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11 Şubat 2017 Cumartesi

PBC - Primary biliary cirrhosis


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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