We describe a case of a 26-year-old Hispanic male, who presented (Day 1) to his primary care physician (PCP) office after he noticed progressively worsening yellowish discoloration of his eyes and skin for 10 days' duration. In addition, he had noticed dark urine for 2-3 weeks and pale colored stools for 5-7 days. He complained of nausea, generalized fatigue, and malaise but did not have any abdominal pain, fever, chills, diarrhea, or any skin rash. He was noted to have diffuse jaundice, hepatomegaly, and mild epigastric tenderness on examination. The laboratory evaluation revealed abnormalities in liver panel, with total bilirubin (TBili) of 12.2 mg/dL, alkaline phosphatase (AlkP) 272 IU/dL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of 2112 and 1055 IU/dL, respectively (Table 1). The complete blood count (CBC) and coagulation panel (INR) were normal at that time. He was admitted to our hospital where he underwent initial workup for painless jaundice. Upon initial evaluation by hepatology service, he informed us that he was originally from Puerto Rico and was living in the US for 17 years. He denied any history of significant illness as a child or any known history of liver disease in any family member. He denied any episodes of mental confusion and excessive sleepiness, as well as hematemesis, hematochezia, melena, or poor appetite. He also denied pruritus at any time and lower extremity edema or increased abdominal girth. He denied any recent sick contacts, animal exposure, or travel outside the US. He denied any history of incarceration, tattoos, or blood transfusions. He denied any history of tobacco use, illicit drug usage such as marijuana, cocaine, and heroin, or abuse of amphetamines. He reported drinking alcohol only on occasions and his last drink was approximately 7 months prior to this admission. However, he did report that he had been using over-the-counter anabolic steroids and a supplement from a vitamin store as a muscle-building high performance protein supplement (the ingredients are indicated in Table 3) on a daily basis for approximately 6 months. On examination, he appeared comfortable with diffuse jaundice and somewhat tender hepatomegaly. No clinical stigmata of advanced liver disease were identified on examination. The baseline serologic workup is shown in Table 2 which ruled out any infectious, autoimmune, or metabolic causes of his liver disease. The radiological workup with ultrasound, and a Magnetic Resonance Cholangiopancreatography did not reveal any biliary obstruction. He was suspected to have probable DILI with significant hyperbilirubinemia based on the negative etiologic workup. For further confirmation, he underwent a liver biopsy (Day 5) which revealed quite an impressive inflammatory process involving both portal areas and the lobules displaying also a pattern of sinusoidal lymphocytosis (Figure 1). The hepatocytic injury was identified and was more prominent in centrilobular (zone 3) location. Trichrome stain revealed only mild portal and periportal fibrosis and some perisinusoidal fibrosis especially in centrilobular location where the majority of the hepatocytic damage was identified along with mild collapse of the reticulin framework and likely was the result of hepatocytic dropout. Within the lobules, there was prominent "spotty necrosis," highlighted with the PAS positive, diastase resistant stain, revealing macrophages loaded with phagocytic debris. Iron stores were not increased and immunostain for adenovirus, cytomegalovirus (CMV), herpes virus, and hepatitis B surface antigen were also negative on the histologic tissue. Iron stain was negative and copper stain showed no increased copper deposition in the hepatocytes. Based on the above findings, he was started on a short course of oral prednisone and ursodiol (Day 8) as the treatment for severe AH with cholestasis. His laboratory tests showed gradual improvement in hepatitis and subsequently he was discharged to be followed up as outpatient. He was seen in the clinic for monitoring (Day 35) and reported over all symptomatic improvement and he had started back his job as a residential painter. His follow-up monitoring laboratory testing 6 weeks later showed continued improvement in AH (Figure 2) while he stayed on low dose ursodiol.
On his next set of monitoring laboratory testing (Day 142), new onset severe pancytopenia (Table 1) was identified which prompted urgent hospital admission for evaluation and management of his pancytopenia. All viral etiologies of acute pancytopenia were ruled out by serologic analysis. He did not have any family history of AA. Extensive hematological workup was performed and all other causes of primary SAA were ruled (negative anti-CD55 and anti-CD59 antibodies, negative urinary collections for lead and arsenic, and negative flow cytometry). Peripheral blood smear analysis revealed severe neutropenia and normocytic anemia with frequent target cells, consistent with clinical history of liver disease along with severe thrombocytopenia. He underwent a bone marrow biopsy and flow cytometry analysis which showed severe hypocellular bone marrow (less than 5%) with dyserythropoiesis (Figure 1). The cytogenetic study showed normal karyotype. Immunostain with CD3 and PAX5 stains showed no involvement of lymphoma. CD34, TdT, and CD117 stains confirmed no significant increase of blasts. D31 and Factor-VIII stains show virtual absence of megakaryocytes. In view of the patient's age, gender, and his presentation with initial AH, the diagnosis of HAAA was made. The patient did not have any full siblings and in view of the absence of matched HLA siblings, the decision was made to immediately initiate IST. He initially received thymoglobulin (ATG) along with methylprednisolone treatment for a total of 5 days. He received prophylactic antimicrobials, in addition to filgrastim daily and platelet transfusions as needed to support his peripheral cell count. He responded to the induction therapy with the improvement in cell counts and significant reduction in his liver enzymes. Later, he was kept on cyclosporine (Cys) and prednisone was tapered off. This resulted in stable cell counts and partial recovery of bone marrow (Day 160). IST was continued as cyclosporine monotherapy and further improvement in cell counts was seen (Figure 2). He continues on cyclosporine with complete recovery of HAAA (Table 1) after 3 years of initial presentation.