The Liver for the Nonhepatologist

Transcription

1 The Liver for the Nonhepatologist Michael R. Charlton, MBBS, FRCP Hepatology Director and Medical Director of Liver Transplantation Intermountain Medical Center Salt Lake City, Utah FORMATTED: Chicago, IL: May 19, 2015 (INTRODUCTORY) Overview Slide 4 of 56 How do you diagnose cirrhosis? What is the natural history and prognosis of cirrhosis? Managing common complications Other issues - immunization, medications, etc in patients with cirrhosis Natural History of Chronic Liver Disease Old Paradigm Chronic liver disease 20+ years 5-10 years 1-5 years Compensated cirrhosis Development of complications: Variceal hemorrhage Ascites Encephalopathy Jaundice HCC Decompensated cirrhosis Slide 5 of 56 Death Chicago, IL: May 19, 2015 (INTRODUCTORY) 1

2 Natural History of Chronic Liver Disease New Paradigm Treated Untreated Slide 6 of 56 Frequency as indication (%) Slide 7 of 56 Longitudinal Trends in Frequency of Indications for Liver Transplantation ALD HBV NASH NASH + 50% CC CC PSC PBC AIH Charlton et al., Gastroenterology Data Source: SRTR Normal Cirrhosis Irregular surface Nodules Slide 10 of 56 Chicago, IL: May 19, 2015 (INTRODUCTORY) 2

3 Slide 11 of 56 Cirrhosis - Diagnosis Cirrhosis is a histological diagnosis However, in patients with chronic liver disease, various clinical, laboratory, and radiological features can suggest cirrhosis Diagnostic Algorithm Chronic liver disease and any of the following: Variceal hemorrhage Ascites Hepatic encephalopathy Yes No Yes Liver biopsy not necessary for the diagnosis of cirrhosis No Slide 12 of 56 Physical findings: Laboratory findings: Enlarged left hepatic lobe Thrombocytopenia Splenomegaly Impaired hepatic synthetic function Stigmata of chronic liver disease Yes No Radiological findings: Small nodular liver Intra-abdominal collaterals Ascites Splenomegaly MRE > 5 kpa Liver biopsy Staging fibrosis with NFS, FIB-4, and others High (>92%) NPV for advanced fibrosis Useful in clinical practice for excluding advanced fibrosis ELF performed only marginally better than NFS Modest PPV liver biopsy still necessary Slide 13 of 56 McPherson, Gut 2010 Guha, Hepatology 2008 Chicago, IL: May 19, 2015 (INTRODUCTORY) 3

4 Non-invasive measurement of hepatic fibrosis SERUM MARKERS FibroTest ELF Panel Fibromètre NAFLD fibrosis score Fibrometer Slide 14 of 56 TRANSIENT ELASTOGRAPHY biopredictive.com Biols.fr Transient Elastography Slide 15 of 56 Measures elasticity using sound waves Stiffness determined by multiple factors Degree of fibrosis Degree of inflammation- not good for acute hepatitis Degree of steatosis Not effective in morbidly obese patients >3.5cm Approved in U.S. 4/2013 now have XL probes J Gastrointestin Liver Dis Jun;17(2): Prediction of advanced fibrosis by transient elastography Slide 16 of 56 Wong, Hepatology 2010 Chicago, IL: May 19, 2015 (INTRODUCTORY) 4

5 Liver Stiffness (kpa) 0 Amplitude (mm) Gradient-Echo MRE 0 Amplitude (mm) Transient Elastography + ELF Algorithm Slide 17 of 56 Crespo, J Hepatol 2012 Active Driver Slide 18 of 56 MR Elastography of the Liver Phase Difference θ Plastic Tube Passive Driver Slide 19 of 56 Liver Stiffness Correlates With Fibrosis Stage Normal Yin et al. CGH 2007;5: < * < * < * Chronic Liver Disease (Fibrosis Stage) Kruskal Wallis Dunnett s Test α = 0.05 Chicago, IL: May 19, 2015 (INTRODUCTORY) 5

6 MRE Liver Stiffness Predicts Outcomes Slide 21 of 56 Asrani et al., Journal of Hepatology EPUB ahead of print Chicago, IL: May 19, 2015 (INTRODUCTORY) 6

7 Transient Elastography MRE Slide 23 of 56 Shear Stiffness (kpa) 0 5 Shear Stiffness (kpa) 1 0 Chicago, IL: May 19, 2015 (INTRODUCTORY) 7

8 2.9 kpa Clinical Interpretation of MRE Results 3.0 to 4.9 kpa No imaging features of cirrhosis 5 kpa Slide 24 of 56 Imaging features of cirrhosis Biopsy not required Biopsy required for staging Biopsy required for staging Biopsy not required Collagen Binding Peptide Gadolinium Chelation Slide 25 of 56 Slide 26 of 56 What Is the Natural History of Cirrhosis? Chicago, IL: May 19, 2015 (INTRODUCTORY) 8

9 Prognosis in Cirrhosis Compensated or Decompensated? Slide 27 of 56 Slide 30 of 56 Prognosis in Compensated Cirrhosis Median survival 9-12 years Deaths: Non-liver related (Cardiovascular, stroke, etc.) Liver-related deaths: HCC Predictors of decompensation: MELD score HR 1.15 Serum albumin HR 0.37 Chronic liver disease Management of Compensated Cirrhosis Compensated cirrhosis Diagnosis: Liver biopsy Clinical/Imaging Screen for varices (EGD): Large varices beta-block/evl Small varices EGD in 1-2 yrs No varices EGD in 2-3 yrs Screen for HCC: Ultrasound every 6 months Decompensated cirrhosis Liver transplant (LT) Slide 31 of 56 Death Stop alcohol Vaccinations Lifestyle changes Chicago, IL: May 19, 2015 (INTRODUCTORY) 9

10 From: Coffee, Cirrhosis, and Transaminase Enzymes Arch Intern Med. 2006;166(11): doi: /archinte Slide 32 of 56 N=125,580 F/U 22 yrs Date of download: 4/18/2014 Copyright 2014 American Medical Association. All rights reserved. From: Coffee, Cirrhosis, and Transaminase Enzymes Arch Intern Med. 2006;166(11): Slide 33 of 56 N=125,580 F/U 22 yrs Copyright 2014 American Medical Association. All rights reserved. Chicago, IL: May 19, 2015 (INTRODUCTORY) 10

11 Wake up and drink the coffee Slide 35 of 56 Cirrhosis: Median Survival Based on Complications Compensated cirrhosis Decompensated cirrhosis Jaundice Encephalopathy Ascites Variceal hemorrhage Hepatopulmonary syndrome Spontaneous bacterial peritonitis 9-12yrs 2 years 10 months 9 months Hepatorenal syndrome Type 2 (Refractory ascites) 6 months Type 1 (Creatinine > 2.5mg/dL) <6 weeks Slide 36 of 56 Chicago, IL: May 19, 2015 (INTRODUCTORY) 11

12 Slide 37 of 56 Slide 38 of 56 Infections in Patients with Cirrhosis Retrospective review of 178 studies Mortality at 1, 3, and 12 months determined Comparison with non-infected cohort Infection-Related Risk of Death Slide 39 of 56 Chicago, IL: May 19, 2015 (INTRODUCTORY) 12

13 Evolving Concepts in Allocation: Mortality Rates by MELD Transplant Benefit Waitlist Transplant Slide 40 of 56 Mortality rate per 1000 patients HR=3.64 P<0.001 HR=2.35 P<0.001 HR=1.21 P=0.41 HR=0.62 P<0.01 HR=0.38 P<0.001 HR=0.22 P<0.001 HR=0.18 P<0.001 HR=0.07 P<0.001 HR=0.04 P< MELD HR=hazard ratio Slide 43 of 56 Immunizations Pneumococcal, influenza, and tetanus vaccines mandatory Hepatitis A and B vaccines after serologic testing for previous exposure Risk of inadequate antibody response associated with hepatic disease severity Live attenuated vaccines not contraindicated (CDC) Nyberg LM, EASL, 2014, O67 Slide 44 of 56 Comorbid Conditions Associated with Decision Making Regarding HCV Treatment in a Large US HMO Retrospective study using Kaiser Permanente database to compare characteristics of those treated vs. those not treated for HCV using IFN-based therapy and to identify significant predictors of not receiving treatment Factors associated with receiving treatment included age 45 65, male gender, cirrhosis, HIV, NAFLD, depression, prior liver transplant 15% (7,945/51,984) of the total number of patients identified with HCV were treated 17% (5,533/32,283) of the study population were treated 42% of the total study population were likely IFN-ineligible or intolerant 50% of the study population had a significant comorbid illness 15% were treated, 85% were not treated Factors Associated with NOT Receiving Treatment Independent variables Odds Ratio P-value Anemia < Autoimmune disorder Renal dysfunction Cardiovascular disease < Psychosis/Bipolar Severe lung disease < Substance abuse < MELD ( 12) < Chicago, IL: May 19, 2015 (INTRODUCTORY) 13

14 Slide 47 of 56 Normal ALT Abn. ALT Liver disease, no statin N=2245 Statin duration (yr) Statin discontinue 10.7% 11.1% AST/ALT 1-10 xuln AST/ALT >10 xuln Risk of Statin Hepatotoxicity 1.7% 4.7% 6.4% p=0.002 p= % 0.6% 0.4% p=0.6 p=0.6 (Chalasani Gastroenterology 2004) Pravastatin in patients with chronic liver disease Slide 48 of 56 Inclusion LDL > 100 mg/dl Chronic liver disease: 64% NAFLD 24% HCV 12% other % T cholesterol Pravastatin (n=160) Placebo (n=160) 20%* 3% % LDL 31% * 3% % ALT > 2X BL 7.5% 12.5% Time to ALT and cumulative % at week 36 similar (Hepatology 2007 Nov; 46:1453) Slide 49 of 56 1 Asymptomatic elevations in aminotransferases are a class effect of statins and do not indicate liver dysfunction 2 Liver failure causing death or hospitalization or requiring liver transplantation is very rare with statins 3 Current evidence does not support routine monitoring of liver enzymes and liver biochemistries in patients receiving statins 4 Presence of chronic liver disease and Child s A cirrhosis should not be considered a contraindication for statin use 5 Current evidence supports use of statins to treat hyperlipidemia in patients with nonalcoholic fatty liver disease and NASH AJC Volume 97, Issue 8, Supplement 1 Chicago, IL: May 19, 2015 (INTRODUCTORY) 14

15 Pharmacotherapy Slide 50 of 56 Acetaminophen usually OK (< 2 grams daily) Avoid use of NSAIDs, aspirin with decompensation, ascites Antibiotics Fluoroquinolones, cephalosporin OK Oral hypoglycemic agents if cirrhosis is compensated; insulin if decompensated Nutrition Protein-calorie malnutrition Frequent, high-calorie small meals Bedtime snacks Check fat-soluble vitamins / zinc, and replace accordingly Slide 51 of 56 Fatigue Slide 52 of 56 Major factor in reduced quality of life Can be a manifestation of encephalopathy Co-morbidities (obesity, depression, sleep apnea) Exclude medical causes (anemia, thyroid disease) No effective medical therapy identified Chicago, IL: May 19, 2015 (INTRODUCTORY) 15

16 Depression Prevalence rate of 30%-40 % Pharmacologic therapy is safe SSRI Mirtazapine Slide 53 of 56 Muscle Cramps Slide 54 of 56 Major factor in poor quality of life Independent of age, disease severity, diuretic use No evidence-based therapy available Antioxidants ineffective Cirrhosis: Sexual Dysfunction Mechanisms Unclear Slide 55 of 56 Sildanefil is safe in compensated cirrhosis. World J Gastroenterol 2008; 14(40): Chicago, IL: May 19, 2015 (INTRODUCTORY) 16