CHRONIC LIVER DISEASE presentation .pptx

cme houseman hpsf. chronic liver disease management in malysia

1. CHRONIC LIVER DISEASE Prepared by : Kow & Kamalia Supervised by : Dr Raymond

2. Definition Acute : progressive deterioration of liver function within 8 weeks from onset without pre existing liver disease Chronic : hepatic injury/ inflammation with/without fibrosis occuring in liver for more than 6 months

3. Pathogenesis

4. Etiologies of Chronic Liver Disease

5. Investigations

6. Staging Compensated OR Decompensated Patients with cirrhosis who have not developed major complications are classified as having compensated cirrhosis Patients who have developed complications of cirrhosis such as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome or hepatopulmonary syndrome are considered to have decompensated cirrhosis and have a worse prognosis.

7. CHILD-PUGH SCORE

8. Management outline ● Slowing or reversing the progression of liver disease ● Preventing superimposed insults to the liver ● Identifying medications that require dose adjustments or should be avoided entirely ● Preventing, identifying, and treating the complications of cirrhosis ● Determining the appropriateness and optimal timing for liver transplantation

9. Slowing or reversing the progression of liver disease Abstinence from alcohol substantially improves survival in alcoholic cirrhosis Usage of nonselective beta blockers in patients with compensated cirrhosis Antivirals therapy for viral hepatitis Immunosuppressant for autoimmune hepatitis

10. Preventing superimposed insults to the liver Vaccination against hepatitis A and B for those who are not already immune Influenza and pneumococcal vaccine

11. Preventing and identifying complications Variceal bleeding All patients with cirrhosis should undergo screening with OGDS so that prophylactic therapy can be given. Nonselective beta blocker or endoscopic variceal ligation Hepatocellular carcinoma Cirrhosis patients should undergo surveillance with ultrasonography every six months

12. Management of complications

13. Ascites Accumulation of fluid within perito cavity cavity 75% due to portal hypertension Massive ascites may also have hepatic hydrothorax, commonly on right side. Treatment sodium restriction <2g/day, fluid restriction (only in persistent hyponatremia), Diuretics : T. Spironolactone 100-200mg daily in divided doses, frusemide max 1g/day Paracentesis TIPS <50% pt with cirrhosis and ascites survive after 2years

14. Paracentesis Supplement 5 g of albumin per each liter over 5 L of ascitic fluid removed INDICATIONS: Diagnostic tap is used for the following: New-onset ascites - to determine etiology Suspected SBP Therapeutic tap is used for the following: Symptomatic ascites Refractory ascites Refractory ascites : despite max diuresis dose and compliance to salt restriction

15. Spontaneous Bacterial Peritonitis Spontaneous infection of ascitic fluid without intraabdominal source 30% seen in pt with cirrhosis and severe ascites. 25% in hospital mortality rate. Ssx : fever, abdominal pain/ tenderness and altered mental status Bacterial translocation from gut to lymph nodes eventually peritoneal seeding. Positive peritoneal c&s, peritoneal absolute neutrophil count >250/micro L. If more than 2 organisms, consider intraabdominal source. Risk can be reduced by diuresis since its concentrates ascitic fluid, raising ascitic fluid opsonic activity. - Suggest 2 weeks if blood culture positive. - Suggests repeat paracentesis after 48 hrs of cefotaxime. If PMNs <250/mm3 &ascitic fluid sterile, success with 5 days of treatment Prophylactic antibiotics aimed at decontaminating the gut (IV Cefotaxime 2g q8h (if life-threatening, q4h) for 5 days or IV Ceftriaxone 2g q24h for 5 days)

16. P atients who get SBP should get lifelong prophylaxis to prevent future episodes (40-70% risk of recurrence in 1 year) Lifelong prophylaxis T. Trimethoprim/Sulfamethoxazole 160/800mg for 5 days/wk OR T. Ciprofloxacin 750mg/ week

17. Variceal bleeding IV Ciprofloxacin 400mg q12h for 7 days or IV Ceftriaxone 1 g q24h for maximum of 7 days All patients with cirrhosis and UGIB should receive prophylaxis for 7 days (50% develop SBP after bleed) Non bleeding varices Trimethoprim/Sulfamethoxazole 160/800mg PO daily for 7 days

18. Hepatorenal syndrome Functional renal f ailure without renal pathology in 40% of pt with advance cirrhosis/ acute liver failure. usually represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. Type 2 has better outcome. Treatment : Midodrine Octreotide Iv albumin

19. Hepatopulmonary syndrome Blood vessels in lungs dilate until lungs loses ability to transfer oxygen. 5-32% of pt with cirhosis develop HPS. Featured by SOB, low blood O2 level, cyanosis and clubbing. Treatment : symptomatic and ultimately liver transplantation. Lungs revert to normal within 1 year post transplantation.

20. Malnutrition Liver regulates protein and energy metabolism. Cirrhotic pt is more catabolic thus muscle protein is metabolized. Dietary supplement is necessary. In hepatic encephalopathy, need to monitor protein intake.

21. Coagulation abnormalities Reduced synthesis of clotting factors Impaired clearance of anticoagulants Hypersplenism Parenteral vitamin K doesn 't improve clotting factors on pt in view of synthesis of vitamin K dependent clotting factors diminished.

22. Bone disease Osteoporosis Due to malabsorption of vitamin D and reduced in calcium ingestion Catabolic state ➡ rate of bone resorption more than formation DEXA scan Treat with bisphosphonates *T. Alendronate sodium 70mg/week.

23. Hepatic encephalopathy spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of brain disease. diversion of portal blood into the systemic circulation. gut derived neurotoxins → brain Precipitants : Constipation, h igh protein load GI bleed Alkalosis, hypokalemia Sedatives Infection Mx : correct u/l precipitating factor, avoid sedatives, dietary protein restriction, lactulose L Lactulose cause colonic acidification → catharsis → eliminated nitrogenous products in gut. Goal : 2-3 soft stools /day. Alternative : Neomycin Metronidazole Rifaximin 550mg BD Zinc supplement

24. Liver transplantation Definitive treatment for patients with decompensated cirrhosis. Consider referral to hepatologist or liver transplant center for patients with MELD Score ≥10.

25. Post op comp lications

26. Facts from NATIONAL TRANSPLANT REGISTRY 2014 Prior to year 2000 most of the transplants were done in Sime Darby Medical Centre. In 2000 Selayang Hospital was built as a Government tertiary liver centre. In 2002 Selayang carried out its first liver transplant. 137 liver transplantations reported to the Registry between 1993 and 2014; Mean age of all transplant patients was 8.9 months to 74 yrs; 54% were male, 50% Chinese, 37% Malay, 10% Indian, 58% were for biliary atresia. Majority were living donor liver transplantations (58%). At the time of transplantation the main immunosuppressive drugs used were tacrolimus (88%) and steroids (64%). Transplant patient survival rate for the cohort 1993 to 2014 was 71% at 1 year, 66% at 5 years and 58% at 10 years.

27. C irrhosis with its different causes

28. Chronic Hepatitis B and C cirrhosis 80% of hepatitis C pt develop chronic hepatitis C. 20-30% of these pt will develop cirrhosis over 20-30years. 5% of hepatitis B pt will develop chronic hepatitis B. 20% of these pt will develop cirrhosis. HCV RNA, HCV genotype analysis HBsAg, anti HBs, HBeAg, anti HBE, HBV DNA viral load Antivirals Hep B ➡ Lamivudine/ Adefovir, telbivudine, entecavir,tenofovir Hep C ➡ pegylated interferon, ribavirin (SE : )

29. Alcoholic cirrhosis Chronic liver disease is 10th most common cause of death and 40% of it is due to alcoholic cirrhosis. Alcohol metabolism produces acetaldehyde . Pt with decompensated cirrhosis who continues d rinking alcohol has <50% 5years survival rate. Acetaminophen can still be used in liver disease pt as long as it is <2g /day.

30. Other treatment options : TNF alfa inhibitors → infliximab, etanercept Acamprosate to reduce alcohol craving Scores above 32 typically suggest poor prognosis and that these patients may be helped by steroid administration.

31. Autoimmune and NAFLD cirrhosis AUTOIMMINE HEPATIC CIRRHOSIS Usually pt with autoimmune hepatitis (AIH) presented with established cirrhosis. Mainstay of treat ment for AIH is corticosteroid and immunosuppressants Requires positive ANA/ aSMA for diagnosis NAFLD CIRRHOSIS With epidemic of obesity, more and more pt identified with NAFLD. Management of complications of cirrhosis in these is similar to other forms of cirrhosis.

32. NAFLD management

33. Biliary cirrhosis Intrahepatic and extrahepatic types. Different approach. Major causes are Primary Biliary Cirrhosis, Autoimmune Cholangitis, Primary Sclerosing Cholangitis and idiopathic adulthood ductopenia. Primary Biliary Cirrhosis [small & medium size bile ducts] 100 - 200 per million, females, 50years old Unkown cause. Cholestatic features with progressive liver cirrhosis. AMA presents in 90% of cases. Unique features : hyperpigmentation, Xanthelasma, xanthoma. Liver biopsy is most important for AMA negative pt. Treatment : C. ursodeoxycholic acid 13-15mg/kg/day Cholestyramine Plasmapheresis (severe intractable pruritus)

34. Primary sclerosing cholangitis [entire biliary tree] Unkown cause. To establish diagnosis, must involve biliary tree imaging → MRCP pANCA is positive in 65% of pt. >50% also have ulcerative colitis → colonoscopy. Most dreaded complication → cholangiocarcinoma. Treatment : PBC dosages of UDCA

35. CARDIAC CIRRHOSIS Definition : pt with long standing RHF may develop cardiac cirrhosis Elevated venous pressure → enlarged and swollen liver → poor circulation → fibrosis Treatment based on underlying cardiac disease. INHERITED METABOLIC LIVER DISEASE Hemochromatosis Disorder of iron metabolism→increased in hepatic iron deposition High level of transferrin and ferritin Regular therapeutic phlebotomy

36. 2. Wilsons disease Failure to excrete excess amount of copper Low ceruloplasmin level, Kayser Fleischer ring Treat with copper chelating medications. 3. Alpha antitrypsin deficiency Abnormal folding of alpha AT protein → failure of its secretion from liver Diagnosis by alpha AT protein level and phenotyping. 4. Cystic fibrosis Biliary type cirrhosis can occur and pt derive benefit from chronic use of UDCA.

37. Pregnancy and liver cirrhosis[multidisciplinary approach] Consultation key elements Effects of pregnancy Effects of disease Therapeutic options during gestation & potential teratogenicity Expected complications and its management MELD score < 6= good outcome MELD > 10= poor prognosis Preconception Assisted reproductive technology Counselling Nutritional supplement Conception outcome 58% live births 19% miscarriage 15% terminated 6% stillbirths Fetal outcome 18% born before 30weeks 64% born before 37weeks Risk of IUGR High rate of caesarean section Maternal outcome 7.8% maternal mortality. 78% of it d/t variceal haemorrhage. May becomes decompensated during pregnancy

38. References Harrisons 19th edition Davidson 22th edition CPG acute variceal hemorrhage AASLD : https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/cld.415 Medscape Uptodate Researchgate Sciencedirect

39. JAUNDICE Def : yellowing of skin, sclera, mucosa from increase plasma bilirubin (visible >60 miromol/L) Classified Conjugated or unconjugated Pre hepatic or hepatocellular or cholestatic/obstructive

40. Classification of jaundice Unconjugated hyperbilirubinemia: Overproduction - hemolysis (malaria,DIC), ineffective erythropoiesis Impaired hepatic uptake - drug (pcm,rifampicin), ischemic hepatitis Impaired conjugation - syndrome (gilbert, crigler najjar) Physiological neonatal jaundice - combination of the above Conjugated hyperbilirubinemia Hepatocellular dysfunction (hepatocyte damage with some cholestasis) -viruses (hepatitis,cmv,ebv), drug, alcohol, cirrhosis, liver mets/abscess, hemochromatosis, autoimmune hepatitis, septicemia, leptospirosis, syphilis, alpha 1 antitrypsin def, budd chiari, wilson disease, Impaired hepatic excretion - cholangitis, drug, gallstone, pancreatic ca, compression of bile duct (cholangiocarcinoma, porta hepatis, choledochal cyst, caroli disease, mirizzi's syndrome

41. The pathway of bilirubin metabolism

42. History Blood transfusion Drug use Tattoo Sexual activity Travelling Alcohol use

43. Examine Sign of chronic liver disease Hepatic encephalopathy Lymphadenopathy Hepatomegaly Splenomegaly Ascites Palpable gallbladder

44. Test Urine - bilirubin absent in pre hepatic cause while urobilinogen is absent in obstructive jaundice Hemato : FBC, COAG, reticulocyte count, coomb’s test, haptoglobin for hemolysis, malaria parasite Chemistry : LFT, gamma GT Microbiology and serology : culture and sensitivity, infection screening USG : to look for dilatation bile duct, gallstone, liver mets, pancreatic mass ERCP/MRCP Liver biopsy CT/MRI - if suspected of malignancy