"Behind the scenes" of repeated abnormal liver function | Case Sharing

Author: Dan Hu Shao-ming Shao Yan Xiao Yuzhen Yongji City, Shanxi Province hepatobiliary stomach specialist hospital this article is the author's permission NMT Medical publish, please do not reprint without authorization.

Introduction There are many reasons for abnormal liver function in clinic.
The most common factors in our country are viral hepatitis, alcohol, drugs, obesity and other factors.
What are the reasons for today's cases? Let us follow the author and find out! Case introduction The patient, Li, female, 44 years old, from Shanxi, was admitted to the hospital on October 4, 2020 (the last hospitalization in our hospital) due to "repeated abnormal liver function for more than 1 year".

History of present illness: The patient developed fatigue, nausea and upper abdominal discomfort after taking multiple drugs for "pruritus skin" 1 year ago; on June 10, 2019, he checked liver function in a hospital in Tianjin: TB: 182.
60 umol/L, DB: 130.
52 umol /L, ALT: 756.
0U/L; AST: 1006.
6U/L; HBsAg(-); abdominal color Doppler ultrasound showed: cholecystitis.

Then checked into our department to check liver function: TB: 296.
00µmol/L, DB: 187.
50µmol/L, ALT: 776.
0U/L, AST: 971.
0U/L, ALP: 171.
0U/L, GGT: 94.
0U/L, ChE: 3602.
0U/L, Alb: 36.
2g/L; coagulation series: PT: 22.
72 (Sec), INR: 1.
88.

Viral hepatitis markers: all negative; abdominal color Doppler ultrasound showed: weak echo in the gallbladder.
Consider gallbladder polyps; cyst wall edema. The initial diagnosis is: chronic plus subacute liver failure, drug-induced liver injury (hepatocellular injury type), acute RUCAM 5 points (possibly), severity level 3; autoimmune hepatitis? Give liver protection, methylprednisolone, albumin, etc.
to support symptomatic treatment; before discharge (on the 22nd day of hospitalization) liver function review: TB: 47.
00 µmol/L, DB: 25.
50 µmol/L, IB: 21.
50umol/L, ALT: 240.
0U/L, AST: 101.
0U/L, GGT: 157.
0U/L, ChE: 3025.
4U/L, Alb: 34.
3g/L; oral methylprednisolone tablets 8mg after discharge, liver function review in the field after 4 weeks Stop the medication by itself normally.

After stopping the drug for 2 months, the liver function was rechecked; there was no obvious cause for abnormal liver function 3 times in the following six months: TB: 34.
10-280.
00 µmol/L, DB: 8.
20-194.
00 µmol/L, ALT: 117.
0-257.
0U/L , AST: 88.
0-1191.
0U/L, GGT: 61.
0-147.
0U/L, Alb: 32.
2-47.
0g/L; PT: 16.
72-22.
72Sec; INR: 1.
52-1.
88; 8 items of autoimmune liver disease antibodies: normal ; ANA: 1:80-1: 640 (cytoplasmic type), AMA, ASNA: normal.

Immunoglobulin IgG: 20.
32g/L, immunoglobulin IgM, IgA: normal.

Cytomegalovirus, Epstein-Barr virus, Ceruloplasmin: normal; iron four: normal.

Abdominal color Doppler ultrasound showed: large gallbladder, cyst wall edema; deposits in the cavity.

ECG: non-specific T wave abnormalities.

Repeated monitoring of fasting and 2 hours postprandial blood glucose levels were higher than the normal range.
After administration of insulin aspart (Novoray) + recombinant insulin glargine, blood glucose control was acceptable. 2020-09-28 review results showed: liver function: TB: 49.
50 µmol/L, DB: 26.
90 µmol/L, IB: 22.
60 µmol/L, ALT: 124.
0U/L, AST: 85.
0U/L, GGT: 108.
0 U/L, ChE: 2318.
4U/L, TP: 59.
1g/L, Alb: 33.
6g/L; Glu: 9.
37mmol/L; coagulation series: normal; blood routine: normal; continue methylprednisolone 8mg combined with thioazole Purine tablets (Yimulan) 50mg, once a day, taken until now; blood sugar control is not good, give long-acting insulin (recombinant insulin glargine).

Seven days before admission, he felt fatigue, abdominal distension, and liver discomfort.
He had a diet less than 1/3 of the normal amount.
He had a good sleep, and his stool and urination were basically normal.

Epidemiological history: Denies the history of close contact with patients with hepatitis.

He had been transfused with albumin and denied a history of blood transfusion.

Denies the residence history and patient contact history in the new coronavirus pneumonia epidemic area, and the history of vaccination is unknown.

Past history: More than 3 years of contact with mechanical parts (with a slight peculiar smell).

Denied history of hypertension, heart disease, history of exposure to infectious diseases such as typhoid fever, tuberculosis, and history of trauma.

Denies the history of poisoning and has a history of penicillin allergy.

Personal history: Born locally, have never been to an epidemic area, and have no bad habits.

Menstrual history: Menarche is 14 years old, menstrual period is 4-7 days, menstrual cycle is 28-30 days, last menstruation is 2020-09-26, previous volume and color are normal, no history of dysmenorrhea.

Marriage and childbirth history: married at the age of 25 and had 1 child.

His spouse and son are in good health.

Family history: Deny a history of related diseases in the family.

Physical examination: body temperature: 36.
4℃, pulse rate: 76 beats/min, breathing: 19 beats/min, blood pressure: 124/70mmHg, weight: 60kg.

Consciousness, poor spirit, moderate yellowing of skin and sclera, KF ring (-); no spider moles and liver palms were seen.

There was no palpable swelling of the superficial lymph nodes throughout the body.

No palpable swelling of the thyroid gland on both sides.

Breath sounds in both lungs were clear, and no dry or wet rales were heard.

The heart rate was 76 beats/min, the heart rhythm was uniform, and no murmur was heard in the auscultation area of ​​each valve.

The abdomen was flat, no localized bulge, no varicose veins and gastrointestinal peristaltic waves, and no surgical scars.

Abdomen: tenderness, rebound pain (-), Murphy sign (-), no bump in the abdomen.

The liver and spleen were not touched under the ribs.

Liquid wave tremor (-).

Mobile dullness (-), percussive pain in the liver area (+).

Bowel sounds 5 times/min.

Pitting edema of both lower limbs (-).

The muscle strength and muscle tension of the limbs were normal, the physiological reflex was normal, and the pathological reflex was not elicited.

 Examination results after admission: liver function: TB: 34.
10µmol/L, DB: 18.
20µmol/L, ALT: 117.
0U/L, AST: 88.
0U/L, GGT: 108.
0U/L, ChE: 2317.
8U/L, TP: 58.
2g/L, Alb: 33.
3g/L, Glu: 8.
51mmol/L; coagulation series: normal; blood routine: normal; abdominal color Doppler ultrasound shows: 1.
The liver parenchyma light spot is slightly thickened with gallbladder stones; intracavitary bile Stasis; now oral methylprednisolone 8mg combined with azathioprine tablets (Imulan) 50mg, 1 time/day, insulin aspart (Novoray) + recombinant insulin glargine, rabeprazole sodium enteric-coated capsules 10mg, take every other day Once; calcitriol capsules (Luo Gaiquan) 1 tablet, once a day, orally.

Analysis and diagnosis of this patient analysis: 1.
A middle-aged woman who has repeated episodes of bilirubin and transaminase in liver function 4 times.
Symptoms and test indicators improved significantly after using methylprednisolone, and rebounded after stopping the drug; the first time there was a clear history of medication, There is no obvious medication history for the next 3 times, which is consistent with drug-mediated immune damage; is it drug-induced autoimmune hepatitis (DIAIH)? 2.
Initial diagnosis: 1) Autoimmune hepatitis? 2) Hypoproteinemia 3) Type 2 diabetes 4) Chronic cholecystitis 5) Gallbladder stones are the reason for the repeated increase of bilirubin and transaminase, and further confirm the diagnosis. Liver puncture histopathological examination under color Doppler ultrasound guidance on 2020-10-04: Take 1 piece of liver tissue (2.
0cm, as shown in the figure below), and send the specimen to the Pathology Department of China-Japan Friendship Hospital.

Figure 1 Liver biopsy tissue liver histopathological examination under microscope: There are 18 medium and small portal areas in the slice, some of which are connected, mild to moderate mixed inflammatory cell infiltration in the interstitium with obvious interface inflammation, and more plasma cells ( Figure 2 upper left, HE).

The epithelium of the small bile ducts is mildly irregular, epithelial loss and vacuolation are occasionally seen, and the thin bile ducts are mildly proliferated.

The structure of the lobules was destroyed, and multiple portal areas were close to one side, and regenerated hepatocyte clusters were seen in them (right side of Figure 2, net staining + Masson).

In addition, a bridging necrosis zone is seen in the lobules, and the internal tissue is relatively loose (Figure 2, upper right, HE).

A small number of hepatocytes in the liver parenchyma around the portal area and the necrotic zone developed bullous lipidosis (Figure 2, upper right, HE).

Fig.
2 Pathological diagnosis of liver histopathological examination results: (Liver puncture) Moderate lobular hepatitis (most of the bridging necrosis zones of different old and new) accord with AIH.

Discussion Autoimmune hepatitis (AIH) is an inflammation of the liver parenchyma mediated by an autoimmune response against liver cells, with positive serum autoantibodies, hyperimmune globulin G (IgG) and (or) gamma globulinemia , Liver histology has the characteristics of interface hepatitis, if not treated, it can often lead to cirrhosis and liver failure.

The clinical manifestations of AIH are diverse, generally chronic and insidious onset, but can also be manifested as acute onset, and even cause acute liver failure.

Laboratory examination: 1.
Serum biochemical indicators: The typical abnormal serum biochemical indicators of AIH are mainly manifested as liver cell injury type changes, increased AST and ALT activities, while ALP and GGT levels are normal or slightly increased; 2.
Immunological examination: The increase of serum immunoglobulin IgG and gamma globulin is one of the characteristic serum immunological changes of AIH.

Serum IgG levels can reflect the degree of inflammation in the liver, and can gradually return to normal after immunosuppressive treatment.

Therefore, this indicator is not only helpful for the diagnosis of AIH, but also has an important reference value for the detection of treatment response.
It should be routinely tested during initial diagnosis and treatment follow-up. 3.
Autoantibodies and typing: There are one or more high titers of autoantibodies in the serum of most AIH patients, but most of these autoantibodies lack disease specificity.

4.
Liver histological examination: It is very important for the diagnosis and treatment of AIH.
It can clearly diagnose and accurately evaluate the classification and staging of liver disease.
Most autoantibody-negative patients have about (10%-20%) serum IgG and (or) gamma globulin.
The level is not obvious, and liver histological examination may be the only basis for diagnosis.

The characteristic liver histological manifestations of AIH include interface hepatitis, lymphoplasma cell infiltration, hepatocyte rosette-like changes, lymphocyte penetration, and central lobular necrosis.

 The overall goal of AIH treatment: to obtain remission of liver histology, prevent the development of liver fibrosis and liver failure, prolong the survival of patients and improve the quality of life of patients.

The first choice for treatment of AIH patients: Generally, the combination therapy of prednisone (long) and azathioprine is preferred.
Combined treatment can significantly reduce the dose of prednisone (long) and its adverse reactions; the reduction of glucocorticoids should follow the principle of individualization It can be adjusted appropriately according to the serum biochemical indicators and the improvement of IgG levels.

AIH patients with jaundice can be treated with glucocorticoids to improve their condition first, and after the total bilirubin decreases significantly, azathioprine combination therapy can be considered.

Note: 1.
AIH patients who have been treated with glucocorticoids for a long time develop diabetes, osteoporosis, abnormal fat metabolism, etc.
, it is recommended that baseline bone mineral density monitoring be performed before treatment, and annual monitoring and follow-up, and appropriate supplementation of vitamin D3 and calcium; monitoring; blood sugar.

2.
The complete blood count should also be monitored during the administration of azathioprine to prevent the occurrence of bone marrow suppression.

It is recommended to test its TPMT activity (safety test for azathioprine drugs).

The results of this patient are as follows: Risk warning: the activity is normal, and the risk of toxicity is small when treated with standard doses of purine drugs.

Follow up on 2020-12-08 the patient has no symptoms, recheck liver function: TB: 21.
10mmol/L, DB: 7.
4mmol/L, ALT: 70.
0U/L, AST: 53.
0U/L, ALP: 45.
0U/L, GGT: 39.
0U/L; Alb: 38.
3g/L; blood routine: normal; three immunoglobulins: IgG: 12.
53g/L (reference range 7.
0-16.
00).

Abdominal color Doppler ultrasound showed: 1.
The light spot of liver parenchyma was slightly thickened 2.
Gallbladder stones.

Oral methylprednisolone 7mg combined with azathioprine tablets (Imulan) 50mg, 1 time/day, insulin aspart (Novoray) + recombinant insulin glargine, rabeprazole sodium enteric-coated capsules 10mg, take once every other day; bone Triol capsules (Luo Gaiquan) 1 tablet, once a day.

On February 22, 2021, due to poor blood sugar control, methylprednisolone tablets were discontinued, and Budesonide capsules 3mg, 2 times a day, and azathioprine tablets (Imulan) 50 mg, 1 time a day.

Liver function review on March 22, 2021: TB: 15.
60mmol/L, DB: 4.
2mmol/L, ALT: 52.
0U/L, AST: 40.
0U/L, ALP: 70.
0U/L, GGT: 32.
0U/L ; Alb: 41.
3g/L; blood routine: normal.

Insulin Aspart (Novoray) + Recombinant Insulin Glargine was gradually reduced, and blood glucose control was acceptable on an empty stomach and 2 hours after a meal.
The patient had no symptoms and continued follow-up.