Primary biliary cirrhosisد.خلدون ذنون-المرحلة الرابعة-الطب الباطني
Chronic progressive cholestatic liver disease of unknown cause.
Middle aged women are mainly affected. Female:male ratio 9:1.
Common in north Europe and north America, rare in Asia and Africa.
PathophysiologyImmune mechanisms involved.
Associated with other autoimmune diseases e.g thyroid
Granuloma formation with lymphocytes accumulation damage interlobular biliary ducts, result in fibrosis and cirrhosis.
Clinical featuresLethargy and arthralgia are common nonspecific features.
Pruritus is the most common initial complaint and may precede jaundice by months or years.scratch marks.
Jaundice is rare and late presenting feature.
Right upper abdominal discomfort but no fever or rigor.
Bone pain and fractures are due to osteomalacia and osteoporosis.
Weight loss later on.
Xanthelasma occurs in minority around eyes, hand creases, elbow, knee and buttocks.
Later on liver failure
Associated with sicca syndrome, systemic sclerosis, celiac disease, thyroid disease(hypothyroidism).
DiagnosisAntimitochodrial antibodies (AMA) present in 95% of patients.
Antismooth muscle antibodies present in 15% of patients.
Increased serum immunoglobulins (IgM).
Liver function test: cholestatic pattern.
Sonogram, MRCP, ERCP to exlude biliary obstruction.
Liver biopsy done in selected cases who test negative for AMA.
ManagementIf patient asymptomatic monitor every year.
Immunosuppressants: steroids, azathioprine, penicillamine, and ciclosporin are not effective.
Ursodeoxycholic acid (UDCA) improves liver function tests, and may slow down histological progression and it is widely used.
Pruritis: cholestyramine (anion binding resin) 4-16 gm/day ( powder mixed with orange juice taken before and after breakfast). Rifampicin and opioid antagonist (naltrexone) are alternative drugs. In resistant cases plasmapheresis and liver support device may benefit.
Fatigue which affect 1/3 of patients, no effective treatment, exclude depression and hypothyroidism.
Malabsorption: replace fat soluble vitamins, treat steatorrhea, exclude celiac disease.
Bone disease: measure bone density, treat osteomalacia and osteoporosis, replace calcium and vitamin D3, bisphosphonates for osteoporosis.
Liver transplant: indicated in liver failure and intractable pruritis. 5 year survival is 80%. Disease may recur in the transplant.
Pregnancy and the liverBefore you diagnose pregnancy related liver diseases exclude intercurrent and pre-existing liver diseases.e.g viral hepatitis and drug use.
Hepatitis A does not affect the fetus.
Hepatitis B affects the mother and the fetus. Perinatal vaccination and immunoglobulins are effective and protect the fetus.
Maternal transmission of hepatitis C occurs in 1% of cases.
Hepatitis E may more commonly progress to acute liver failure.
Pregnancy may worsen or improve autoimmune hepatitis.
Cirrhosis often leads to infertility
Gall stones are more common during pregnancy.ERCP to remove stones can safely be performed but lead protection of the fetus is needed. Ultrasound and MRCP are safe.
ALT and albumin fall during pregnancy but ALP increases (from placenta).
Use amiloride to treat ascites during pregnancy rather than spironolactone.
Continue use of penicillamine and azathioprine during pregnancy.
Pregnancy related liver diseases occur only during pregnancy and may recur during subsequent pregnancies and resolve after delivery. It occurs mainly in the third trimester.
Intrahepatic cholestasis of pregnancyResponsible for 20% of jaundice during pregnancy.
Mainly in the third trimester of pregnancy.
Associated with intrauterine growth retardation and premature labour.
Itching and cholestatic LVTs. Bilirubin may be normal.
Bile salts increase the serum.
Resolve after delivery
UDCA effectively controls itching
Recurs in 60% of subsequent pregnancies.
Acute fatty liver of pregnancyMore common in twin and first pregnancy.
Typically presents between 31-38 week of pregnancy.
Vomiting and abdominal pain followed by jaundice.
Complications : lactic acidosis, coagulopathy, encephalopathy, renal failure, hypoglycemia.
It is due to defect of fatty acids in mitochondria leading to microvesicular fatty liver, some women have genetic mutations.
Similar conditions (hepatic mitochondrial cytopathies) are due to: sodium valproate, tetracyclines, Reyes syndrome (aspirin use in child), bacillus cereus toxin.
Exclude toxaemia of pregnancy which is more common and is associated with high serum uric acid and hemolysis.
Management: early diagnosis and delivery.
Toxaemia of pregnancy and HELLPHELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a variant of pre-eclampsia.
Affects multiparous women.
Occurs between 27-36 weeks of pregnancy.
Hypertension, proteinuria, edema, jaundice in 5%.
Low HB,fragmented RBC, marked increase in serum transaminases, raised D-dimer.
Hepatic infarction and rupture.
DIC, placental abruption.
Maternal mortality 1%, perinatal mortality up to 30%.
Delivery results in prompt resolution.
Recur s in 5% of future pregnancies.
Liver transplantationIndicated in: acute liver failure, metabolic diseases, hepatic cancer and in all causes of liver cirrhosis (71%)
Indications in cirrhosis:
First episode of bacterial peritonitis
Recurrent variceal hemorrhage
Persistent hepatic encephalopathy
Child-pugh C and MELD score>12.
Contraindications: sepsis, extrahepatic malignancy, active alcohol and substance misuse, marked cardiopulmonary disease.
Patients need ABO and size matched donors. HLA matching is not needed.
Immunosuppressive drugs after transplant: tacrolimus, ciclosporin, prednisolone, azathioprine and mycophenolate.
Types of liver transplant: two types
Split liver transplant: cadaveric liver used, large right lobe for adults and small left lobe for child.
Living donor transplantation: left lateral segment or right lobe.
Donor mortality is 0.5-1%.
Acute rejection: in 60% occurs in the first 6 weeks. It responds to 3 days of high dose prednisolone.
Surgical complications: hepatic artery thrombosis, biliary stricture, portal vein thrombosis.
Infections: CMV virus e.g hepatitis. Tuberculosis.
Late complications: disease recurrence in the graft, chronic vascular rejection is rare.
Drug complications e.g ciclosporin causes renal dysfunction.
Prognosis: worse for acute liver failure than chronic. Generally 1- year survival is 65%, at 5-years 59%. In cirrhosis 1-year survival is 85% and 5-year survival is 75%.