Copyright ©The Author(s) 2015.
World J Hepatol. May 8, 2015; 7(7): 926-941
Published online May 8, 2015. doi: 10.4254/wjh.v7.i7.926
Table 1 Primary biliary cirrhosis - autoimmune hepatitis overlap can present in the following ways
Immunoserological overlap: e.g., positive ANA/anti-smooth muscle antibody titers and elevated IgG in conjunction with AMA-positive PBC; or AMA positivity in AIH
Biochemical overlap: AST/ALT > 5 times upper limit of normal in patients with PBC or PSC; or AP > 3 times upper limit of normal in patients with AIH (or GGT > 5 times upper limit of normal in children)
Radiological overlap: clinical features of AIH with cholangiographic abnormalities indicative of inflammatory cholangiopathy; cholangiographic features of primary sclerosing cholangitis are randomly distributed annular strictures out of proportion to upstream dilatation[33]
Histological overlap: lymphoplasmacytic infiltrate and interface hepatitis on liver biopsy with bile duct lesions indicative of either PBC or PSC
Varying combinations of the above, including sequential presentations
Table 2 Clinical features of primary biliary cirrhosis
Clinical featuresPrevalenceMechanism
Fatigue20%-85%[55,56,58]Excessive manganese deposits in globus pallidum, elevated inflammatory cytokines
Pruritus20%-75%[35,58]Cholestasis, increased opiodergic tone
Xanthomas15%-50%[58]Hypercholesterolemia and hyperlipidemia[56]
Osteoporosis35%[59]Disturbances in bone remodeling due to metabolic changes in PBC
Dyslipidemia> 75%[60]Reduction in biliary secretion of cholesterol. Toxic effects of unconjugated bilirubin
Table 3 Drug therapy for primary biliary cirrhosis
DrugMechanism(s) of actionAdverse effects
Ursodeoxycholic acidProtection of cholangiocytes, stimulation of biliary secretions of bile acidsDiarrhea, hepatic decompensation (rare)
CorticosteroidsAnti-inflammatory, especially useful for interface hepatitisCataracts, hyperglycemia, osteoporosis, immunosuppression, poor wound healing, weight gain
BudesonideAnti-inflammatory, especially useful for interface hepatitisNausea, dyspepsia; systemic toxicity is much less than for other corticosteroids[73]
Obeticholic acidReduces bile acid synthesis, downregulates bile acid uptake proteinsPruritus
FibratesActivates peroxisome proliferator-activated receptorsMyalgias, rhabdomyalysis, elevated liver enzymes[72]
Table 4 Drugs without efficacy in primary biliary cirrhosis as demonstrated in clinical trials
Mycophenolate mofetil[111]
Table 5 Complications of cirrhosis or portal hypertension in patients with primary biliary cirrhosis
ComplicationSpecial considerations in PBCRef.
HepatomaLike other cirrhotics, patients with PBC have increased risk of developing hepatomas[189,203-205]
In patients with PBC who have not undergone a liver biopsy to document the diagnosis of cirrhosis, hepatoma screening should be initiated when the Mayo score > 4.1[126]
Surveillance for hepatoma in patients with cirrhosis from PBC should be performed every six months by abdominal ultrasound or an alternative modality of abdominal imaging[206]
Spontaneous bacterial peritonitisDiagnosed by abdominal paracentesis revealing > 250 polymorphonuclear leukocytes/mm3 in ascitic fluid[207]
Treated with a short course of multiple antibiotics, generally including either a third-generation cephalosporin or flouroquinolones[208]
Hepatic encephalopathyDiagnosed clinically by confusion, delirium, or stupor on physical examination, depending on degree of hepatic encephalopathy; possible presence of asterixis on physical examination; and elevated serum ammonia level in a cirrhotic patient[209]
Treatment options include rifaximin, lactulose, supportive care, and reversal of underlying precipitating causes, such as dehydration, infection, or gastrointestinal bleeding[209-211]
HRSType 1 HRS defined as doubling of serum creatinine level, reaching a level > 2.5 mg/dL in < 2 wk. Type 2 HRS defined as a less severely elevated serum creatinine level. Must exclude other causes of renal failure, especially hypovolemia in both types of HRS[212,213]
Treatment includes avoidance of nephrotoxic medications; short-term trial of volume expansion; and administration of vasopressin analogues, such as terlipressin, and α-adrenergic agonists, such as norepinephrine or midodrine. Ultimate treatment for type 1 HRS refractory to therapy is liver transplantation[213-215]
Esophageal varicesUsually occur only after Mayo score becomes > 4.1. Patients with advanced PBC can develop portal hypertension before developing established cirrhosis from nodular regenerative hyperplasia[216-220]
Esophageal varices usually diagnosed and graded by esophagogastroduodenoscopy
Specific therapies for esophageal varices include: endoscopic banding, endoscopic injection therapy, and non-selective beta-blockers. Transjugular intrahepatic shunt is recommended for refractory variceal bleeding, especially when the MELD score < 18[221,222]