Approach to Acute Hepatitis other than. Dan Kottachchi, MD, MSc, FRCP

Transcription

1 Approach to Acute Hepatitis other than viral Dan Kottachchi, MD, MSc, FRCP

2 General approach Step 1 Yes Acute Liver Failure (ALF) INR 1.5 any degree of encephalopathyy) in a patient without preexisting cirrhosis No Sigh of relief Continue to step 2 Contact regional transplant center/hepatologist INR, electrolytes, bicarbonate, Ca, Mg, P04, glucose, AST, ALT, ALP, GGT, tbili, unconj bili, Alb, Cr, BUN, ABG, lactate, beta-hcg (women), Amylase, lipase CBC, group and screen, Tylenol level, Toxicology screen Anti-HAV IgM, HBsAg, anti-hbc, anti-hev (if suspected or pregnant), anti- HCV, HCV RNA, HSV1 IgM, VZV, EBV, CMV Ceruloplasmin Arterial ammonia? Autoimmune hepatitis markers (ANA, SMA, immunoglobulins, anti-lkm, anti-lc1) HIV U/S Doppler flow or CT or MRI

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4 Step 2 AST and ALT ratio >4:1 No Yes Get a CK! Hemolysis w/u (also think Wilson s) Yes AST and ALT in the 1000s No Acute viral (remember E, rarely C) Drugs & Herbs: Tylenol overdose, Amanita phalloides Autoimmune hepatitis Ischemic Acute Wilson s HELLP Stone passage Continue to Step 3

5 Drugs Acetaminophen (APAP) Typical ALF exceeds 10 gm/day (>150 mg/ kg) low or absent levels do not rule out hepatotoxicity FDA recommends no more than 325 mg of APAP per dose cease prescribing combination drug products with more than 325 mg of APAP per tablet

6 APAP cont. Liver enzyme elevations usually follow symptoms Symptoms are within 24hrs Enzymes usually start going up 24-72hs with marked elevations hrs (stage 3) King s college criteria still has prognostic value, phosphate may also Activated charcoal 1gm/kg within 3-4 hrs of ingestion Doesn t interfere with oral NAC Rumack-Matthew nomogram within 24 hrs of ingestion Has not been validated for chronic ingestions Liberal indications for NAC ALF in APAP is a transplantable condition Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update. J Clin Transl Hepatol Jun 28;4(2): doi: /JCTH Epub 2016 Jun 15. Review.

7 Amanita phalloides Death cap Amatoxin is a hepato and nephrotoxic 1 st phase Asymptomatic 2 nd phase Diarrhea, nausea and vomitting (avg 10 hrs post-ingestion) Diarrhea onset <8hrs after ingestion poor prognosis 3 rd phase Recovery or clinical improvement 3 rd phase Bloodwork only abnormality!!! ALF fourth phase Tx: Peng G, NAC, Silibinin, MARS à transplant Smith MR1, Davis Mycetismus: a review May;4(2): doi: /gastro/gov062. RL2.Gastroenterol Rep (Oxf). Epub 2015 Dec 4.

8 Ischemic Hepatic resting blood flow is ~25% of CO (1-2 L per min) 75% is portal vein 25% is hepatic (proper) artery Significant compromise can occur at any stream of the circulatory network Portal vein thrombosis Budd-Chiari Shock

9 Ischemic - PVT Thrombosis that develops in the trunk of the portal vein including its right and left intrahepatic branches Acute vs chronic (Extra Hepatic Portal Venous Obstruction) Cirrhotic vs non-cirrhotic

10 Ischemic - PVT Non-cirrhotic Acute abdominal pain (91%), fever (53%), ascites (38%) (small volume ascites detectable only on imaging in 33% and clinical ascites in 5%) Bowel infarction too Chronic Upper GI bleeding often first presentation Cirrhotic Incidence high (11% or higher in Child B/C) Asymptomatic 40-50%

11 Ischemic PVT Treatment Non-cirrhotic Acute Anticoagulate 6mo vs lifelong ~40% will recanalise Thombolysis or thrombectomy (rarely done) Chronic Treat complications first Cirrhotic Partial vs complete thrombosis anticoagulated if risk of progressing or transplant eligible Yogesh K. Chawla and Vijay Bodh Portal Vein Thrombosis J Clin Exp Hepatol Mar; 5(1): Published online 2015 Jan 6. doi: /j.jceh PMCID: PMC

12 Ischemic Budd-Chiari Primary flow is obstructed due to an endoluminal aberration Thrombosis most common Secondary Compression or invasion outside of the hepatic venous outflow tract Get flow assessment LMWH to vitk antagonist High number of HIT vs other uses so avoid UFH decompressive therapies Thrombolytic therapy and angioplasty Surgical portosystemic shunt TIPS or OLT Martens P, Nevens F. Budd-Chiari syndrome. United European Gastroenterol J Dec;3(6): doi: /

13 Autoimmune hepatitis (AIH) Can present acutely or in a more chronic pattern Asymptomatic to fulminant Characterize by hypergammaglobulinemia Type 1 90% ANA, SMA, HLA DR3/4/13 Type 2 10% Anti-LKM1, anti-lc1 Can have overlap syndromes (variants) J Hepatol Oct;63(4): doi: /j.jhep Epub 2015 Sep 1. EASL Clinical Practice Guidelines: Autoimmune hepatitis. European Association for the Study of the Liver.

14 Autoimmune hepatitis (AIH) - Treatment

15 Wilson s disease (WD) WD is a monogenic, autosomal recessively inherited condition Mutation in ATP7B Hepatic involvement can be as early as age of 9 months Neurologic issues in 2 nd /3 rd decade Bandmann O, Weiss KH, Kaler SG /S (14) Wilson's disease and other neurological copper disorders. Lancet Neurol Jan;14(1): doi: Robers, E, Schilsky M. Diagnosis and Treatment of Wilson s Disease. Hepatology 2008.

16 Wilson s Disease Fulminant presentation may occur Age alone should not be the basis for eliminating Wilson s Look for hemolytic anemia Look for low ALP and uric acid levels

17 Wilson s disease (WD)

18 Wilson s disease therapy

19 HELLP Big hint they are pregnant! Severe form of pre-eclampsia de novo hypertension after the 20th week of pregnancy (blood pressure (BP) 140/90) combined with proteinuria (>300 mg/day), other maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction right upper quadrant or epigastric pain -65% of cases nausea and vomiting ~35% of cases headache ~30% of cases Imaging imperative in HELLP Rule out hepatic infarction, rupture or hemorrhage BP control, +/-glucorticoids, Mg Delivery of the placenta

20 Going back.. Step 2 AST and ALT ratio >4:1 No AST and ALT in the 1000s No Continue to Step 3

21 Step 3

22 EXCEPT.. Alcoholic hepatitis Classic AST:ALT ratio of 2:1? Related to pyridoxine deficiency AST rarely exceeds 300 IU/dl (in acute) Suspect other (additional) etiology if higher Abstinence for several weeks required to normalize AST Isolated hyperbilirubinemia can occur

23 Prognosis - Mayo Endstage Liver Disease (MELD) MELD >20 (optimal) and > 18 and DF >32 In-hospital mortality ú MELD >18 sensitivity 85%, specificity 84% ú MELD >20 sensitivity 91%, specificity 85% ú DF sensitivity sensitivity 83%, specificity 60%

24 Steroids

25 Lille model * (age in years) * (albumin day 0 in g/l) * (evolution in bilirubin level in µm) * (renal insufficiency) *(bilirubin day 0 in µm) * (prothrombin time in seconds) ú Renal insufficiency 0 if absent or 1 if Cr > 115 µm/l ú Evolution of bilirubin was absolute change from day 0 to 7 ú Predicting survival after 7-days of steroids ú Lille score <0.45 continue steroids! ú

26 Pentoxifylline Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a randomised controlled trial.forrest E, Mellor J, Stanton L, Bowers M, Ryder P, Austin A, Day C, Gleeson D, O'Grady J, Masson S, McCune A, Patch D, Richardson P, Roderick P, Ryder S, Wright M, Thursz M Trials Aug 19; 14():262

27 NAC significant decrease in mortality with combination therapy at 1 month (8% vs. 24%, p= 0.006) but not at 6 months (27% vs. 38%, p = 0.07) death due to hepatorenal syndrome was less frequent in the combination group than in the steroid monotherapy group at 6 months (9% vs. 22%, p = 0.02). N-acetylcysteine on day 1 (dose of 150, 50, and 100 mg per kilogram of body weight in 250, 500, and 1000 ml of 5% glucose solution over a period of 30 minutes, 4 hours, and 16 hours, respectively) days 2 through 5 (100 mg per kilogram per day in 1000 ml of 5% glucose solution). Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365: doi: /NEJMoa

28 Questions Feel free to