Comparison of Clinical Features and Liver Histology in Liver Failure Caused by Autoimmune Hepatitis with Different Prognosis

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Comparison of Clinical Features and Liver Histology in Liver Failure Caused by Autoimmune Hepatitis with Different Prognosis

Autoimmune hepatitis (AIH) is a liver parenchymal inflammation mediated by autoimmune responses targeting hepatocytes. While traditionally recognized as a chronic condition, recent evidence indicates that AIH can manifest as acute hepatitis or even progress to liver failure (AIH-LF), a life-threatening complication with a 90-day mortality rate exceeding 40%. Understanding the factors influencing AIH-LF prognosis is critical for timely intervention and improving patient outcomes. This study compared clinical characteristics, laboratory findings, and histopathological features of AIH-LF patients with divergent prognoses to identify predictors of recovery or deterioration.

Study Design and Patient Stratification

The retrospective analysis included 53 AIH-LF patients treated at a single center between 2009 and 2019. AIH diagnosis was confirmed using the 1999 International Autoimmune Hepatitis Group criteria or simplified AIH scoring system. Liver failure (LF) was defined per Chinese guidelines. Patients were stratified into two groups: the improvement (I) group (n=26), characterized by clinical cure, amelioration without transplantation within six months, and the deterioration (D) group (n=27), comprising patients with worsening conditions, death from LF, or requiring transplantation. Clinical data, laboratory parameters, autoantibody profiles, and liver histology were analyzed.

Demographic and Clinical Characteristics

The cohort comprised 4 males and 49 females (mean age: 48.7 ± 14.7 years). No significant age or sex differences existed between groups. However, key differences emerged in disease history and LF subtypes:

  • Disease Duration: 59.2% (16/27) of D-group patients had an AIH diagnosis >6 months prior to LF onset, compared to 34.6% (9/26) in the I-group (P=0.039). The interval from AIH diagnosis to LF was markedly longer in the D-group (26.5 vs. 13.0 months; P=0.009).
  • LF Classification: The I-group exhibited a higher prevalence of subacute LF (SALF) (46.2% vs. 14.8%; P=0.004), whereas acute-on-chronic LF (ACLF) or subacute ACLF (SACLF) predominated in the D-group (74.1% vs. 50.0%; P=0.035).
  • LF Staging: Early-stage LF (prothrombin activity [PTA] 30–40%) was more common in the I-group (73.1% vs. 40.7%; P=0.018), while end-stage LF (PTA ≤20%) occurred more frequently in the D-group (25.9% vs. 3.8%; P=0.018).
  • Cirrhosis and Complications: Cirrhosis was prevalent in 43.7% of D-group patients vs. 30.8% in the I-group (P=0.033). The D-group also showed higher rates of complications, including bacterial infections (77.8% vs. 50.0%; P=0.035), renal insufficiency (25.9% vs. 3.8%; P=0.018), and gastrointestinal bleeding (22.2% vs. 0%; P=0.023).

Laboratory and Immunological Findings

Serum markers and autoantibody profiles were largely comparable between groups, with notable exceptions:

  • Alpha-Fetoprotein (AFP): AFP levels were significantly elevated in the I-group (median 109 ng/mL vs. 53 ng/mL in D-group; P=0.016). Higher AFP correlated with better prognosis, potentially reflecting active hepatic regeneration.
  • Viral Serology: Prior hepatitis B virus (HBV) exposure (HBcAb positivity: 66.7% vs. 30.4%; P=0.016) and parvovirus B19 IgG positivity (54.5% vs. 10.0%; P=0.024) were more frequent in the D-group, suggesting latent viral triggers in AIH progression.
  • Treatment Response: 80.8% of I-group patients received corticosteroids or immunosuppressants vs. 44.4% in the D-group (P=0.018). Early immunosuppressive therapy appeared beneficial in acute AIH-LF but less effective in chronic cases with cirrhosis.

Histopathological Features

Histological analysis of 23 patients (I-group:15; D-group:8) revealed distinct patterns:

  • Inflammatory Activity: Severe interface hepatitis, a hallmark of acute AIH, was prominent in the I-group (93.3% vs. 50.0%; P=0.033). Conversely, bridging necrosis and ductular reactions were common in both groups.
  • Fibrosis and Duct Injury: Advanced fibrosis (stage F3–4) was more prevalent in the D-group (50.0% vs. 6.7%; P=0.033), alongside severe bile duct injury (75.0% vs. 6.7%; P=0.002), indicative of chronicity and irreversible damage.
  • Plasma Cell Infiltration and Regeneration: Both groups exhibited plasma cell infiltration, but rosette formation and centrilobular necrosis were nonspecific.

Prognostic Implications and Clinical Insights

The study highlights critical determinants of AIH-LF outcomes:

  1. Disease Chronicity and Timing of LF Onset: Chronic AIH patients with prolonged immunosuppression faced higher risks of infections and decompensation. LF in this subgroup often occurred on a background of cirrhosis, with limited regenerative capacity.
  2. LF Subtype and Staging: SALF and early-stage LF were favorable prognostic markers, likely due to preserved hepatic reserve and responsiveness to therapy. In contrast, ACLF/SACLF and end-stage LF reflected irreversible damage and higher mortality.
  3. AFP as a Regeneration Marker: Elevated AFP (>100 ng/mL) in the I-group underscored its role as a surrogate for hepatic repair, aligning with previous studies linking AFP levels to improved survival in acute liver injury.
  4. Virological Triggers: Prior HBV and parvovirus B19 infections in the D-group suggested latent viral involvement in immune dysregulation, warranting further investigation into viral-host interactions in AIH pathogenesis.
  5. Histological Predictors: Severe interface hepatitis indicated acute, steroid-responsive inflammation, whereas advanced fibrosis and duct injury signified chronic, treatment-resistant disease.

Therapeutic and Diagnostic Considerations

Early recognition of AIH-LF subtype and stage is crucial for risk stratification. Patients with chronic AIH, cirrhosis, or delayed LF onset require vigilant monitoring for complications and timely evaluation for transplantation. In acute AIH-LF, prompt immunosuppression may prevent progression, supported by the I-group’s higher steroid usage and favorable outcomes. Conversely, chronic AIH-LF patients may benefit from combined therapies targeting fibrosis and bacterial infections.

The study underscores the need for multicenter studies to validate these findings and refine prognostic models integrating clinical, laboratory, and histopathological data.

doi.org/10.1097/CM9.0000000000001677

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