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Cirrhosis and complications

Cirrhosis and complications. Cengiz Pata Gastroenterology Department Yeditepe University. Overview. 1) Criteria for Referral for Transplantation 2) Varices 3) Ascites/TIPS 4) S.B.P. 5) Encephalopathy 6) Hepatorenal Syndrome 7) Hepatocellular Carcinoma. Etiology.

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Cirrhosis and complications

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  1. Cirrhosis and complications Cengiz Pata Gastroenterology DepartmentYeditepe University

  2. Overview 1) Criteria for Referral for Transplantation 2) Varices 3) Ascites/TIPS 4) S.B.P. 5) Encephalopathy 6) Hepatorenal Syndrome 7) Hepatocellular Carcinoma

  3. Etiology • Enfections (HBV, HCV, HDV, HGV) • Hereditary disease (Wilson, Hemokromatozis, Alfa-1 antitripsin,tyrosinemia) • Toksic (alchol,drugs(Mtx) • İmmünologic (OİH) • Vasculer (corpulmonare, Budd Chiarry, Portal ven trombosis) • Bilier Disease (PBS, Cystic Fibrosis,Sarcoidosis,PSK,PFIK,SBS) • Malnutrision , Bypass surgery • İndian Child Age Disease • NAFLD

  4. Reasons for Liver Transplantation: U.S. Etiology%Disease from Hepatitis C 40 IDU 65%, BT 5%, others Alcohol 30 alcoholism PBC/PSC 10 congenital Hemochr <5 genetic HBV 5 vertical/horizontal Biliary atresia 30 congenital Metabolic d/o 20 congenital

  5. Fibrosis Progression: Hepatitis C Normal Liver Mild fibrosis Severe Fibrosis Cirrhosis Slide courtesy of Bennett, MD.



  8. How do we know if a patient has cirrhosis/ portal hypertension ? • Liver biopsy: Stage IV scarring • CT scan: hypertrophied L lobe, nodular contour, enlarged portal vein, splenomegaly, varices, ascites • Labs: low platelet count, elevated bilirubin, prolonged INR • Physical exam: spider angiomata, jaundice, splenomegaly, ascites, leg edema

  9. Timing of referral for consideration of liver transplant ? A: 5-6, B: 7-9, C: 10 or more Modification for Bilirubin in PBC/PSC: 1-4, 4-10, >10

  10. Timing of referral for consideration of liver transplant ? • Since February 2002, listing for transplantation is on the basis of a MELD score and a CPT score • MELD (Model for End-Stage Liver Disease): developed at Mayo Clinic as a separate “liver disease severity index” • MELD: 0.38xloge(bilirubin, mg/dl) + 1.12xloge(INR) + 0.96 xloge(creatinine, mg/dl) + 0.64x etiology Website: www.unos.org

  11. Implication for Transplant • Many of complications of cirrhosis were formerly considered reasons to “increase a patient’s status,” specifically: 1) Refractory variceal bleeding 2) Refractory hepatorenal syndrome 3) Refractory hepatic encephalopathy • were accepted as reasons to make patients on the list for transplant “2A,” and give them higher priority

  12. Treatment Recommendations- Cirrhosis Decompensated Compensated Hepatoma Surveillance U/S, AFP q 6 months Monitor Liver Function PT, Alb, Bili q 3-6 months Varices Surveillance Vaccination- in HCV, against HAV, HBV Variceal Bleed Ascites SBP Hepatorenal Synd. Encephalopathy Figure 1. Treatment Flow Sheet for Patients with Cirrhosis (Garcia-Tsao G, 2003)

  13. Variability in Natural History of Cirrhosis • Natural history is clearly variable based on: - ongoing alcohol consumption, leading to acute exacerbations in portal pressures, particularly increasing risk for variceal hemorrhage - relation between cirrhosis etiology and HCC (HBV>HCV>?NASH)

  14. Morbidity and Mortality in Compensated Cirrhosis Type C: A Retrospective Follow-up Study of 384 Patients Mean follow-up: 5 years Ascites Enc/J Fattovich G et al, Gastroenterology 1997;112:463

  15. Morbidity and Mortality in Compensated Cirrhosis Type C: A Retrospective Follow-up Study of 384 Patients • 26% of patients decompensated during follow-up (8% HCC, 18% other) • Odds of decompensation: 12% at 3 years, 18% at 5 years, 29% at 10 years • Probability of survival after decompensation: 50% at 5 years • Death: 51 (13%): roughly 1/3 HCC, 1/3 liver failure, 1/3 unrelated to cirrhosis Fattovich G et al, Gastroenterology 1997;112:463

  16. Effect of Hepatitis B and C Virus Infections on the Natural History of Compensated Cirrhosis: A Cohort Study of 297 Patients Median f/u: 6.5 years Fattovich G et al, Am J Gastro 2002;97:2886

  17. Effect of Hepatitis B and C Virus Infections on the Natural History of Compensated Cirrhosis: A Cohort Study of 297 Patients • HCV: 53% decompensated (17% HCC, 36% other) HBV: 34% decompensated (14% HCC, 20% other) • Probability of 5-year survival after decompensation: HBV 28%, HCV 47% • Death or liver transplant: 70 (22% of HBV, 26% of HCV) Fattovich G et al, Am J Gastro 2002;97:2886

  18. PROBABILITY OF DEVELOPING DECOMPENSATED CIRRHOSIS 257 patients with compensated cirrhosis number being followed Gines, Hepatology 1987. time in months

  19. Cirrhosis Natural History Studies Summary • No decompensation: 80% 10-year survival • Decompensation is variable, imperfectly predicted. Portal HTN vs. synthetic dysfunction • HCC, ascites: the 2 principal forms of decompensation • Risk of decompensation: roughly 4-5% per year in a patient with Child’s A cirrhosis • After decompensation, probability of 5-yr survival without transplant: 35-50%

  20. Time to disease progression DB treatment and off-treatment follow-up Percentage with disease progression 21% Placebo P=0.001 9% Lamivudine Time to disease progression (months) Placebo (n=215) ITT population Lamivudine (n=436) p=0.001

  21. Risks of Complications of Cirrhosis ?30+% HCC Death 1.5% 11% 2.5% Ascites Cirrhosis ?20+% 1.1% Variceal Bleeding 0.4% Liver Transplant percent per year Encephalopathy adapted from Bennett WG et al, Ann Intern Med 1997;127:855

  22. Median Survival Times in Cirrhosis • Compensated Cirrhosis 9 yrs • Decompensated Cirrhosis 1.6 yrs • Jaundice • Encephalopathy • Ascites • Variceal hemorrhage • SBP 9 mos • HRS type II 6 mos • HRS type I 2 wks

  23. Bleeding Varices

  24. Varices-Background • Management of acute or acutely-bleeding varices is accepted: a) IV octreotide b) band ligation > sclerotherapy for esophageal varices, TIPS placement (or attempts at glue injection at some sites) for acutely-bleeding gastric varices. 7 days of antibiotics recommended • Controversies: 1) Primary prophylaxis 2) Secondary prophylaxis

  25. Primary Prophylaxis- Varices • 15-25% of unselected cirrhotics screened endoscopically will have large or high-risk varices • Mortality of first variceal hemorrhage remains high, 20-35% D’Amico G et al, Hepatology 1995;22:332-54 • Fewer studies on prevalence of gastric varices in unselected cirrhotics; 4% ? Sarin S et al, Hepatology 1992;16:1343-49

  26. Prevention of FIRST Variceal HemorrhageMeta-Analysis (11 trials) D’Amico et al. Sem Liv Dis 1999

  27. Prediction of Large Varices • Platelet count, Child-Pugh class independent risk factors for the presence of any varices (plts <90K) and large varices (plts <80K) in 300 cirrhotics without prior bleeding being evaluated for OLT Zaman A et al, Arch Int Med 2001;161:2564-70

  28. Zaman et al, Arch Int Med 2001 Multivariate Predictors of Large Varices: Platelet count OR 2.3, p=.001 Child-Pugh class OR 2.75, p=.007

  29. Primary Prophylaxis • Beta-blockers reduce the incidence of first variceal hemorrhage compared to placebo Poynard T et al., NEJM 1991;324:1532-1538 • Band ligation may be more effective than Propranolol in high risk patients Sarin S et al, NEJM 1999;340:988-93

  30. Primary Prophylaxis of Varices: An algorithm • It is reasonable to perform endoscopic screening in all cirrhotics (stable, willing to be tx’d); it should likely be performed in all Child’s C cirrhotics • Beta blockade (Propranolol, Nadolol, goal HR 55-60) is the preferred approach; band ligation is an alternative for high risk varices or in patients who can’t tolerate Propranolol - not as many data in gastric varices nor portal gastropathy, but prophylaxis may be similar

  31. Secondary Prophylaxis of Varices • Variceal hemorrhage has a 2-year recurrence rate of 80% • Once acute bleeding has resolved, two large trials have found that beta-blockade and band ligation have similar efficacy in controlling rebleeding Minyana J et al, Hepatology 1999;30:215A Patch D et al, J Hepatology 2000;32:34

  32. Secondary Prophylaxis of Varices • Banding sessions are typically repeated at 7-14-day intervals until obliteration, typically 2-4 sessions • TIPS vs endoscopic tx: rebleeding less with TIPS, but worse encephalopathy, no change in mortality Papatheodoridis GV, Hepatology 1999;30:612-22 • Beta-blockers or banding are first-line

  33. Hepatic encephalopathy • GIS bleeding • Enfection • higher protein • diuresis • constipation • Elektrolit inbalance • Dehidratation • Sedative • Hepatik injury • Portasistemic shunt

  34. Hepatic encephalopathy • Liver failure, failure of CNS • 1 year survive %40 • NH3, Glutamine,katekolamine, serotonine,GABA

  35. Stages of Hepatic encephalopathy 0-1 : psychometric tests slow • : abnormal sleep, dyscordination • : lethargy, ataxia, disarthria,behavirol dysinhibition, asterix, poor tests • :confusion, delirium, semi stupor, incontinence, disorientation, amnesia, rigidity, paranoia, abnormal reflex, nistagmus, babinski • : coma, no cognition, no behavior, decortica or decerebrate, dilated pupils

  36. Hepatic encephalopathy Treatment • General support • Treatment of etiologic factor • Medical : Lactulose, antibiotic (neomycin,metronidazole) Flumazenil • Transplantation

  37. HRS • impaired renal function • İmpaired arteriel circulation • Renal vazoconstruction • GFR↓ • No pathologic lesion • 1 mounths survival %95 • %7-15 • Type 1:weeks, agrrevation important ( diuretic, parasenthesis, SBP..) • Type 2 : mounths, better prognose

  38. Hepatorenal Syndrome • 2 types: Type I: rapid development of renal dysfunction (Cr rising to >2.5mg/dl in 2 weeks): median survival 2 weeks Type II: slower rise, Cr >1.5mg/dl • Management: 1) Ensure Diagnosis 2) Liver Transplantation

  39. HRS • Major Criteria GFR low (cre1.5mg/dl↑ or Cre clirence 40↓) No shock, nefrotocsic drug, enfection or loss of fluid Good function after stoping diuretic and 1,5 lt saline No paranchymal disease or nefrolithiasis on US 500mg/d↓/day proteinuri • Minor Criteria Urine volume 500↓ Urine Na 10 mEg/L↓ Higher urine osmolarite than plasma Serum Na 130 mEg/L↓ 50 red cell↓ urine

  40. HRS • Dopamine • Mizoprostole • Vazopressine (Orlipressin,terlipressin) • TIPS • MARS • Transplantation

  41. TERLIPRESSIN+ ALBUMIN IN HRS Uriz J Hepatol 2000;33:43-18

  42. EXTRACORPOREAL ALBUMIN DIALYSIS MARS U Heemann et al. Hepatology 2002; 36: 949-958

  43. Natural History of Cirrhosis in 2005: Altered by What We Do • More aggressive screening, for varices, HCC will mean problems are identified earlier • Ablative therapies for HCC • Obliteration of varices/ beta-blockade • TIPS • Liver Transplantation

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