Acute Liver Failure by Autoimmune Hepatitis (AIH) and Liver Cirrhosis in Adolescent Patient: Case Report

  

    
Laboratory test 
    
Oct 2000 
    
May 2005 
    
Mar 2016 
    
Apr 2016 
    
Jul 2016 
  
  

    
Hemoglobin
    
14.5 g/dl
    
13.2 g/dl
    
15.7 g/dl
    
---
    
10.2 g/dl
  
  

    
hematocrit
    
43.5 %
    
41.5 %
    
40 %
    
---
    
38 %
  
  

    
leucocytes
    
9.2 103/µl
    
7.6 103/µl
    
9.2 103/µl
    
---
    
10.2 103/µl
  
  

    
platelets
    
256 103/µl
    
232 103/µl
    
256 103/µl
    
---
    
148 103/µl
  
  

    
Glucose
    
80 mg/dL
    
84 mg/dL
    
72 mg/dL
    
---
    
89 mg/dL
  
  

    
BUN
    
10 mg/dL
    
13 mg/dL
    
20 mg/dL
    
---
    
31 mg/dL
  
  

    
Urea
    
19.4 mg/dL
    
22 mg/dL
    
21 mg/dL
    
---
    
50 mg/dL
  
  

    
creatinine
    
0.3 mg/dL
    
0.45 mg/dL
    
0.5 mg/dL
    
---
    
0.8 mg/dL
  
  

    
Total protein
    
7.6 g/dl
    
6.9 g/dl
    
7.0 g/dl
    
---
    
4.9 g/dl
  
  

    
Albumin
    
3.2 g/dl
    
2.9 g/dl
    
4.3 g/dl
    
---
    
1.3 g/dl
  
  

    
Globulin
    
5.5 g/dl
    
4.5 g/dl
    
4.5 g/dl
    
---
    
2.2 g/dl
  
  

    
Total bilirubin
    
3.4 mg/dl
    
3.5 mg/dl
    
3.0 mg/dl
    
---
    
15.6 mg/dl
  
  

    
Direct bilirubin
    
1.8 mg/dl
    
2.3 mg/dl
    
2.0 mg/dl
    
---
    
10.2 mg/dl
  
  

    
Indirect bilirubin
    
1.6 mg/dl
    
1.2 mg/dl
    
1.0 mg/dl
    
---
    
5.4 mg/dl
  
  

    
AST
    
452 UI/dl
    
436 UI/dl
    
105 UI/dl
    
---
    
2290 UI/dl
  
  

    
ALT
    
880 UI/dl
    
540 UI/dl
    
130 UI/dl
    
---
    
3190 UI/dl
  
  

    
GGT
    
425 UI/dl
    
479 UI/dl
    
220 UI/dl
    
---
    
670 UI/dl
  
  

    
DHL
    
302 UI/dl
    
350 UI/dl
    
220 UI/dl
    
---
    
600 UI/dl
  
  

    
AF
    
678 UI/dl
    
714 UI/dl
    
213 UI/dl
    
---
    
890 UI/dl
  
  

    
Cholesterol
    
100 mg/dl
    
130 mg/dl
    
120 mg/dl
    
---
    
100 mg/dl
  
  

    
triglycerides
    
88 mg/dl
    
95 mg/dl
    
90 mg/dl
    
---
    
70 mg/dl
  
  

    
Calcium
    
9.2mg/dL
    
10.0 mg/dL
    
9.8 mg/dL
    
9.9 mg/dL
    
8.5 mg/dL
  
  

    
Potassium
    
4.3 mmol/l
    
5.0 mmol/l
    
6.0 mmol/l
    
5.5 mmol/l
    
4.3 mmol/l
  
  

    
Sodium
    
139 mmol/l
    
145 mmol/l
    
100 mmol/l
    
137 mmol/l
    
138 mmol/l
  
  

    
Chlorine 
    
109 mmol/l
    
102 mmol/l
    
103 mmol/l
    
99 mmol/l
    
105 mmol/l
  
  

    
PT
    
22.0 seg
    
23.0 seg
    
15.0 seg
    
---
    
35.0 seg
  
  

    
PTT
    
31.4 seg
    
32.0 seg
    
25.0 seg
    
---
    
45.0 seg
  
  

    
INR
    
1.8
    
1.9
    
1.13
    
---
    
2.3
  
  

    
IgG
    
5050 mg/dl
    
5220 mg/dl
    
---
    
---
    
---
  
  

    
IgA
    
400 mg/dl
    
450 mg/dl
    
---
    
---
    
---
  
  

    
ANA
    
Negative
    
---
    
---
    
---
    
---
  
  

    
SMA
    
Negative
    
---
    
---
    
---
    
---
  
  

    
LKM-1
    
1:40 Positive
    
---
    
---
    
---
    
---
  
  

    
SLA
    
Negative
    
---
    
---
    
---
    
---
  

Table 1: Laboratory test results.

After biopsy, immune studies showed (Table 1): IgG 5050 mg/ dl (reference value: 690-1620), IgA 400 mg/dL (reference value: 70- 380); T/B lymphocytes and subclasses showed no abnormalities; antinuclear antibodies (ANA) negative, anti-smooth muscle negative (SMA), anti-microsomal against liver and kidney (LKM- 1) positive, anti-soluble liver antigen (SLA) negative; diagnosis of type 2 AIH (AIH-2) was established. Prednisone at dose of 2 mg/kg/ day and azathioprine (AZA) 0.5 mg/kg/day was started like initial treatment with improvement at four weeks, jaundice and epistaxis disappear; however she had 5.5 kg weight gain and hair loss as steroid complication, dose of prednisone was decreased at 1 mg/kg/day and subsequently to 5 mg/day with maintenance of AZA (0.5 mg/kg/day). AIH remission was achieved by normalizing levels of transaminases and bilirubin. Five years after diagnosis, patient was admitted to emergency room for abdominal pain, jaundice, dark urine and acholia. Blood test showed (Table 1): direct bilirubin 2.3 mg; indirect bilirubin 1.2 mg; ALT 540 IU; AST 436 IU; LDH 350 IU; GGT 479 IU; PT 23 sec; PTT 32 sec; IgG 5220 mg/dL (reference value: 690-1620), AIH relapse was diagnosed and prednisone dose was increased to 2 mg/kg/day and AZA 2 mg/kg/day, with improvement after two weeks of treatment. A new liver biopsy reported: autoimmune hepatitis with moderate inflammatory activity, portal fibrous and irregular nodular liver parenchyma.

At age 19, 16 years after diagnosis and medical management, was admitted into emergency room for diarrhea, vomiting, disorientation, dyspnea moderate, orthopnea and edema since a month ago; laboratories reported (Table 1): Hb 15.7 g/dl; WBC 9.2 10³/L; platelets 256,000/L; glucose 72 mg/dl; urea 21 mg/dl; creatinine 0.5 mg/dL; albumin 4.3 g/dl; AST 105 IU; ALT 130 IU; LDH 220 IU; Sodium 100 mmol; Potassium 6.0 mmol; chlorine 98 mmol; PT 15 sec; PTT 25 sec; INR 1.13. Severe hyponatremia was detected in blood test. Initially severe hyponatremia was confirmed and use of hypertonic saline was considered, subsequently continued with isotonic saline, intravenous diuretic, achieving a negative balance of water and a positive sodium balance during next days; required intravenous potassium replacement. Patient was discharged 10 days later with normal serum sodium (137 mmol) without neurological disorders; AIH treatment with prednisone 10 mg/day.

Three months later she was admitted to emergency room with jaundice, nausea, vomiting and disorientation, laboratories showed (Table 1): Hb 10.2 g/dl; WBC 10.2 10³/L; platelets 148000; glucose 89 mg/dl; urea 50 mg/dl; creatinine 0.8 mg/dl; albumin 1.3 g/dl; bilirubin direct 10.2 mg; indirect bilirubin 5.4 mg; AST 2290 IU; ALT 3190 IU; LDH 600 IU; sodium 138 mmol; potassium 4.3 mmol; chlorine 105 mmol; PT 35 sec, PTT 45 sec; INR 2.3. Once stabilized, acute liver failure secondary to AIH was diagnosed, a third liver biopsy reported: autoimmune chronic hepatitis, liver necrosis, severe inflammatory activity and cirrhosis. Aggressive treatment was started with steroids and immunosuppressant (cyclosporine). Six hours later development a severe hepatic encephalopathy; despite support measures implemented, patient presented cardiorespiratory arrest without response to advanced support and died five days after admission.

Discussion

In this clinical case, disease started with clinical and biochemical manifestations of liver failure, initially was considered secondary to acute viral hepatitis as differential diagnosis but serological markers were negative. Due to persistence of symptoms for more than six months a liver biopsy was done. Chronic hepatitis is defined as a necro-inflammatory liver syndrome, which persists for at least 6 months without remission of symptoms and biochemical alterations [8]. In our case, viral etiology was discarded by negativity of viral markers. Autoimmune etiology is supported by clinical and biochemical features, histologic findings, hypergammaglobulinemia and disease evolution.

Definitive diagnosis of AIH in our patient was established on basis of clinical, laboratory and histopathological criteria defined by IAIHG. Some of these criteria are directly related to diagnosis and others have been associated with worse prognosis [9]. In diagnostic criteria (Table 2), ANA/SMA/LKM-1 has been set up as positive 1:40 for adults, but for children, 1:20 is enough for ANA/SMA, and 1:10 for LKM-1 [10]. SLA positivity is related to severe course and higher tendency to relapse [11].

  

    
Immunoglobulin G (IgG) 
      
IgG Higher than normal
      
IgG Higher than 1.10 times normal
    
 
      
1 point
      
2 points
  
  

    
Autoantibodies 
      
ANA o SMA =1:40
      
ANA o SMA =1:80
      
LMK =1:40
      
SLA positive
    
 
      
1 point
      
1 point
      
2 points
      
2 points
  
  

    
Chronic hepatitis histology 
      
AIH compatible
      
AIH typical
    
 
      
1 point
      
2 points
  
  

    
Absence of viral    hepatitis 
    
2 points
  
  

    
Score 
      
AIH probable =6 points
      
AIH diagnosis =7 points
  
  

    
AIH: autoimmune hepatitis, ANA: antinuclear antibodies, SMA:    anti-smooth muscle, LKM-1: anti-microsomal against liver and kidney, SLA:    anti-soluble liver antigen 
  

Table 2:  Simplified diagnostic criteria for AIH [6].