkaline phosphatase greater or equal to 1.5 times the Upper Limit of Normal [ULN]), elevated serum Anti-Mitochondrial antibody (titers ≥1:40), and histological features consistent with PBC [8].

      PBC is seldom seen in black African population, hence the reason for reporting this case.

      A 41-year-old woman who was initially evaluated for obstructive jaundice at the surgical outpatient department. She was referred to the gastroenterology clinic by the surgeons due to non-response to cholestyramine and loratadine she was placed on, after abdominal imaging revealed no feature of surgical jaundice. She presented to the gastroenterology clinic on account of progressive fatigue noticed about 2years ago, pruritus and excessive darkening of her skin of over a month duration. She also had a right upper abdominal pain, yellowness of the eyes with associated passage of dark brown urine about a week prior to her clinic presentation. There was no history of autoimmune diseases in the patient and first-degree relatives. There was also no history suggestive of chronic decompensated liver disease or liver cirrhosis. Jaundice and Hepatomegaly were the only positive findings on physical examination. The liver had a smooth surface and span of 16cm. There were no other peripheral stigmatas of chronic liver disease. Her laboratory investigations showed the liver function assays as follows:

Table 1

      She was seronegative for Hepatitis B Surface Antigen (HBsAg), antibody to Hepatitis C Virus (Anti-HCV) and Human Immunodeficiency Virus (HIV). The packed cell volume was 33%, total white cell count was 5500/cmm and platelet count was 249,000/cmm. The prothrombin time was 14.1 seconds while the INR was 1. The serum cholesterol levels were elevated, the LDL-cholesterol was 3.61mmol/l (0 – 2.6mmol/l) while HDL-cholesterol was 1.73mmol/l (greater than 1.20mmol/l). Both the abdominal ultrasound scan and computed tomography scan revealed hepatomegaly with no coarsening of the echotexture nor distorted architecture, and no features suggestive of extrahepatic biliary obstruction. Markers of autoimmune liver disease, Anti-Nuclear Antibody (ANA) and Anti Mitochondrial Antibody (AMA) assays were also done, and they came out negative. At this point, based on the above investigations with no clear diagnosis, liver biopsy had to be done on this patient and the result of the histology showed an unaltered native liver architecture with preserved vascular relationships. The portal area was expanded by fibrosis and infiltrated by lymphocytes bridging the limiting plates. Many portal areas showed bile duct proliferation and many ducts show damaged epithelial lining cells and disrupted basement membranes in keeping with Ludwig stage III.

      With the elevated level of alkaline phosphatase above two times upper limit of normal on three occasions and the liver histological feature almost diagnostic of PBC, a diagnosis of PBC was made.

      She was subsequently placed on Ursodeoxycholic acid at a dose of 15mg/kg but defaulted follow-up visits. She was interacted with through teleconsultation, and she attested to resolution of her symptoms as the main reason for her clinic default, although she claimed to have continued the medication during this period. Biochemical and/or histological improvements, if any, were not verifiable because of the default.

      Primary biliary cholangitis is an uncommon liver disease especially in Africans [5] and there has been no previous study about the prevalence in Nigeria. Search through Nigerian literature showed only one ever reported case of PBC in south-southern Nigeria by Agbo et al [9]. They described a patient that satisfied all the 3 criteria for diagnosing PBC. Even rarer, accounting for only about 5% of patients, are those with AMA negative type of disease [10] such as in our index patient. Therefore, a high index of suspicion is required to make such diagnosis in this environment.

      We had a typical female patient in her fifth decade with the classic symptoms of fatigue, pruritus, and hyperpigmentation. Diagnosis of PBC in this case was made based on the clinical features and two of the three laboratory criteria including the histological features of PBC.

      Her clinical presentation was like the case described earlier in Nigeria and typical of what is known of the symptomatology of PBC. There was also concordance between her symptoms and the advanced liver histologic features (fibrosis) she had. This is in keeping with previous findings that non-Caucasians have more severe disease based on clinical and laboratory criteria [11] as was the case in our patient.

      Anti-mitochondrial antibody is present in about 80% of PBC patients using the indirect immunofluorescence assay, the rest of the patients are negative and are simply labelled as having autoimmune cholangitis, now known as AMA negative PBC [12]. About 30%-50% of AMA negative PBC tests positive to ANA also using the indirect immunofluorescence assay [13]. Our patient tested negative to both AMA and ANA which made diagnosis a little difficult to arrive at. However, she fulfilled the other two components of the diagnostic criteria. To our knowledge, this is the first case of AMA negative PBC to be reported in Nigeria. The limitation experienced with respect to access to current and more advanced AMA and ANA assay methods meant that the patient could actually be AMA positive and/or ANA positive if the assay was done by some of these newer more sensitive methods. Immunoblotting and enzyme-linked immunosorbent assay for AMA are more specific than indirect immunofluorescence assay. Up to 95% of PBC patients becomes AMA positive when these newer methods are used to complement indirect immunofluorescence assay [10]. PBC specific ANA such as, anti-sp100, anti-gp120, antikelch-like 12, antihexokinase, if done, could have also helped in strengthening diagnosis of PBC in this patient.

      In conclusion, primary biliary cholangitis has been reported in all races and ethnicities, it is likely underdiagnosed in our resource-challenged setting as routine autoimmune markers are almost not readily accessible in our practice. A search for an autoimmune process should be considered after excluding the common causes of cholestasis in our environment.

      The authors certify that they have obtained all appropriate informed patient consent. In the form, the patient gave her consent for the clinical information and the included image to be reported in the journal. The patient understands that her name and initials will not be published, and due effort will be made to conceal her identity. However, anonymity cannot be guaranteed.

      The authors declare no conflicts of interest.