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Written by Dr Sebastian Zeki
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Metabolic bone disease in PBC This is related to the duration and severity of PBC and to the intensity and duration of jaundice. The aetiology is of “Low-turnover" osteoporosis (bone formation is inhibited by cholestasis action on osteoblasts) and bone resorption is low or normal. Vitamin D levels are usually normal. Refer for OLT Not better- discontinue MTX Further rpt liver bx worse If rpt LFT’s normal, continue UDCA for 16m then do liver Bx If repeat LFTs abnormal or rpt liver bx abnormal, then add colchicine for 12 m Rpt liver bx
UDCA (+?colchicine/ +?MTX) Portal hypertension/ jaundice Stage IV
UDCA for 6m
Stage I/II/III
Liver biopsy
Liver transplantation
Naloxone (first infusion and then oral naltrexone Phenobarbital
Rifampicin
+Methotrexate
+Colchicine
UDCA
PBC- T reatment UDCA -It improves LFT’s and reduces disease progression and possibly transplant-free survival. - It doesn’t relieve fatigue and pruritus. It is more effective in patients with early disease. Cirrhotics do not benefit from UDCA. Additional therapy is probably needed in patients with florid bile duct lesions and severe lymphocytic piecemeal necrosis and lobular inflamm - tion since these patients appear to be at increased risk for disease progression despite UDCA. Treatments: -Vitamin D supplemention- not useful unless the patient is deficient. -Calcium supplementation (at least 1500 mg/day)-especially post liver transplant. -Oestrogen therapy- in postmenopausal women with PBC this may be useful but not routinely recommended and not transdermal (first-pass hepatic metabolism). -Standard osteoporosis management applies. For severe symptomatic, refractory bone disease patients should be referred for a liver transplanta - tion (bone loss is accelerated 3-4 months after transplantation). Osteomalacia- Rare- this is due to vitamin D deficiency and fat malabsorption. Bile acids
UDCA
Bile acids
UDCA decreases plasma and biliary endogenous [bile acid] possibly by competing for uptake or encouraging hepatic clearance of bile acids The endogenous bile acids have greater deter - gent activity and are therefore more hepatocyte toxic than UDCA. HLA I and II
UDCA (or one of its metabolic conjugates) may decrease immune-mediated destruc - tion of hepatocytes (decreases the expression of HLA class I and II antigens) UDCA inhibits eosinophil activa - tion and degranula - tion. Mechanism of action of UDCA — UDCA does not appear to influence the prevalence of florid bile duct lesions, suggest - ing that it exerts its beneficial effects by protec - ing against the consequence of bile duct destruc - tion rather than preventing it. Liver transplantation in primary biliary cirrhosis The Mayo model is most widely used Optimal time for transplantation When 6m survival is < 80 %. (MELD or Mayo score) Transplantation Indications: In addition to Mayo score Plasma [bilirubin] > 5 mg/dL and increasing Serum [albumin] < 2.8 g/dL (28 g/L) and decreasing Signs of decompensation or portal hypertension Intractable pruritus Recurrent, debilitating nontraumatic bone fractures Outcome after liver transplantation -1y- survival 95 % Effect of transplantation on symptoms: Resolution rates vary. Pruritus/ complications of end-stage liver disease, resolve quickly Jaundice and ascites: days to months. Splenomegaly usually persists although the enlarged spleen may decrease slightly in size. Skin xanthomas also resolve within a few weeks. Hepatic osteodystrophy 12-18m PBC Recurrence in the transplant - 22 % after 10 years. Risk factors For Recurrence Older recipient age Longer cold ischemia time Treatment with tacrolimus (compared with cyclosporine) Younger donor age. Treatment UDCA (effect on the natural history of recurrent PBC is uncertain) 1. Malabsorption ADEK supplementaion 2. Lipid lowering - no need 3. UDCA 4. Liver transplantation = 50% 5 year survival 5. Monitoring = 6/12 alpha fetoprotein + USS 6. Azathioprine/steroids - marginal improvement 7. For pruritis...(see section on pruritis in liver disease) 8. For fatigue If severe, treat with modafinil (narcolepsy drug) 9. Osteoporosis Pruritis in PBC
