Don't be blinded by viral hepatitis in real cases

Author: Xiao Yuzhen Shao Ming Hepatobiliary and Gastroenterology Specialist Hospital of Yongji City, Shanxi Province

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Patient Zhang, female, 48 years old, Shanxi nationality
.
On August 29, 2010, the patient was admitted to our hospital
for "fatigue, dry mouth, epistaxis, and itchy skin for one year".

Present medical history: the patient developed fatigue, dry mouth, epistaxis, and itchy skin after exertion 1 year ago, which was not taken seriously
.
On July 1, 2010, he was hospitalized in a hospital for 17 days, and his liver function was checked for ALT 91U/L and ast 83U/L; HBs Ag(-), anti-HCV (+), anti-HIV(-), RPR(-), ESR 42mm/h
.
Blood routine: PLT 62×10⁹/L, Yu normal
.
Coagulation test: PTA 117%.

HCV RNA quantification < 1.
0×10<b22>3 copies/mL
.
ECG and chest x-ray are normal
.
Gastroscopy: chronic superficial gastritis
.
Hepatoprotective infusion therapy was given during hospitalization, during which the diagnosis was: (1) chronic hepatitis C; (2) Chronic gastritis
.
The patient lost 10 pounds
in 1 year.
Outpatient clinics with "(1) viral hepatitis (type C) chronic; (2) Chronic gastritis" admitted to the hospital
.
The patient was in clear consciousness, poor spirit, 1/3 less diet than normal, acceptable sleep, and normal urine
.

Epidemiological history: denial of
close contact with a person with hepatitis.
No history
of blood donation.
Vaccination history is unknown
.

Anamnesis: In 1995, he had a blood transfusion due to heavy bleeding after uterine evacuation, the specific composition and amount are unknown
.
Deny a history of hypertension, diabetes, heart disease, other infectious diseases, trauma, poisoning, drug allergy
.

Personal history: born in the local area, has not been to the epidemic area, no bad habits
.

Marriage and childbearing history: married at the appropriate age, with 1 son
.
His spouse and son are in good health
.

Menstrual history: menarche 13 years old, menstrual period 4--7 days, menstrual cycle 28-30 days, last menstrual period 2010-8-16, previous amount, color, no painful menstrual history
.

Family history: unknown
.

Physical examination: vital signs are stable
.
Clear, normal development, good spirits, physical examination cooperation
.
Liver disease appearance, mild xantis of the sclera, spider angioma (+), palmar hepatophyllum (-), no bleeding points
.
Superficial lymph nodes throughout the body are not palpable
.
Lungs (-), heart (-).

The abdomen is flat, no varicose veins of the abdominal wall, no tenderness and rebound tenderness
.
The liver is not palpated under the ribs, and the spleen is palpable
2 cm below the ribs.
Liquid wave tremor (-).

Abdominal percussion is diagnosed with mobile dullness (-), hepatic percussion pain (+), and percussion pain in both kidneys (-).

Auscultated bowel sounds 5 times/minute, and no vibrating sounds and vascular bruits were
heard.
Both lower extremities are free of edema, varicose veins, and pigmentation
.

Ancillary tests: liver function: TBil 26.
2umol/L, DBil 9.
80umol/L, IBil 16.
40umol/L, ALT 144.
0U/L, AST 107.
0U/L, ALP 578.
0U/L, GGT 992.
0U/L, ChE 2336.
7U/L, TP 82.
9g/L, Alb 43.
3g/L, GLO 39.
6g/L，TBA 7.
0umol/L，BS 5.
02mmol/L
。 Renal function, lipids, electrolytes: normal
.
Blood routine: WBC: 4.
87×10 9/L, Hb: 128g/L, PLT 64×10⁹/L.

AFP 13ng/ml，CEA 10ng/ml
。 Anti-HAV-IgM (-), hepatitis B series: total yin
.
Anti-HDV (-), anti-HEV(-), anti-HGV(-).

HBV DNA quantification < 1.
0×10 3 copies/mL <b15>and HCV RNA quantification < 1.
0×10<b20>3 copies/mL.

Coagulation series: normal
.
Thyroid function: normal
.
Urine 11 items: normal
.
ECG, chest x-ray: normal
.
Abdominal ultrasound: (1) cirrhosis splenomegaly without ascites; (2) Secondary gallbladder changes
.

• Preliminary analysis

1.
ALP and GGT in the patient's liver function are significantly increased, and chronic hepatitis C generally these two enzymes should not be so high
.
There are many clinical reasons for the elevation of these two enzymes, such as: drug-induced liver damage, alcoholic liver disease, obstructive jaundice (such as: bile duct stones, bile duct mass lesions, primary biliary cholangitis, primary sclerosing cholangitis, etc.
), are these factors combined? This patient has no long-term drug use, no history of alcohol consumption, drug-induced liver damage, and alcoholic liver disease are not considered
.
Further improve the three tests of autoimmune liver disease-related antibodies and immunoglobulins to find the cause
.

2.
Is the patient's weight loss caused by diabetes and hyperthyroidism? Combined with test results, these two disorders can be excluded
.

3.
Combined with abdominal ultrasound results: bile duct system stones can be excluded
.
There is no intrahepatic or external bile duct dilation, and obstructive jaundice is not considered
.
Perfecting contrast-enhanced CT examination of the abdomen, are there new clues?

4.
Whether there are other viral infections, such as Epstein-Barr virus, cytomegalovirus and other infections, complete the examination to exclude
.

5.
Abnormal liver function, whether there is low replication of hepatitis C virus, quantitative detection of highly sensitive hepatitis C virus, and antiviral therapy
if necessary.

• Initial diagnosis

1.
Compensatory period of cirrhosis; 2.
Viral hepatitis (type C) chronic; 3.
Chronic gastritis

Give symptomatic treatment such as liver protection and nutritional support, and continue to improve relevant examination items
.

Results return: Autoimmune liver disease antibody combination: AMA+, AMA-M₂+++, residual negative
.
IgG 1590mg/dl， IgA 246mg/dl， IgM 359mg/dl
。 Highly sensitive HCV quantification: <15 IU/mL<b22>.
CMV-IgM antibody, CMV-IgG antibody: negative, CMV-DNA ration: negative; Epstein-Barr virus shell antigen, IgM antibody: negative; Epstein-Barr virus DNA quantification: normal
.
CT with abdominal contrast: cirrhosis splenomegaly cholecystitis
.

• Final diagnosis

1.
Compensatory period of cirrhosis; 2.
Viral hepatitis (type C) chronic; 3.
Primary biliary cirrhosis; 4.
Chronic gastritis

• Follow

After discharge, the patient has been treated with oral ursodeoxycholic acid and calcium, and regularly reviewed liver function, kidney function, blood routine, coagulation series, hepatitis C virus quantification, urine 11 items, abdominal ultrasound and other items, liver function gradually normalized, the condition was stable, and follow-up
continued.

This patient has chronic hepatitis C with primary biliary cirrhosis (PBC), which is less common
clinically.
If this patient is not carefully investigated, he will mistakenly think that the liver function biochemical indicators are abnormal due to hepatitis C, thus ignoring the existence of
autoimmune liver disease - PBC.
The transmission route of hepatitis C in China is mainly blood transfusion, followed by iatrogenic infection or sexual transmission caused by surgery or injection; The anti-HCV positive rate in China is 3.
2%.

At the end of the eighties, there was a hepatitis C pandemic among professional blood donors in our country due to component blood donation, and a large number of blood patients were infected with HCV
due to the infection of blood donors.
Paid blood donors have a higher rate
of HCV infection due to multiple blood donations or component blood donations.
One of the important clinical characteristics of chronic hepatitis C is that the symptoms after infection are mild, the progression rate is slow, and the liver function indicators are mostly normal or mildly abnormal, which is not easy to be detected by patients or doctors, thus forming a large, hidden, undiagnosed chronic hepatitis C population in the society, and also forming a very dangerous hidden source of infection, which plays a very important role
in the spread of hepatitis C.
Chronic hepatitis C is insidious and "gentle", and patients have a low
rate of visits based on perceived symptoms.
Clinicians should be knowledgeable and vigilant, and high-risk patients and those with a history of blood transfusion before 1998 should be screened
for HCV RNA and hepatitis C antibodies.

With the attention of clinical doctors to hepatitis C, general hospitals have also paid attention to HCV screening, and more hepatitis C patients have been detected, and some patients need treatment
according to specific conditions 。 The advent of direct-acting antiviral agents (DAA) in 2015 has significantly benefited hepatitis C patients who need treatment, and its advantages are: easy to take, easy to store, reduce the speed of virus replication, and have epoch-making milestones for the treatment of hepatitis C
.

There are three types of autoimmune liver diseases, namely autoimmune hepatitis, PBC, and primary sclerosing cholangitis
.
This diagnosis has been used since
Ahrens EH Jr first named PBC as primary biliary cirrhosis in 1950.
PBC is a chronic non-purulent, destructive cholangitis, mainly involving the intrahepatic medium and small bile ducts, mainly in middle-aged women, often accompanied by other autoimmune diseases, especially Sjogren's syndrome and thyroid disease
。 The clinical manifestations are characterized by skin itching and jaundice, laboratory tests show elevated enzymes related to cholestasis such as ALP and GGT, immunological examinations are mainly IgM elevation, and anti-mitochondrial antibody (AMA) and its subtype M 2 (AMA-M 2) are of diagnostic significance in autoantibodies
。 The cause of the disease is unknown, but there is a large body of evidence that the disease is related
to autoimmune abnormalities.
PBC is more common in women, with a male-to-female ratio of 1:9
.
In the diagnosis of PBC, AMA is the serological marker of PBC, among which AMA-M2 has high sensitivity and specificity for PBC, which is the most prominent immunological abnormal index of this disease, and has important early diagnostic value
for PBC.

The natural history of PBC is broadly divided into four phases
.
The first stage is preclinical: AMA is positive, but there are no obvious abnormalities
in biochemical indicators.
The second stage is asymptomatic; The main manifestations are abnormal biochemical indicators, but there are no obvious clinical symptoms
.
The third stage is the symptomatic period: the patient has clinical symptoms such as fatigue and itchy skin; From the onset of symptoms, the average survival time is 5~8 years
.
The incidence of portal hypertension-related complications in symptomatic patients is 10%~20% within 10 years, which is higher than that of asymptomatic patients
.
When patients develop esophageal and gastric varices, the 3-year survival rate is only 59%, and the 3-year survival rate after the first bleeding is about 46%.

The fourth stage is the decompensation phase: the patient has clinical manifestations
such as gastrointestinal bleeding, ascites, and hepatic encephalopathy.
This stage is characterized by progressive elevation of bilirubin, and when bilirubin reaches 34.
2 umol/L, the average survival time is 4 years; When 102.
6 umol/L is reached, it marks the end stage of the patient, and the average survival time is only 2 years
.

The use of ursodeoxycholic acid (UDCA) significantly alters the natural history
of PBC.
The survival of patients with good biochemical response to UDCA was similar to that of healthy people matched for age and sex, while the long-term survival rate of patients with poor response was lower than that of
healthy controls.

PBC is not easy to detect early clinically and is easy to misdiagnose as other diseases
.
Most patients are found to have progressed to cirrhosis, even in the advanced stage, and some patients are not diagnosed
until death.
If the patient can be diagnosed within the first time of the visit, so as to take UDCA treatment early, it can significantly improve symptoms, delay the progression of the disease, reduce the mortality rate, and reduce the misdiagnosis rate
.
For middle-aged women who encounter clinical disorders with abnormal liver function, especially ALP and GGT, autoimmune liver disease-related antibody tests should be checked, and most viral markers in PBC patients are negative
.
Therefore, it is important to consider the scope of autoimmune liver disease and exclude PBC.

Clinically, there are also a small number of PBC patients with viral hepatitis such as: hepatitis B, hepatitis C, as a clinician to be bold and careful, dare to think, clear disease diagnosis as the ultimate goal, only a clear diagnosis, can have a target, so as to achieve twice the effect
with half the effort.

If the disease can be diagnosed in time at an early stage and after the standard treatment of UDCA, most patients will not necessarily develop cirrhosis, and the "cirrhosis" in the diagnostic name of "primary biliary cirrhosis" often brings great mental burden and work, life and social troubles
to patients.
Therefore, domestic and foreign experts jointly published an article suggesting that "primary biliary cirrhosis" be renamed "primary biliary cholangitis (PBC)"
.
Since the name "primary biliary cholangitis" has not yet been officially accepted, it is recommended that the diagnosis of "primary biliary cholangitis" be gradually promoted in the future.

The "Guidelines for the diagnosis and treatment of primary biliary cholangitis (2021)" has been released, in which primary biliary cholangitis (formerly known as primary biliary cirrhosis), because this patient is a patient in 2010, so the name
of the previous diagnosis - primary biliary cirrhosis is used.

Early diagnosis of PBC is of great significance and deserves the attention of every clinician!