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University of sulaimani
College of pharmacy
Department of clinical pharmacy and therapeutic
Primary biliary cirrhosis associated with
gallstone
Prepared by : Muhammad Koksh Sdiq

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Q : 45 year old lady presented with excessive fatigue for more than one year ,
annoying nocturnal pruritus and O/E there was clubbing of finger , dark skin and
deep jaundice .the spleen was 4cm below costalmargin.
Answer: Because of the presence of feature of obstructive jaundice and
splenomegaly this make the diagnosis of primary biliary cirrhosis is the most likely
diagnosis anyhow I need to do certain diagnostic investigation include:
 Antimitochondrial antibody titer. An Antimitochondrial antibody titer ≥1:40
is the serologic hallmark for the presence of primary biliary cirrhosis and in
90% to 95% of protein.
 Serum alkaline phosphate.
 Y-glutamatyltransferase values are usually elevated ten times or more above
normal.
 Serum bilirubin level increases mainly direct.
 The diagnosis is confirmed by liver biopsy, which characteristically shows
nonsuppurative cholangitis plus finding ranging from bile duct lesions to
cirrhosis.
Treatment:
 Ursodeoxycholic acid improves the biochemical profile , reduces pruritus,
decreases progression to cirrhosis and delays the need for liver
transplantation. Therapy is usually continued indefinitely.
 Liver transplantation is considered for patients with intractable pruritus or
complication from cirrhosis , and long term outcomes tend be better than
outcomes.

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Primary BiliaryCirrhosis(PBC)
What is primary biliary cirrhosis?
Primary biliary cirrhosis, or PBC, is a chronic, or long-term, disease of
the liver that slowly destroys the medium-sized bile ducts within the
liver. Bile is a digestive liquid that is made in the liver. It travels through
the bile ducts to the small intestine, where it helps digest fats and fatty
vitamins.
In patients with PBC, the bile ducts are destroyed by inflammation. This
causes bile to remain in the liver, where gradual injury damages liver
cells and causes cirrhosis, or scarring of the liver. As cirrhosis
progresses and the amount of scar tissue in the liver increases, the liver
loses its ability to function. Cirrhosis also prevents blood from the
intestines from returning to the heart.
PBC advances slowly. Many patients lead active and productive lives for
more than 10 to 15 years after diagnosis. Patients who show no
symptoms at the time of diagnosis often remain symptom-free for years.
Patients who have normal liver tests on treatment may have a normal life
expectancy. PBC is a chronic illness and may lead to life-threatening
complications, especially after cirrhosis develops.
What are the signs and symptoms of PBC?
Many people with PBC do not have symptoms (~50% asymptomatic at
diagnosis), especially in the early stages of the disease. When symptoms
do occur the most common is pruritus, or intense itching of the skin,
often in the arms, legs and back. Other symptoms may include fatigue,
jaundice, fluid build-up in the ankles and abdomen, and darkening of
the skin and collection of fatty deposits in the skin around the eye.
Jaundice, is an indication of how far the disease has progressed.
Several other disorders often occur with PBC. The most common is
problems with the tear and salivary glands, causing DRY EYES or
mouth( Sjögren's syndrome) . Arthritis and thyroid problems may also
be present. Renal stones and gallstones may develop. Bone softening
and fragility leading to fractures can occur in late stages of the disease.

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Gallstones and bile duct stones: If cirrhosis prevents bile from flowing
freely to and from the gallbladder, the bile hardens into gallstones.
Symptoms of gallstones include abdominal pain and recurrent bacterial
cholangitis—irritated or infected bile ducts. Stones may also form in and
block the bile ducts, causing pain, jaundice, and bacterial cholangitis.
What causes primary biliary cirrhosis?
The causes of primary biliary cirrhosis are unknown. Most research
suggests it is an autoimmune disease. In primary biliary cirrhosis, the
immune system attacks the small bile ducts in the liver.
Genetics, or inherited genes, can make a person more likely to develop
primary biliary cirrhosis. In people who are genetically more likely to
develop primary biliary cirrhosis, environmental factors may trigger or
worsen the disease, including
 exposure to toxic chemicals
 smoking
 infections
Genetics can also make some people more likely to develop other
autoimmune diseases, such as
 autoimmune hepatitis
 Sjögren’s syndrome,
 autoimmune thyroid dysfunctions
What are the complications of primary biliary cirrhosis?
Most complications of primary biliary cirrhosis are related to cirrhosis and start
after primary biliary cirrhosis progresses to cirrhosis. In some cases, portal
hypertension and esophagealvarices may develop before cirrhosis , Edema and
ascites , Varices ,Splenomegaly, Hepatic encephalopathy ,Metabolic bone
diseases. Gallstonesandbile duct stones, Steatorrhea, Liver cancer.

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Investigations
 FBC is often normal but ESR is elevated.
 Abnormal LFT s are usual but not invariable:
 Alkaline phosphatase i s usually elevated as PBC is a cholestatic condition.
 Less consistently , transaminases are raised.
 Bilirubin is often normal at first but rises as the disease progresses. Rising
bilirubindemonstrates disease progression and heralds liver failure.
 Partial thromboplastin time (PTT) and albumin are normal until a late
stage.
 IgM is raised.
 Lipid level s and cholesterol level s are raised i n 85% but risk of coronary
heart disease (CHD) is not raised as high-density lipoprotein (HDL)
cholesterol is elevated.
 Autoantibodies are characteristic:
 The most specific to PBC are antimitochondrial antibodies (AMAs), present
i n 90-95% of affected individual s (and 0.5% of normal control s, giving a
specificity of over 98%.)Evidence suggests that this anti body is directly
involved in the pathological process.
 A round 0.5% of the general population is positive for AMA s. Studies
suggest that fewer than10% of patients with positive AMAs will develop
PBC, although almost all patients with PBC have positive AMAs.
 About 35% also have antinuclear anti bodies.
 There may also be other autoantibodies, especially related to the
thyroid.Thyroid function should be assessed and monitored.
 Imaging of the liver is useful to exclude causes of obstruction like stones.
Ultrasound is most commonly used but CT and M RI scanning may be
employed. As the disease progresses there may be features suggestive of
portal hypertension and cirrhosis.
 Cholangiography is occasionally helpful in order to exclude primary
sclerosing cholangitis.
 Transient elastography is a non-invasive tool to evaluate the degree of liver
fibrosis.
 Finally , liver biopsy is required to stage the disease. Histology will
demonstrate chronic non suppurative cholangitis of the interlobular and
septal bile ducts.

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How is PBC diagnosed?
Because many PBC patients have no symptoms, the disease is often discovered
through abnormal results on routine liver blood tests. A health care provider may
use the following tests to diagnose primary biliary cirrhosis:
a medical and family history , a physical exam , blood tests , imaging tests , a liver
biopsy
A health care provider usually bases a diagnosis of primary biliary cirrhosis on two
out of three of the following criteria:
 a blood test showing elevated liver enzymes(high alkaline phosphatase,
elevated AST, ALT)
 a blood test showing the presence of anti-mitochondrial antibodies (AMA)
tests ,This test is positive in nearly all PBC patients , antinuclear antibody
(the M2-IgG antimitochondrial antibody is the most specific test)
 Ultrasound exams and a liver biopsyshowing signs of the disease in which a
small sample of liver tissue is removed with a needle, may also be
performed.
Goals of treatment
 Slow disease progression
 Treat complications
Course and cure of the disease:
- no known cure, but medication may slow the progression
- ursodeoxycholic acid (Ursodiol) is the most frequently used treatment. This
helps reduce the cholestasis and improves blood test results (liver function
tests).
- alcoholic beverages are contraindicated.
- in advanced cases, a liver transplant, if successful, results in a favourable
prognosis.
- multivitamins (esp. Vitamin D) and calcium are also recommended as
patients with PBC have poor lipid-dependent absorption of Vitamins A, D,
E, K.

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Treatment of Symptoms and Complications
- Itching. Antihistamines. However, antihistamines often cause drowsiness,
and a personshould take antihistamines just before bedtime to help with
nighttime itching. cholestyramine which reduces cholesterol in the blood.
- Dry eyes and mouth. artificial tears and saliva substitutes, respectively.
pilocarpine or cevimeline . People who have difficulty with dry eyes should
see an ophthalmologist. People with dry mouth should have regular dental
exams.
- Portalhypertension. a beta-blocker or nitrate to treat portal hypertension.
- Varices. Beta-blockers. Bleeding in the stomach or esophagus requires an
immediate upper endoscopyPeople who have had varices in the past may
need to take medication to prevent future episodes.
- Edema and ascites. diuretics—medications that remove fluid from the
body—to treat edema and ascites. A health care provider may remove large
amounts of ascitic fluid from the abdomen and check for spontaneous
bacterial peritonitis. antibiotics to prevent infection, oral antibiotics;
however, severe infection with ascites requires intravenous (IV) antibiotics.
- Hepatic encephalopathy. cleansing the bowel with lactulose, a laxative
given orally or as an enema—a liquid put into the rectum. add antibiotics to
the treatment. Hepatic encephalopathy may improve as other complications
of cirrhosis are controlled.
- Osteoporosis. bisphosphonatemedications to improve bone density.
- Gallstones andbile duct stones. A health care provider may use surgery to
remove gallstones. He or she may use endoscopic retrograde
cholangiopancreatography, which uses balloons and basketlike devices, to
retrieve the bile duct stones.
- Liver cancer. A health care provider may recommend screening tests every
6 to 12 months to check for signs of liver cancer. He or she may treat cancer
with a combination of surgery, radiation, and chemotherapy.
- When is a liver transplant consideredfor primary biliary cirrhosis?
A health care provider may consider a liver transplant when cirrhosis leads
to liver failure or treatment for complications is ineffective. Liver
transplantation is surgery to remove a diseased or an injured liver and
replace it with a healthy liver or part of a liver from another person, called a
donor.

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What lifestyle changes may be helpful for PBC patients?
 A reduced sodium diet , Drinking ample water , Taking calcium and Vitamin
D supplements , Avoiding or reducing the consumption of alcohol ,
Reducing stress , Exercising, particularly walking , Skin Care , Regular
dental examinations , Artificial tears for dry eyes .