For a patient with suspected autoimmune hepatitis, should steroids or a liver biopsy be done first?

Liver Biopsy Should Be Performed First Before Starting Steroids

In patients with suspected autoimmune hepatitis, liver biopsy should be performed before initiating corticosteroid therapy, as histological confirmation is considered a prerequisite for diagnosis and essential for guiding treatment decisions. 1, 2

Why Biopsy Must Come First

Diagnostic Necessity

• Liver biopsy is mandatory for establishing the initial diagnosis of AIH because the disease lacks a signature diagnostic marker, and histology provides critical diagnostic and prognostic information that cannot be obtained through serologic testing alone. 1, 2
• The general consensus across major hepatology societies is that AIH cannot be diagnosed without compatible histological findings, considering the need for differential diagnosis from other conditions. 1
• Approximately 10-25% of AIH patients present with normal IgG levels, and autoantibodies may be absent in 20% of cases, making histological confirmation even more critical. 1, 3

Differential Diagnosis Requirements

• Liver biopsy is essential for distinguishing AIH from other conditions that can mimic it clinically, including:
  • Drug-induced liver injury (DILI), which accounts for approximately 9% of patients initially suspected to have AIH 3
  • Viral hepatitis (particularly hepatitis C) 1, 4
  • Wilson's disease 1
  • Non-alcoholic steatohepatitis 1
• The histological features help differentiate these conditions when clinical and serological findings overlap. 5, 4

The Exception: Acute Liver Failure

When Steroids May Be Started Simultaneously

• In acute liver failure (ALF) suspected to be AIH, corticosteroids (prednisone 40-60 mg/day) should be initiated while simultaneously attempting to obtain liver biopsy. 1
• Even in this urgent scenario, biopsy should still be strongly pursued via transjugular approach if severe coagulopathy is present, as it can establish the diagnosis when autoantibodies may be absent. 1, 2
• Patients should be placed on the transplant list even while corticosteroids are being administered, as some patients require transplantation despite steroid therapy. 1

Histological Findings in ALF-AIH

• In acute presentations, liver biopsy may reveal severe hepatic necrosis accompanied by interface hepatitis, plasma cell infiltration, and hepatocyte rosettes—findings that support AIH diagnosis. 1
• However, acute-onset AIH may present with centrilobular necrosis, which can also be seen in drug-induced liver injury, making careful clinicopathological correlation essential. 5

Safe Biopsy Techniques When Coagulopathy Exists

Overcoming Contraindications

• The only acceptable scenario to defer pre-treatment biopsy is uncorrectable severe coagulopathy where transjugular or laparoscopic approaches are unavailable. 2
• Transjugular liver biopsy should be used when severe coagulopathy is present, allowing safe tissue acquisition even with significant bleeding risk. 2
• Mini-laparoscopy with visual control is an alternative safe approach even in advanced coagulopathy. 2

The Steroid Trial Approach: A Last Resort

When Empiric Treatment Is Considered

• A therapeutic trial with steroids (starting at 40-60 mg/day prednisone) may be considered only in exceptional circumstances where biopsy is truly impossible and clinical suspicion for AIH remains very high. 1, 6
• If using a steroid trial approach, quick tapering of steroids is recommended—if the disease responds well but recurs after tapering, the diagnosis of AIH is confirmed. 6
• This approach should be reserved for atypical cases where diagnostic scores are insufficient and biopsy is genuinely contraindicated. 6

Critical Histological Features That Guide Treatment

Key Diagnostic Findings

• Interface hepatitis (present in 100% of untreated cases) 7, 4
• Plasma cell clusters (present in 88% of cases) 7, 4
• Hepatocyte rosettes 1
• Portal and periportal inflammation with lymphoplasmacytic infiltrates 2, 7
• Emperipolesis (56% of cases) 7

Prognostic Information

• Liver biopsy assesses disease severity, including the presence of bridging necrosis or multilobular necrosis, which are absolute indications for treatment. 8
• Histology evaluates the degree of fibrosis, which has prognostic implications and can show substantial regression with sustained treatment response. 8
• Examination of liver tissue remains the best method of evaluating both treatment response and need for treatment in patients who have little biochemical activity. 8

Common Pitfalls to Avoid

• Never rely solely on serological markers for AIH diagnosis—histological confirmation is mandatory. 2, 9
• Do not assume that elevated transaminases and positive autoantibodies are sufficient for diagnosis without biopsy. 1, 9
• Avoid missing the diagnosis of drug-induced liver injury by failing to obtain histology, as DILI can present identically to AIH clinically. 3, 5
• Do not overlook the possibility of AIH in patients with normal IgG levels or negative autoantibodies—biopsy is even more critical in these seronegative cases. 1, 3