The Liver for the Nonhepatologist

Transcription

1 The Liver for the Nonhepatologist Michael R. Charlton, MBBS, FRCP Professor of Medicine University of Chicago Chicago, Illinois Overview Initial assessment of liver disease 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 Extrahepatic manifestations of HCV Mixed cryoglobulinemia (type II and III) Prevalence of HCV 80-90%; reverse 30-50% Glomerulonephritis- MPGN Porphyria cutanea tarda Lymphoma (B cell) HCV present in 9-32% Type II DM OR 3.77 ( ) Lichen Planus Vitiligo CNS

2 Natural History of Chronic Liver Disease 20+ years 5-10 years 1-5 years Chronic liver disease Compensated cirrhosis Decompensated cirrhosis Death Development of complications: Variceal hemorrhage Ascites Encephalopathy Jaundice HCC Natural History of Chronic Liver Disease New Paradigm Treated Untreated HCV Accelerates Non-Liver Mortality in HIV- Infected Patients: A Nationwide Cohort Study Of 69,913 HIV-infected patients 2,366 deaths occurred in 247,484 patient-years Overall mortality higher in 8,283 (7.5%) HIV/HCV co-infected patients vs. 59,476 (2.8%) in HIV patients (HR 1.79, P<0.0001), while it did not differ in 2,154 (3.9%) HIV/HBV patients (HR 1.21, P=0.09) Non-liver-related mortality as well as non-liver, non-aids-related mortality remained higher in HIV/HCV co-infected patients (HR 1.36, P< and HR 1.43, P<0.0001, respectively) Survival Probability Overall Mortality With Number of Subjects at Risk Logrank p<.0001 HIV HIV/HBV HIV/HCV Month from January 2008 HCV-/HBV- HCV-/HBV+ HCV+/HBV- HCV infection increases overall and non-liverrelated mortality in HIV-infected patients HCV treatment should be recommended for HCV co-infection as it is for HBV co-infection

3 Does my patient have cirrhosis? Is a liver biopsy essential for diagnosis of cirrhosis? 1. Yes 2. No Is a liver biopsy essential for diagnosis of cirrhosis? 1. Yes 2. No

4 Normal Cirrhosis Irregular surface Nodules Cirrhosis - Diagnosis Cirrhosis is a histological diagnosis However, in patients with chronic liver disease, various clinical, laboratory, and radiological features can suggest cirrhosis Clinical Stigmata

5 Diagnostic Algorithm Chronic liver disease and any of the following: Variceal hemorrhage Ascites Hepatic encephalopathy Yes Physical findings: Laboratory findings: No Enlarged left hepatic lobe Thrombocytopenia Splenomegaly Impaired hepatic synthetic function Stigmata of chronic liver disease Yes Radiological findings: No Small nodular liver Intra-abdominal collaterals Ascites Splenomegaly MRE > 5 kpa Yes Liver biopsy not necessary for the diagnosis of cirrhosis No Consider Liver biopsy Non-invasive measurement of hepatic fibrosis SERUM MARKERS TRANSIENT ELASTOMETRY FibroTest ELF Panel Fibromètre NAFLD fibrosis score Fibrometer biopredictive.com Biols.fr 33 MR Elastography of the Liver +70 Phase Difference θ Gradient-Echo MRE 0 Amplitude (mm) Active Driver Plastic Tube Passive Driver 0-90 Amplitude (mm)

6 Liver Stiffness Correlates With Fibrosis Stage Liver Stiffness (kpa) Normal Yin et al. CGH 2007;5: < * < * < * Kruskal Wallis Dunnett s Test α = Chronic Liver Disease (Fibrosis Stage) exams exams exams exams exams exams MRE Liver Stiffness Predicts Outcomes Asrani et al., Journal of Hepatology EPUB ahead of print

7 Clinical Interpretation of MRE Results 2.9 kpa 3.0 to 4.9 kpa 5 kpa No imaging features of cirrhosis Imaging features of cirrhosis Biopsy not required Biopsy required for staging Biopsy required for staging Biopsy not required What is the Natural History of Cirrhosis? Prognosis in Cirrhosis Compensated or Decompensated?

8 The most common cause of death in patients with compensated cirrhosis is: 1.Variceal bleeding 2.HCC 3.Hepatic encephalopathy 4.Cardiovascular The most common cause of death in patients with compensated cirrhosis is: 1.Variceal bleeding 2.HCC 3.Hepatic encephalopathy 4.Cardiovascular Prognosis in Compensated Cirrhosis Median survival 9-12 years Deaths: Non-liver related (Cardiovascular, stroke etc.) Liver-related deaths : Predictors of decompensation: HCC MELD score HR 1.15 Serum albumin HR 0.37

9 Management of Compensated Cirrhosis Chronic liver disease Compensated cirrhosis Diagnosis: Liver biopsy Clinical/Imaging Decompensated cirrhosis Death Screen for varices (EGD): Large varices beta-block/evl Small varices EGD in 1-2 yrs No varices EGD in 2-3 yrs Liver transplant (LT) Screen for HCC: Ultrasound every 6 months Stop alcohol Vaccinations Life-style changes From: Coffee, Cirrhosis, and Transaminase Enzymes Arch Intern Med. 2006;166(11): doi: /archinte 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): N=125,580 F/U 22 yrs Copyright 2014 American Medical Association. All rights reserved.

10 Associations between the Consumption of 4 or More Cups of Coffee per Day and Mortality Overall Hazards ratio = 0.88 (95% CI, 0.84 to 0.93) P<0.001 N=617,000 follow up 5,148,000 person years Freedman ND et al. N Engl J Med 2012;366: Wake up and drink the coffee Cirrhosis: Median Survival based on Complications Compensated Cirrhosis 9-12yrs Decompensated Cirrhosis Jaundice Encephalopathy Ascites Variceal hemorrhage Hepatopulmonary syndrome 2 years 10months Spontaneous bacterial peritonitis 9 months Hepatorenal syndrome Type 2 (Refractory ascites) 6 months Type 1 (Creatinine > 2.5mg/dL) <6 weeks

11 Retrospective review of 178 studies Mortality at 1, 3, 12 months determined Comparison with non-infected cohort Infection related Risk of Death Evolving Concepts in Allocation: Mortality Rates by MELD Transplant Benefit Waitlist Transplant 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

12 Which of the following vaccines is CONTRAINDICATED in cirrhosis 1. MMR 2. Typhoid 3. OPV 4. BCG 5. None of the above Which of the following vaccines is CONTRAINDICATED in cirrhosis 1. MMR 2. Typhoid 3. OPV 4. BCG 5. None of the above Immunizations Pneumococcal, influenza, and tetanus vaccines mandatory Hepatitis A and B vaccine after serologic testing for previous exposure Risk of inadequate antibody response associated with hepatic disease severity Live attenuated vaccines not contraindicated (CDC)

13 Pharmacotherapy in Cirrhosis A 55-year-old woman with a BMI of 35 kg/m 2 has a total serum cholesterol is 382 mg/dl, with LDL cholesterol 198 mg/dl after attempted dieting for 3 months. The AST is 98 U/L (<43), and the ALT 114 U/L (<45). Ultrasound examination demonstrates features consistent with cirrhosis. Clinically, well compensated. She asks about statins What would be your recommendations? 1.Avoid statins 2.Start statins and monitor AST and ALT every week for 6 weeks. 3.Initiate statins and monitor AST and ALT at 2 weeks, 6 weeks, 3 months, and 6 months 4.Initiate statins and watch for myalgias and muscle weakness 5.Statins if liver biopsy does not show cirrhosis Pharmacotherapy in Cirrhosis A 55-year-old woman with a BMI of 35 kg/m 2 has a total serum cholesterol is 382 mg/dl, with LDL cholesterol 198 mg/dl after attempted dieting for 3 months. The AST is 98 U/L (<43), and the ALT 114 U/L (<45). Ultrasound examination demonstrates features consistent with cirrhosis. Clinically, well compensated. She asks about statins What would be your recommendations? 1.Avoid statins 2.Start statins and monitor AST and ALT every week for 6 weeks. 3.Initiate statins and monitor AST and ALT at 2 weeks, 6 weeks, 3 months, and 6 months 4.Initiate statins and watch for myalgias and muscle weakness 5.Statins if liver biopsy does not show cirrhosis Normal ALT Abn. ALT Liver disease, no statin N=2245 Statin duration (yr) 0.48± ±0.08 Statin discontinue 10.7% 11.1% AST/ALT 1.7% 4.7% 6.4% 1-10 xuln p=0.002 p=0.2 AST/ALT >10 xuln Risk of Statin Hepatotoxicity 0.2% 0.6% 0.4% p=0.6 p=0.6 (Chalasani Gastroenterology 2004)

14 Pravastatin in patients with chronic liver disease 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) 1 Asymptomatic elevations in aminotransferases are a class effect of statin 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 Pharmacotherapy Acetaminophen usually OK (< 2 grams daily) Avoid use of NSAID s, aspirin with decompensation, ascites Antibiotics Fluoroquinolones, cephalosporin OK Oral hypoglycemic agents if cirrhosis is compensated; insulin if decompensated

15 Nutrition Nutrition Protein-calorie malnutrition Frequent, high-calories small meals Bed time snacks Check fat-soluble vitamins / zinc, and replace accordingly Fatigue 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

16 Depression Prevalence rate of 30%- 40 % Pharmacologic therapy is safe SSRI Mirtazapine Muscle Cramps Major factor in poor quality of life Independent of age, disease severity, diuretic use No evidence-based therapy available Antioxidants ineffective Cirrhosis: Sexual Dysfunction Erectile dysfunction is common (~40%) in patients with cirrhosis. Sildanefil, which is almost completely hepatically metabolised (cyt P450 3A4), is safe in compensated cirrhosis. World J Gastroenterol 2008; 14(40):

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