The PBC diagnosis is based
on 3 criteria;
- Serum ALP increase, which is longer than six months and indicates cholestasis,
- By indirect immunofluorescence method,> 1:40 AMA (+),
- Histology of the liver compatible with the disease
If the other two criteria
are compatible but AMA is negative, then AMA-negative PBC is mentioned. AMA is positive
in 90-95% of patients.
Liver biopsy is necessary
in the following situations.
- When staging is required,
- AMA (-) and / or ALP is normal.
- If there is an increase in ALP levels and AMA is positive, the necessity of biopsy is controversial.
If the single biopsy finds
that there are signs of different stages of the disease, the highest stage is
considered.
Staging
Stage 1: Portal ducts
predominantly have lymphocytic infiltrates. There are loss of septal and
interlobular bile ducts (<100 μm) and non-caseating granulomas in the
absence of sarcoidosis or tuberculosis.
Stage 2: Peripheral
inflammatory infiltrate, cholangitis, granuloma, proliferation in ducts.
Stage 3: Septal or
bridging necrosis, ducopenia (more than half of intralobular bile ducts
disappeared) and copper depletion in periportal hepatocytes.
Stage 4: Severe cirrhosis
Non-caseating epithelioid
granulomas are not present in other autoimmune diseases. The clinical
significance is not yet known.
Clinical
findings
The majority of patients
(20-60%) are diagnosed before clinical manifestations occur. Interestingly,
somehow, asymptomatic patients are older than symptomatic patients.
Fatigue is the most common
symptom. The second common symptom is PRURITIS.
It is usually diffuse.
Typically, itching worsens at night. Fabricated cotton also worsens the itch.
Itching often occurs in the first pregnancy
and continues after birth.
Recent studies (2011) focus on the pruritic
role of Lysophosphatidic acid (LPA), a potent neuronal
inhibitor, in cholestasis.
Secondary metabolic bone disease can be seen
in PBC. Bone density should be measured every 2 years and metabolic bone
disease treatment (calcium, vitamin D) should be observed.
Dyslipidemia can be up to 85% in patients with
PBC.
More than 50% of untreated patients develop
portal hypertension during a 4-year follow-up period.
The risk of having HCC increased.
Total immunoglobulin level may be normal but
IgM fraction may be elevated.
Unlike primary sclerosing cholangitis, PBC has
no association with cholangiosarcoma.
70% of patients have another autoimmune
disease at the same time.
Conditions such as keratoconjunctivitis sikka,
reynaud phenomeni, limited cutaneous systemic sclerosis are more frequent.
Risk
Factors for PBS
|
Female gender
(10: 1)
|
PBS family
history
|
The presence of
non-PBS autoimmune disease
|
Pregnancy
|
Smoking history
|
Recurrence or
recurrence of vaginal infection,
|
Tonsillectomy
|
Frequent use of
hair dyes and nail dyes
|
Previous
surgical history (such as appendectomy, uterine surgery)
|
Hepatitis A
history
|
Contraceptive
Pill use
|
Treatment
The only drug approved by the FDA in PBS
treatment is Ursodeoxycholic acid (UDCA).
UDCA forms 4% of the bile acid pool and is
more hydrophilic than other bile acids.
The most common side effect is diarrhea.
How does UDCA work?
It modifies the bile acid pool.
It reduces the level of proinflammatory
cytokines.
UDCA reduces the degree of apoptosis and
levels of vasoactive mediators.
The UDCA dose varies from 13-20 mg / kg as
needed.
The use of immunosuppressive /
immunomodulatory drugs (azothiopurine, cyclosporine, penicillamine, and
colchicine) is not recommended if autoimmune hepatitis-PBC overlap is not
present. If these drugs should be given in overlapping situations, they should
be given in combination with UDCA.
Methotexsat can provide additional benefits in
some subgroups of PBC when combined with UDCA.
Especially in early-stage patients, the
long-term use of Corticosteroids and fibrates is not convincing.
Recent data suggest that B-cell depletion
therapy may be helpful in PBC patients who are resistant to UDCA treatment.
Orthotropic liver transplantation
Prognosis
The most reliable predictor of prognosis in
PBC is the serum bilirubin level.
Within 10 years after diagnosis, 26% of
patients develop liver failure.
Median survival time after diagnosis in PBC is
9.3 years.
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