Chapter 4.2
Primary biliary cirrhosis and primary sclerosing cholangitis and nutrition
Natasha A. Vidas
King’s College Hospital NHS Foundation Trust, London, UK
Primary biliary cirrhosis (PBC) is marked by chronic progressive inflammation and destruction, predominantly of the small but also the medium-sized intrahepatic bile ducts. The destruction of the bile ducts leads to reduced bile flow from the liver into the GI tract, known as cholestasis. The consequent build-up of bile in the liver over time causes progressive inflammatory destruction of the hepatocytes leading to fibrosis, then cirrhosis and ultimately liver failure [1]. Patients with advanced PBC and cirrhosis may develop ascites, hepatic encephalopathy and portal hypertension. The latter may develop in patients before cirrhosis is established, in contrast to other liver diseases [2]. The pathogenesis is thought to be autoimmune with a complex interplay of environmental triggers such as bacteria and viruses, combined with a genetic predisposition [2].
Primary sclerosing cholangitis (PSC) is a chronic progressive disorder defined by inflammation, fibrosis and stricture formation of the whole biliary tree, both intra- and extrahepatic bile ducts, mostly medium and large bile ducts [3]. The hepatic injury that ensues is as for PBC; cirrhosis, portal hypertension and liver failure usually follow [4]. The pathogenesis is less clear but evidence suggests involvement of autoimmune, genetic and infectious factors [5].
4.2.1 Factors involved in causation
Fatigue is debilitating and affects quality of life and normal daily activities in PBC and PSC [6]. Tyrosine and tryptophan are involved in the pathogenesis of fatigue and Borg et al. (2005) found that patients with PBC and increased tyrosine concentrations had less fatigue [6]. However, further studies are required to evaluate the effect of tyrosine and tryptophan supplementation before recommendations can be made.
4.2.2 Nutritional consequences
Malnutrition
Malnutrition has been reported in patients with PBC with and without established cirrhosis [7,8] and in most patients with cirrhosis irrespective of disease aetiology, including PSC [9,10]. Contributing factors include reduced oral intake, particularly in patients with ascites, fat malabsorption and increased metabolic rate. The latter has been found to increase as liver disease progresses [11].
Metabolic bone disease in liver disease (hepatic osteodystrophy)
Hepatic osteodystrophy, seen predominantly in cholestatic liver disease but also in other chronic liver diseases, includes osteoporosis, the dominant form of hepatic bone disease [12], and osteomalacia, which is more frequent in severe malabsorption and advanced liver disease [13]. Both may affect quality of life and morbidity [13]. Osteoporosis has been found to increase with worsening liver disease in both PBC and PSC [14]. The reported incidence of osteoporosis is 30% in PBC [2] and 4–10% in PSC [15]. The pathogenesis of this disorder is complex and multifactorial [13]. Suggested causes in PBC include raised bilirubin inhibiting osteoblast function; increased bone resorption; deficiencies of calcium, magnesium, vitamin D and vitamin K; reduced muscle mass; increased duration of cholestasis; and medication side-effects (e.g. corticosteroids and cholestyramine that are sometimes used to treat the disease process) [13,16,17]. The causes of osteoporosis in PSC are similar to those in PBC [14].
Biochemical indices frequently guide treatment of osteomalacia as bone biopsies used for diagnosis are invasive and thus not routinely used [13]. Osteomalacia particularly seen in PBC is associated with low concentrations of 25-hydroxyvitamin D. Contributing factors include vitamin D malabsorption corresponding to steatorrhoea; impaired dietary vitamin D intake; reduced exposure to ultraviolet rays; increased renal loss of soluble vitamin D; and reduced enterohepatic circulation of vitamin D [12,13,18]. Metabolism of vitamin D is normal in PBC [2,19], except in those with jaundice and clinically advanced disease [2]. The synthesis of vitamin D cutaneously in other jaundiced patients may also be impaired [14].
Malabsorption
Chronic cholestasis, frequently a consequence of PBC and PSC secondary to the disease process (i.e. the inflammation, fibrosis and destruction of the bile ducts) may lead to an inadequate biliary secretion of bile salts and hence a reduced ability to break down dietary fat [20]. The consequent malabsorption of dietary fat and fat-soluble vitamins (i.e. A, D, E and K) may lead to steatorrhoea. Weight loss and fat-soluble vitamin deficiencies may ensue. Steatorrhoea may also lead to calcium malabsorption secondary to the insoluble calcium soaps formed in the presence of unabsorbed dietary fat in the small intestine [20]. It is important to exclude and/or treat other causes of malabsorption and steatorrhoea, e.g. coeliac disease, ulcerative colitis (UC) and pancreatitis.
In PBC, 33.5%, 13.2%, 1.9% and 7.8% of patients have been found to have deficiencies of vitamins A, D, E and K, respectively [21]. In PSC deficiencies have been reported in 40%, 14% and 2% of patients for vitamins A, D and E respectively [22], with greater deficiencies found in patients undergoing pretransplant assessment: 82%, 57% and 43% for vitamins A, D and E respectively.
Hyperlipidaemia and xanthoma
In PBC serum lipids may be markedly elevated [2] though studies suggest there is no increased risk of cardiovascular disease. However, if there is a family history of lipid abnormalities or cardiovascular disease, treatment with cholesterol-lowering medication may need to be considered [2].
Disease symptoms
Symptoms of pruritus and fatigue in PBC and PSC and upper right quadrant pain (typically from bacterial overgrowth in the strictured bile ducts) in PSC usually develop when disease is quite advanced and can be severe and disabling. Ten percent to 15% of patients with PSC have intermittent episodes of cholangitis [4,23]. Functional status has been reported to be significantly reduced in patients with PBC [24]. Thus it seems reasonable to expect that nutritional status may be compromised secondary to symptoms of disease.
Medication side-effects
Cholestyramine used to treat pruritus can cause bloating, constipation and diarrhoea [2]. Antibiotics used to treat recurrent bacterial cholangitis in PSC long term may lead to diarrhoea [15] and possibly long-term nutritional consequences.
Co-existing autoimmune diseases
Coeliac disease has been found in 3–7% of patients with PBC and in 2–3% of patients with PSC [25]. Inflammatory bowel disease has been found in less than 5% of patients with PBC [19] and 60–80% of patients with PSC, with 48–86% of those having UC [15]. Pouchitis after colectomy and ileo-anal pouch formation is more common in PSC patients with UC than in patients with only UC – 60% and 15% respectively [3]. Both diseases, and the surgical consequences thereof, need to be taken into account in the nutritional management of these patients.
4.2.3 Dietary management
Since PBC and PSC are progressive diseases, monitoring patients over the course of their disease is important, particularly since metabolic rates, fat-soluble deficiencies, osteoporosis and osteomalacia have been shown to increase as disease severity increases. Disease symptoms of both PBC and PSC, medication side-effects, co-existing autoimmune diseases and the potential progression to cirrhosis should all be considered in nutritional assessment and intervention.
The advice for cirrhotic PBC and PSC patients is the same as that for other cirrhotic patients, i.e. regular meals and snacks, including a bedtime snack containing 50g of carbohydrate, to prevent protein catabolism and the latter to promote nitrogen balance [26,27]. The ESPEN 2006 guidelines for energy and protein requirements are used in clinical practice. All patients with inadequate oral intakes and/or weight loss should be encouraged to make high-energy, high-protein meal and snack choices to aid meeting their estimated requirements. Consider oral nutritional supplements and/or enteral tube feeding (ETF) if estimated requirements cannot be achieved orally.
Fat restriction
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