1. Alcoholic hepatitis Hospitalist Best Practice J Rush Pierce Jr, MD, MPH Lenny Noronha, MD September 11, 2013

2. Disclosures Financial: none Affiliations/biases – I drink alcohol – I have a close relative with alcoholism – Evidence should inform our thinking Hospitalist Best Practice: Alcoholic hepatitis09/11/20132

3. Roadmap for today Describe case Review recommended evaluation & treatment Review the role of MELD and Maddrey’s discriminant calculations Review the literature regarding treatment Discuss discharge criteria Review the role of palliative care Hospitalist Best Practice: Alcoholic hepatitis09/11/20133

4. Learning Objectives 1.List diagnostic criteria for alcoholic hepatitis. 2.Describe how to use an on-line calculator to predict prognosis and treatment for patients with alcoholic hepatitis. 3.List recommended treatments for alcoholic hepatitis. Hospitalist Best Practice: Alcoholic hepatitis09/11/20134

5. Case A 53 year-old man with a long history of daily alcohol use presents with one week of jaundice. BP = 95/60 mm Hg, P = 105/minute, and T = 38.0  C. Exam discloses icterus, ascites, and an enlarged, tender liver. Bilirubin = 9 mg/dl, AST = 250 IU/dl, ALT = 115 IU/dl, prothromin time = 22 secs, INR 2.7, creatinine = 0.9 mg/dL, WBC = 15,000/cu mm with 70% neutrophils. How should he be treated? Hospitalist Best Practice: Alcoholic hepatitis09/11/20135

6. Questions you might have What is his diagnosis? What evaluation should he have? What is his prognosis? How should he be treated? Do we need to call GI? How do we monitor his progress? When can he leave the hospital? 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis6

7. What is his diagnosis? Regular, heavy alcohol consumption can be associated with a variety of forms of liver disease, including fatty liver, inflammation, hepatic fibrosis and cirrhosis. The term alcoholic hepatitis describes a more severe form of alcohol-related liver disease associated with significant short-term mortality. 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis7

8. Typical clinical and laboratory features of alcoholic hepatitis FeatureCriteria for alcoholic hepatitis History10 or more years of daily drinking, recent jaundice Examjaundice, enlarged liver Bilirubin> 5 mg/dL AST and ALTboth elevated but both < 400 IU/dL AST/ALT ratio> 2 INRelevated Absolute neutrophil count> 7,700 cells/cu mm 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis8

9. What evaluation should he have? Confirm the diagnosis Predict prognosis with MELD and Maddrey’s Infectious work-up – ordering blood and urine cultures – chest x-ray – paracentesis to exclude SBP 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis9

10. Common scoring systems used in management of alcoholic hepatitis Scoring systemData needed to calculate UseInternet calculators MELD – Alcoholic hepatitis Bilirubin, creatinine, INR 90-day prognosishttp://www.mayocl inic.org/meld/may omodel7.html Maddrey’s discriminant function (mDF) Protime, protime control (13 at UNMH), bilirubin Consideration of anti-inflammatory treatment http://www.mdcalc.com/maddreys- discriminant- function-for- alcoholic-hepatitis/ Lille ModelDOB, albumin, creatinine, protime at day 0; Bilirubin at days 0 and 7 To judge response to therapy, predict 6-month prognosis after treatment http://www.lillemo del.com/score.asp 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis10

11. How should he be treated? TreatmentTherapeutic optionsComments Abstinence from alcoholrehab programs, self-help groups, acamposate, baclofen, disulfiram, naltrexone Usually after discharge NutritionEating, tube feedingsGoal = 35 – 40 kcal/kg per day CorticosteroidsPrednisolone40 mg daily for 28 days followed by a 2 week taper Phosphodiesterase inhibitors Pentoxifylline400 mg TID for 28 days 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis11

12. Nutrition Enteral nutritional support was shown in a multicenter observational study to be associated with reduced infectious complications and improved one year mortality ACG recommends 35 – 40 kcal/kg per day and protein intake 1.2 – 1.5g/kg per day. In the average 70 kg patient this is 2,450 – 2,800 kcal/day 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis12

13. Corticosteroids Recommended by ACG for Maddrey’s > 32 Cochrane 2008 review – 15 trials with 721 randomized patients – No overall mortality reduction – Mortality reduced w/Maddrey’s > 32 & HE Another meta-analysis demonstrated a mortality benefit when the largest studies with 221 patients Maddrey’s >32 were analyzed separately 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis13

14. Corticosteroids Prednisolone is preferred over prednisone because it is the active drug. Concerns include hyperglycemia and increased risk of infection. Contraindications – active infection – gastrointestinal bleeding – acute pancreatitis – renal failure. 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis14

15. Pentoxifylline Recommended by ACG if corticosteroids are contraindicated A 2008 double-blind, placebo controlled trial (n=101) demonstrated decreased 28-day mortality (24.6% vs. 46% receiving placebo) Cochrane review of all studies concluded that no firm conclusions could be drawn Small randomized trial (n= 68) showed pentoxifylline superior to prednisolone 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis15

16. Pentoxifylline Can be prescribed to patients who have contraindications to corticosteroid use Dose =400 mg TID for four weeks. Common side effects are nausea & vomiting Cannot be administered by NG tube Should not be used in patients with recent cerebral or retinal hemorrhage. 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis16

17. DC Med Costs UNM CostUNM Care Co-paySelf Pay Prednisolone 40mg daily #21 (3wks) $1.50$7$10 Pentoxifylline 400mg tid #84 (4 wks) $8$7$100 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis17

18. Prognosis Case patient MELD = 26 – Confers 43% - 3 month mortality Higher if HE or ascites present – High probability to have cirrhosis if he does survive episode of AAH How should you tell this to patient/family? What considerations follow in this regard? 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis18

19. Lille Model 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis19 Louvet. Hepatology 2007;45:1348

20. 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis20 Alcoholic liver disease: proposed recommendations for the American College of Gastroenterology Arthur J McCullough and J F Barry O' Connor, Am J Gastr, 1998, 93, 2022-2036.

21. Brief Report on UNMH ‘10-’12 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis21 Total 467 pts 107 Readmissions

22. UNMH AAH ‘10-’12 cont’d 33 initially adm to MICU 143 spent time in MICU during admission Median age 45 49 died in hospital – Another 33 reported deaths within 90 days of dc 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis22

23. UNMH AAH ‘10-’12 Dispo* 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis23 *based on dc order

24. Great reasons to consult Palliative High mortality condition in young people – Assess understanding of diagnosis/prognosis – Family support – Reinforce your team’s communication (i.e. NG feeds, transplant candidacy, DC) – Support your team – Continuity for pt during long hospitalization Ward team handoff/ICU transfer 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis24

25. Early Consultation Preferred! All patients c AAH, DF > 32 Please consult as soon as diagnosis suspected – Time to establish rapport 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis25

26. Palliative Care Consultation Goals of Care Advance Care Planning – Describe dispo options (i.e. SNF, NH, home) – ICU transfer, rehospitalization? – Surrogate decision maker Documentation Guidance to clarify wishes – Code status Patient advocacy Assess spiritual care needs 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis26

27. Discharge considerations No clinical trials have studied optimal timing of discharge. Expert opinion based on clinical experience recommends that patients be kept in the hospital until they are eating, signs of alcohol withdrawal and encephalopathy are absent, and bilirubin is less than 10 mg/dl Attention to abstinence from EtOH is paramount 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis27

28. Alcoholic hepatitis - approach 1.Determine that pt fits the clinical picture 2.Admit and cessation of alcohol 3.Order folate, thiamine, MVI, and vitamin K. 4.Add a note about potential withdrawal to hand-off report. 5.Order an infectious work-up (blood and urine cultures, CXR, and paracentesis). 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis28

29. Alcoholic hepatitis - approach 6.Dietary consult for calorie counts, importance of > 2,500 cals/day. 7.Consider tube feedings if not meeting goal 8.Determine Maddrey’s and MELD scores 9. Order prednisolone 40 mg daily; if actively bleeding or infected, Trental 400 mg TID 10. Determine Lille score treatment day 7 11. Discuss code status and end-of life issues 12. Consider GI consult 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis29

30. Alcoholic hepatitis – areas of possible consensus Use of NG feedings for nutrition When to call GI When to call palliative care Evaluation of afebrile leukocytosis Discharge criteria 09/11/2013Hospitalist Best Practice: Alcoholic hepatitis30