An Acute Severe Dilemma

Tom Couri

Case

A 61 year old male with a history of recently diagnosed autoimmune hepatitis presents with fatigue and generalized weakness for 1.5 weeks. He denies fevers, chills, abdominal pain or swelling, and confusion. On exam, he has scleral icterus but no ascites or asterixis. Labs are notable for a total bilirubin of 8.1, AST 1,412, ALT 1020, and INR of 1.5.

What is best next step in management?

Correct Answer:

Start 1mg/kg per day of prednisolone

The correct answer is B, start 1 mg/kg per day of prednisolone. This patient is presenting with an  acute severe autoimmune hepatitis (AIH) flare. This is the most likely diagnosis given his established history of AIH, elevated liver enzymes, and lack of signs and symptoms of acute liver failure. The recommended treatment for an acute severe AIH flare is 0.5-1mg/kg of prednisolone per day, with close observation over the next several days to monitor for a response to the treatment. If symptoms and labs improve, the steroids are eventually tapered and azathioprine is typically added; if these parameters don’t improve, a liver transplant evaluation is initiated. Azathioprine and mycophenolate mofetil are not first line treatments for an acute severe AIH flare.

Autoimmune hepatitis definitions

Taken from: Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? Liver Transplantation 2019.

Establishing the Diagnosis of Acute Severe Autoimmune Hepatitis

Making a diagnosis of acute severe autoimmune hepatitis (AS-AIH) is critical to providing safe, rapid treatment. Because the treatment of choice is corticosteroids, which carry a risk of harmful side effects including infection, other conditions must be ruled out. Viral hepatitis can present similarly to AS-AIH, thus testing for hepatitis A, B, C, along with herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, and parvovirus should be carried out. In addition, hepatitis E virus testing, which is a rare mimicker of AS-AIH, must be excluded. Drug-induced liver injury, autoimmune cholangiopathy, Wilson's disease, and Budd-Chiari syndrome are other liver diseases that can present similarly. Along with excluding these other conditions, the diagnosis of AIH--if not already definitively diagnosed--can be secured with positive serologic markers such as anti-nuclear antibodies, anti-smooth muscle antibodies, or anti-liver kidney microsome antibodies, and a liver biopsy, which is the gold standard of diagnosis. Interface hepatitis, hepatocyte rosettes, and emperipolesis (one cell telescoping into another) are common histologic findings in AIH (Figure 2). Ultimately, there are gold standard criteria that incorporate labs, serology, and histology to diagnose AIH definitively.

Back to the case:

The patient was admitted to the hospital and underwent further testing. An abdominal ultrasound with doppler was negative for any thromboses, and viral hepatitis testing was negative. A thorough review of the patient's medications was negative for any potential hepatotoxic medications.

Figure 1 - Spectrum of presentation for AIH.

Taken from: Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? Liver Transplantation 2019.

Figure 2 - Autoimmune hepatitis histology. A: interface hepatitis; B: interface hepatitis, magnified; C: necro-inflammatory lobular hepatitis; D: emperipolesis (arrow shows intracytoplasmic lymphocytes).

Taken from: Approach to the Patient with Acute Severe Autoimmune Hepatitis. JHEP Rep 2020.

Inpatient Management of Acute Severe AIH

The first line therapy for AS-AIH is corticosteroids. Response rates vary, ranging from 20%-100%. The recommended medication and dose is prednisolone 0.5-1mg/kg/day. Hospitalization is recommended for close monitoring not only for biochemical response but also for lack of clinical improvement and potential progression to acute liver failure. MELD labs once or twice daily should be measured, and if there is biochemical and clinical improvement by seven days, the steroids should be tapered and azathioprine can be considered as an adjunctive agent. The most crucial element of AS-AIH management is determining whether urgent liver transplant evaluation should be initiated. The development of hepatic encephalopathy or lack of biochemical response or improvement after one to two weeks of steroid therapy requires a consideration for liver transplant. Of note, statistically significant increases in sepsis have not been shown for AIH patients treated with steroids.

Figure 3 - Management algorithm for acute severe AIH.

Taken from: Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? Liver Transplantation 2019.

Back to the case:

The patient was started on 1mg/kg/day of prednisolone. His LFTs and INR improved over the next 3 days, with his total bilirubin decreasing from 8.1 to 2.8, AST and ALT from 1,412 and 1,020 to 209 and 213, respectively, and INR from 1.5 to 1.2. He did not develop encephalopathy, and his fatigue and weakness improved. He was discharged with prednisone 60mg once daily, with a plan to taper the steroids weekly and add on azathioprine as an adjunctive agent in two weeks.

Take Home Points:

  • Acute severe autoimmune hepatitis (AS-AIH) is an acute flare of autoimmune hepatitis manifesting an INR of at least 1.5 in the absence of chronic liver disease.
  • Viral hepatitis, drug induced liver injury, and vascular liver disorders should be ruled out in the setting of suspected AS-AIH.
  • 0.5-1mg/kg/day of prednisolone is the first line treatment for AS-AIH.
  • If there is a lack of biochemical improvement after one to two weeks of steroid therapy, or the patient develops hepatic encephalopathy, urgent liver transplant evaluation should be initiated.

Related Content