Notes by dr Claudio Italiano
Secondary biliary cirrhosis occurs in response to chronic biliary
obstruction from various causes. Neither the mechanism of fibrosis nor the
duration of the obstruction necessary to establish an irreversible fibrosis have
been established. However, in general, at least 6 months of obstruction is
required for cirrhosis to develop, even if minor time intervals have been
described.
Cholestasis can be intrahepatic or extrahepatic, the latter is also called "mechanical" cholestasis.
Primary sclerosing cholangitis is the most common cause of
intrahepatic cholestasis in addition to CBP. Cholestasis in this condition is
incomplete but progressive and leads to cirrhosis in many though not all
patients within 10 years. Patients with associated intestinal inflammatory
disease who have undergone intestinal resection may develop peristomal varices.
In cystic fibrosis, intrahepatic cholestasis with focal biliary cirrhosis may be
a complication of up to 25% of patients at the time of death, although liver
disease is often asymptomatic. The precyrrotic lesion is characterized by
biliary proliferation and ductal occlusion.
Cholestatic syndromes of childhood
and youth are often complicated by rapid progression to cirrhosis within 10-12
weeks of birth, even if they are readily recognized.
These disorders represent a
spectrum of pathological changes that often involve the atresia of both the
intra and extrahepatic ducts.
There is both clinical and histological overlap
with neonatal hepatitis. Fibrosis often progresses even after effective bile
duct decompression and normalization of bilirubin, with a biopsy appearance that
shows a picture similar to that of congenital hepatic fibrosis. Adult
extrahepatic cholestasis is more commonly the result of structural or mechanical
obstruction. Common lesions are choledocholithiasis, biliary or pancreatic
neoplasms, iatrogenic stenosis or chronic pancreatitis.
A type of
cholangiepatitis of Asians is characterized by intrahepatic bile-mud obstruction,
which can lead to recurrent cholangitis and secondary cirrhosis; the etiology is
unknown.
The progression of histological changes in chronic cholestasis has been well characterized. Degeneration of hepatocytes with formation of cellular rosettes and ductular proliferation can be followed by inflammatory biliary necrosis and early periductal fibrosis. Classical late aspects are the presence of thickened bile within the ductal lumen, the formation of bilious lakes and periductular biliary outbreaks. The early ductile alterations are reversible, but the persistent obstruction eventually leads to the formation of portal-center septa and the formation of nodules typical of irreversible fibrosis.
The clinical consequences of secondary biliary cirrhosis are initially those of
the underlying pathology. With the progression of the disease, jaundice becomes
the predominant symptom. Pruritus is of variable intensity. Lipid malabsorption
with steatorrhea and vitamin A, D, E and K deficiencies manifest in long-lasting
obstruction. Osteomalacia and osteoporosis can occur as a result of vitamin D
malabsorption and calcium deficiency. A disproportionate increase in hepatic
alkaline phosphatase (four to five times normal) compared to other liver
function tests is typical of secondary biliary cirrhosis. Other blood tests
typical of biliary damage can be similarly elevated, among them the y glutamyl
transpeptidase and the 5'-nucleotidase. The transaminases undergo lower
elevations of twice the norm. Hypercholesterolemia is frequent. Associated
markers of immune pathology or bacterial cholangitis may be present in patients
with sclerosing cholangitis or mechanical obstruction, respectively.
The foundation of therapy is the recognition and treatment of the underlying cause. In the case of extrahepatic obstruction, it is necessary to perform a biliary decompression or by biliary drainage or by the positioning of a biliary stent in case of neoplasia (neoplastic obstructive jaundice). Intrahepatic cholestasis is less easily passable than surgical drainage, for which management is limited to the treatment of complications. Pruritus can be controlled with cholestyramine (16-32 g / day to be administered in 2 doses) or, in the most severe cases, with opioid antagonists (eg, naloxone, nalmefene). Vitamin D and calcium supplement may be necessary in case of bone disease. Parenteral supplements of vitamins A, E and K are sometimes necessary. Regular exposure to sunlight increases the conversion of 7-dehydrocholesterol into vitamin D and may reduce osteomalacia. There is no single effective therapeutic medical agent for primary sclerosing cholangitis. For example, ursodeoxycholic acid improves biochemical parameters, but does not delay the progression of the disease; the future approaches could be with combined therapies (eg, ursodeoxycholic acid and methotrexate). Liver transplantation has high success rates in many patients with secondary biliary cirrhosis and liver function impairment.
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