CHRONIC LIVER DISEASE ksdh a presentation

Chronic Liver Disease

1. Azong Abdul-Wahid Akanlug -Ba Chronic Liver Disease

2. OUTLINE DEFINITION BRIEF ANATOMY AND PHYSIOLOGY OF THE LIVER AETIOLOGY CLINICAL BREAKDOWN INVESTIGATIONS APPROACH COMPLICATIONS MANAGEMENT PROGNOSIS CASE SCENARIO

3. DEFINITION Definition: persistent liver disease for more than 8 weeks Persistent hepatic injury, with or without clinical symptoms, resulting in progressive histological alterations Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.

4. CIRRHOSIS Definition: histological presence of bands of fibrous tissue that link central and portal areas and form parenchymal nodules, is a potential end stage of any acute or chronic liver dx Aetiological type Posthepatitic – after acute or chronic hepatitis Postnecrotic – after toxic injury May follow chronic biliary obstruction – biliary cirrhosis

5. CIRRHOSIS Morphological type Macronodular – nodules of various sizes up to 5cm separated by broad septa Micronodular – with nodules of uniform size <1cm separated by fine septa

6. BREIF ANATOMY AND PHYSIOLOGY OF THE LIVER

7. AETIOLOGY Major congenital disorders ; Biliary atresia, Idiopathic neonatal hepatitis, Tyrosinaemia ,Untreated galactosaemia , ETC Toxic : Alcohol ,Glucocorticoids, Amiodarone ,Tamoxifen, Antiretroviral agents, Tetracyline , Herbal preparations Autoimmune Hepatitis (AIH) ,Clinically indistinguishable . Infectious : Hepatitis A-E , EBV, CMV, Yellow Fever, Lues , Typhoid, Leptosp Others : Wilson disease, Cystic fibrosis, Non-alcoholic fatty liver disease

8. CLINICAL PRESENTATION Common signs and symptoms may stem from decreased hepatic synthetic function eg , coagulopathy, portal hypertension, hepatic encephalopathy. Jaundice Clubbing Itchiness Fatigue confusion Oedema Bleeding disorders such as epistaxis Palmer erythema Leuconychia Spider naevae Growth failure Infections Gynecomastia

9. CLINICAL PRESENTATION Portal hypertension causes may be Prehepatic eg . Portal vein thrombosis, splenic vein thrombosis Intrahepatic eg . Schistosomiasis, Cirrhosis, Veno-occlusive disease Posthepatic eg . Budd-Chiari syndrome (hepatomegaly, abdominal pain, ascites)

10. CLINICAL PRESENTATION Ascites is suggested by the following findings on physical examination: Abdominal distention Bulging flanks Shifting dullness Fluid thrill

11. INVESTIGATION These will depend to a considerable extent upon clinical suspicion of the aetiology . FBC: occult bleeding may produce anaemia; hypersplenism may cause thrombocytopenia LFTs: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, gamma- glutamyltransferase (gamma-GT), bilirubin, albumin, Coagulation profile

12. INVESTIGATION Renal function tests and electrolytes Ferritin: low ferritin may indicate iron deficiency from diet or blood loss; ferritin is raised in haemochromatosis. Viral antibody screen: to look for evidence of hepatitis B or C infection. Fasting glucose/insulin/triglycerides and uric acid levels: these should be measured if non-alcoholic steatohepatitis (NASH) is suspected.

13. INVESTIGATION Autoantibody screen: ANA, SMA, anti-LK microsomal, soluble liver Alpha-1-antitrypsin level: to assess for alpha-1-antitrypsin deficiency Ceruloplasmin and urinary copper: to look for Wilson's disease. Fasting transferrin saturation and HFE (haemochromatosis C282Y) mutation: along with a raised ferritin, these tests can screen for haemochromatosis. Urine for reducing sugars to look for Galactosaemia. If galactose positive check blood for GALT deficiency Fat soluble Vitamin levels in the blood

14. INVESTIGATION USG with doppler CT Scan MRI Liver biopsy Histology is usually needed for the definitive diagnosis of cirrhosis and liver biopsy is the gold standard. It may also give a clue to the underlying cause. If there are clear signs of cirrhosis, such as ascites, coagulopathy, and a shrunken nodular-appearing liver, then confirmation of diagnosis by biopsy may not be necessary.

15. Approach to the Patient Stepwise Assess for alcohol use Identify medications and supplements that can cause elevation of the LFT Test for viral hepatitis B and C Test for fatty liver

16. Prognosis in Cirrhosis Fibrosis Reversible in initial stages Cirrhosis Irreversible High susceptibility for complications Life expectancy markedly reduced Quality of life impaired

17. Child-Pugh Score A=5-6 (2 yr survival 85%) B=7-9 (2 yr survival 57%) C=10-15 (2 yr survival 35%) 1 2 3 Bilirubin <2 2-3 >3 Albumin >3.5 3.5-2.8 <2.8 INR <1.7 1.7-2.3 >2.3 Ascites Absent Mild-Moderate Severe / Refractory Encephalopathy Absent Mild (I-II) Severe (III-IV)

18. COMPLICATIONS OF CLD Definition: complications of CLD and cirrhosis are a consequence of the impaired metabolic and synthetic function and structural alterations of the parenchyma leading to elevated portal pressure.

19. COMPLICATIONS Growth faltering and malnutrition Hepatic encephalopathy Coagulopathy Hepatopulmonary syndrome Portal hypertension and variceal bleeding Ascites Spontaneous bacterial peritonitis Hepatorenal syndrome Hepatocellular carcinoma Endocrine dysfunction

20. MANAGEMENT OF CLD SUPPORTIVE Preventive therapy Malnutrition Fat soluble vitamin deficiency Variceal bleeding and coagulopathy Ascites Sepsis Nutritional support Psychosocial – both child and parents

21. NUTRITIONAL SUPPORT Modular feed High protein/CHO Balanced MCT/LCT Low salt 150% RDA Fat soluble vitamins A, D, E, K Route of feeding Oral Nasogastric Parenteral

22. Hepatic Encephalopathy 0 - Normal mental status, asterixis absent 1 – mild confusion, asterixis might be detected 2 - lethargy with inappropriate behaviour. Obvious asterixis 3 - Somnolent with incomprehensible speech and marked confusion 4 - coma HE is reversible! Treatment of precipitating causes (GIB, infection, dehydration, sedatives…) Lactulose (45-90g/dly) Enemas Protein restriction 0,8g/kg/day?? Antibiotics Liver Transplant

23. MANAGEMENT OF CLF – FLUID MGT Management of ascites Diagnosis: fluid thrill/shifting dullness, USG and abdominal paracentesis Fluid restriction Nutritional support

24. ASCITES AND FLUID RETENTION Fluid and salt restriction (2/3 maintenance) Diuretics: Spironolactone 2-3mg/kg/d up to 7mg/kg/d Furosemide 1-2 mg/kg or hydrochlorothiazide If resistant consider 5ml/kg 20% albumin infusion over 4-6h with furosemide Therapeutic paracentesis if ascites is resistant esp if compromising respiratory function Shunt – peritoneal-jugular or TIPSS Haemofiltration/Dialysis

25. MGT OF PRURITUS Enzyme inducers Phenobarbitone (5-15 mg/kg) Rifampicin (3 mg/kg) Bile diversion or Choleretics Ursodeoxycholic acid (20 mg/kg) Cholestyramine (1-4g/d) Biliary diversion Central Naloxone Ondansetron

26. MGT OF COAGULOPATHY Coagulopathy: Vitamin K 1mg/year to maximum of 5mg-10mg Fresh frozen plasma 10 ml/kg Cryoprecipitate Platelets Factor VII infusions or desmopressin Treat associated sepsis Anaemia: Oral iron Blood transfusion

27. SPECIFIC MGT Immunosuppression for Autoimmune hepatitis Penicillamine , Zinc, trientine for Wilsons Ursodeoxycholic acid for Cystic Fibrosis Anti-viral therapy for Hep B and C Diet Liver Transplantation

28. Treatment of alcoholic liver disease Abstinence Single most predictive factor for progression Can achieve improvement in fibrosis, reduction or normalisation of portal pressure, resolution of ascites.

29. SCHISTOSOMIASIS Caused by the deposition of Schistosoma  oocytes in presinusoidal portal venules Development of granulomata and portal fibrosis. Schistosomiasis is the most common noncirrhotic cause of variceal bleeding worldwide Schistosoma mansoni infection is described in Puerto Rico, Central and South America, the Middle East, and Africa.  S japonicum  is described in the Far East.  S hematobium,  observed in the Middle East and Africa, can produce portal fibrosis but more commonly is associated with urinary tract deposition of eggs.

30. PORTAL HYPERTENSION Results in Varices – oesophageal, gastric, rectal Portal gastropathy Hypersplenism Implications for a normal life School Contact sports

31. MGT OF PORTAL HYPERTENSION Medical Therapy UGI endoscopy - diagnostic and therapeutic Drug therapy – somatostatin analogues, Vasopressin propranolol Transjugular Intrahepatic Porto-systemic Shunt stent shunt (TIPS) Prophylaxis - propanolol

32. MGT OF ACUTE VARICEAL BLEEDING Resuscitation ABC IV access site of bleeding Stabilization Octreotide infusion Endoscopic – banding or sclerotherapy Baloon tamponade with Sengstaken-Blakemore tube if above unsuccessful Portosystemic shunt - TIPSS Liver transplantation

33. HEPATORENAL SYNDROME Definition: Functional renal failure in patients with severe liver disease Two types: I and II Pathophysiology –intense renal vasoconstriction with co-existent systemic vasodilation thereby reducing renal blood flow Diagnosis: by exclusion, rule out Hypovolaemic shock, nephrotoxic drugs or kidney dx Hereditary tyrosinaemia, Alagilles and polycystic kidney dx GFR is markedly reduced Treatment – heamofiltration, liver transplantation

34. ENDOCRINE DYSFUNCTION Regulation and function of multiple endocrine systems is affected in CLD Increased growth hormone resistance due to reduced synthesis IGF-1 and IGF-3 Feminization and hypogonadism in males – reduced testosterone and relative increase in oesterone and oestradiol Hypothyroidism – reduced T3 and T4

35. SPONTANEOUS BACTERIAL PERITONITIS Bacterial infection of ascitic fluid in the absence of secondary causes such as bowel perforation or intra-abdominal abscess Presentation – subtle with fever and irritability Diagnosis high index of suspicion Non-specific deterioration in condition Ascitic fluid for microscopy, culture (monomicrobial) PMN >250/mm cube is diagnostic Treat with antibiotics for 5-7days

36. PROGNOSIS OF CLD Depends on Aetiology Severity Progression to cirrhosis Portal hypertension Access to liver transplantation

37. CLIP Score Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000; 31:840 Child-Pugh A B 1 C 2 Tumor morphology Uninodular and extension 50% Multinodular and extension 50% 1 Massive or extension >50% 2 AFP <400 >400 1 Portal Vein Thrombosis No Yes 1

38. Survival curves based on the CLIP score Farinati, F, Rinaldi, M, Gianni, S, Naccarato. Cancer 2000; 89:2266.

39. INDICATIONS FOR TRANSPLANT Laboratory Indices Serum cholesterol <2.6 mmol/l (100 mg/dl) Indirect bilirubin >100 mmol /l (6mg/dl) Serum albumin <35 g/l (3.5 mg/dl) Prothrombin ratio (INR) >1.4 Portal vein reverse flow on ultrasonography

40. INDICATIONS FOR TRANSPLANT Clinical Severe portal hypertension Recurrent variceal bleeding Refractory ascites Intractable pruritus Growth retardation Unacceptable quality of life

41. REFERRAL OF CLD Early referral and recognition of liver disease Referral to Specialist Centre Early diagnosis Consideration of Treatment Improve outcomes for children

42. Case Senario 75 year old woman who HBsAg (+) HBeAg (+) ALT of 50 IU/L HBV DNA is 8000 copies/ mL. She has ascites and known esophageal varices.. Is she a Candidate for Liver Transplant??

43. THANK YOU