Elevated Liver Tests Lisa M. Glass, MD October 19, 2017

Clinical Case 1:

HPI: 67 year old woman with a h/o chronic UTIs presents with a several month history of fatigue and epigastric pain that progressed to include intermittent fevers (Tmax of 101ºF)

PMH: Sjogren’s syndrome, SLE, Breast cancer: partial mastectomy with XRT, Obesity

Meds: Omeprazole 40mg daily, Macrodantin 50mg po QHS

Social Hx: Married with two adult children EtOH use: minimal throughout life IV or intranasal DU: never Tattoos, blood transfusions: none

Clinical Case 1:

•  Physical Exam: –  VS: T: 98.7 HR: 85 BP: 137/78 –  Gen: Alert, oriented, NAD –  HEENT: Icteric sclera –  Abd: Nondistended, bowel sounds present, tender to palpation in RUQ, no

rebound/guarding –  Skin: Notable jaundice; no palmar erythema, spider angiomas

•  Labs: –  Cr 0.8 –  Alb: 3.3/AST 584/ ALT 345/ AP 159/ TB 13 –  WBC 6.5/HGB 12.8/ Plt 234 –  INR 1.1

1.  Schedule PCP follow-up in 2 weeks 2.  Refer to liver clinic next available (4-6 weeks) 3.  Refer to liver clinic urgent (within 10 days) 4.  Direct hospital admission 5.  Send to emergency department

Next step in management: what would you do now?

•  Acute Liver failure: –  Mental status changes –  Hepatitis/Jaundice –  Coagulopathy

•  Other worrisome features: –  Fever –  Acute abdominal pain –  Rapid ascites accumulation

Patient Triage: Red-flag signs in acute liver disease

•  History: –  Medications/herbs, drug or alcohol use –  Exposures to others with hepatitis –  Parenteral risks: blood transfusion, needle sticks, or tattoos –  Travel, diet, raw seafood, shellfish –  Previous hepatitis or jaundice –  Autoimmune diseases

•  Keys to Physical Assessment: –  Careful Neurologic assessment

•  Asterixis or altered mental status •  Tremor: withdrawal •  Movement disorder or pyschiatric disturbance

–  Look for stigmata of chronic liver disease •  Telangectasia, palmar erythema, palpable spleen, umbilical hernia , caput

medusae, ascites

Initial Approach:

AcuteHepa**s

Acuteviralhepa**s

Alcoholichepa**sChronicHepa**sCChronicHepa**sBNASH/NAFLDHemochromatosisCholesta*cAutoimmunedisease

ChronicHepa**s

Autoimmunehepa**s

Druginducedtoxicity

Ischemic/hypoxicInjury(shockliver,BuddChiari)

BiliaryObstruc*on:Gallstones,stricture,cholangi*s,extrinsiccompression

Wilson’sDisease

<100>1000sTransaminases

•  History: –  Significant EtOH intake

(>100g/day) –  Symptoms can start days to

weeks after EtOH cessation

•  Presentation: –  Rapid onset of jaundice,

abdominal distension, ascites –  +/- Fever –  Encephalopathy –  Enlarged and tender liver

•  Laboratory studies: –  AST > 2x ULN

•  rarely above 300 IU/ml –  AST/ALT ratio >2 –  Leukocytosis –  Increased bilirubin, INR,

creatinine –  Hemolysis

•  Treatment: –  Steroids for Maddrey’s DF >32

•  Absence of infection, renal failure and GI Bleeding

–  Abstinence is the only predictor of improved long-term mortality

Differential Diagnosis: Acute alcoholic hepatitis

•  Background: –  Responsible for 10% of all cases

of acute hepatitis –  Most common cause of liver

failure in the U.S. –  Culprit Medications:

1.  Acetaminophen 2.  Antibiotics: Augmentin

•  History: –  Timing: 5 days – 3 months

typical –  Exclude other possible

causes

Differential Diagnosis: Drug induced liver injury

•  Presentation: –  Varied: asymptomatic liver

test elevation to fulminant failure

–  +/- Fever –  Fatigue –  Rash –  Nausea and vomiting

Hepatocellular Mixed

ALT <2x ULN Alk phos >ULN

ALT >2xULN Alk phos >ULN

Acetaminophen Amiodarone

Isoniazid Ketoconazole Methotrexate Monocycline

Sertraline Statins

Tetracycline Valproic acid

Amoxicillin-Clavulanate Azathioprine Clindamycin

Carbamazepime Cyclosporine Methimazole Nitrofurantoin

Phenytoin Trimethoprin-

Sulfamethoxazole

Anabolic steroids Estrogen

Erythromycin OCP’s

Terbinafine Tryciclics

ALT >2xULN Alk phos WNL

Cholestatic

DILI: Drugs and pattern of injury

Is there a role for Acetaminophen in known chronic liver disease?

1.  Yes, absolutely it is a safe drug because the toxic range is understood

2.  No, one must avoid this drug in patients with any known liver disease

3.  Not sure

Is there a role for statins in known chronic liver disease?

1.  Yes, absolutely it is a safe drug, even in patients with chronic liver disease

2.  No, one must avoid this drug in patients with any known liver disease

3.  Not sure

•  History: –  Identify risk for recent exposure: Drug

use, blood transfusion, new sexual partner, needlestick, travel/restaurants

•  Presentation: –  Frequently asymptomatic –  Fatigue –  Nausea and vomiting –  Jaundice –  RUQ pain

•  Laboratory studies: –  Depends on timing of presentation –  Serologic evaluation to diagnose

•  Treatment: –  Supportive care –  HAV post-exposure prophylaxis

(within 14 days of exposure) •  Healthy persons aged 1-40 years: HAV

vaccine •  Persons +41 years, <12 months,

Immunocompromised: Immune globulin

–  Monitor for progressive or acute liver failure, typically only in acute HBV

–  Antiviral medications in some cases of acute HBV

Differential Diagnosis: Acute Viral Hepatitis

1.  Anti-HAV IgG; Anti-HBc IgM; Anti-HCV

2.  Anti-HAV IgM; Anti-HBc IgG; HCV RNA PCR

3.  Anti-HAV total; HBs Ag; Anti-HCV

4.  Anti-HAV IgM; Anti-HBc IgM; HCV RNA PCR

Testing for Acute Hepatitis:

•  Initial Presentation: –  Wide range of signs and symptoms:

•  Asymptomatic to arthralgia and fatigue to acute liver failure –  Incidence:

•  1-2/100,000 persons in US –  Female to male ratio: 3.6:1 –  Peak ages 16-30 years:

•  50% >30 years, 23% ≥ 60 years •  Diagnosis:

–  Elevation of ALT or AST –  Elevation of IgG (>1.5x the ULN more suggestive) –  ANA, anti-smooth muscle Ab, or anti–Liver Kidney Microsomal-1 Ab –  Other autoimmune disorders in 15-34%

•  Autoimmune thyroiditis, synovitis, celiac disease, and IBD

Differential Diagnosis: Autoimmune Hepatitis

Variable Cut-off Points

ANA or SMA ≥ 1:40 ≥ 1:80

1 2

SLA/LP or LKM-1 ≥ 1:80 2

IgG > ULN > 1.5x ULN

1 2

Liver histology Compatible Typical

1 2

No viral hepatitis 2

Autoimmune Hepatitis: Simplified diagnostic criteria

≥ 6 points: probable AIH ≥ 7 points; definite AIH

Hennes et al. Hepatology 2008

Druginducedtoxicity:NEWmedica+ons,Acetaminophen,salicylate,urinetoxicology(cocaine,ecstasy),an+bio+cs

Ischemic/hypoxicInjury:USDoppler

Autoimmunedisease:An+nuclearan+body(Ab),An+-SmoothMuscleAb,Gammaglobulins

Acuteviralhepa**s:An+-HAVIgM,An+-HBcIgM,HBsAn+gen(Ag)&DNAPCR,An+-HCV&RNAPCR,An+-HEIgM**Specialpopula*ons:CMV,EBV,HSV,ParvovirusB19,Adenovirus,Varicella,HHSV6

BiliaryObstruc*on:Alkphos,Directbilirubin,GGT,Ultrasound,MRCP

Wilson’sDisease:Serumceruloplasmin,copper.AlkPhos:TB&AST:ALT

Alcoholichepa**s:TotalbilirubinandPT/INR

100>1000s

Evalua+onofAcuteLiverInjury

•  PMH: –  Sjogren’s syndrome –  Hypothyroidism –  Breast cancer: partial mastectomy

with XRT –  Obesity

•  Meds: –  Levothyroxine 50 mcg –  Omeprazole 40mg daily –  Macrodantin 50mg QHS –  Simvastatin 40mg QHS

•  Social Hx: –  Married with two adult children –  EtOH use: minimal throughout

life –  IV or intranasal DU: never –  No tattoos, blood transfusions

•  Labs: –  Cr 0.8 –  Alb: 3.3/AST 584/ ALT 345/ AP 159/ TB

13 –  WBC 6.5/HgB 12.8/ Plt 234 –  INR 1.1

Case 1 Continued:

•  Lab results: –  Viral serology negative including

atypical viruses –  ANA: 1:320 –  ASMA: 1:320 –  IgG: 2.24 g/dL

•  Imaging: –  CT Abdomen: normal

appearing liver and spleen, no biliary dilation, no ascites

Case 1 Resolution:

Histology: The limiting plate of the portal tract is disrupted by a lymphoplasmacytic infiltrate

•  Liver Biopsy:

•  Treatment: –  Stop Macrodantin –  Prednisone 60mg daily x 1 week followed by taper –  Week 3: Consider Azathioprine 50 mg daily

Case 1 Resolution:

•  HPI: •  45 year old man with HTN presents

with abnormal liver tests for 5 years. •  Meds:

•  Losartan, HCTZ, Viagra, ASA, MVI, Simvastatin

•  Social History: •  EtOH: social •  Tobacco: 40 pack year Hx, quit 2010 •  Illicits: none

•  PE: •  BP: 152/80; BMI 37 •  Normal exam •  No spider angiomas, no nail changes, no

palmar erythema

•  Labs: –  Alb 4.6/AST 57/ALT 107/AP 73/TB

0.9; Hgb 13.5/Plt 283 –  Alpha one antitrypsin testing, TSH,

viral hepatitis, TTG IgA, fasting glucose were all normal/negative

–  Autoimmune panel: •  ANA: neg; ASMAb: 1:40; IgG: 1.41g

–  Iron studies: •  Ferritin 295; TSAT 40%

•  Imaging: –  RUQ US: Increased echogenicity

of the liver, normal spleen size

Clinical Case 2:

•  Additional Work-up: –  ? HFE mutation analysis

•  No sign of iron overload: –  Ferritin is <330 (patient is male) and TSAT is <45%

–  ? Liver biopsy to evaluate for autoimmune hepatitis •  ASMAb is mildly elevated while ANA is negative and IgG

level is normal: findings are non-specific and often found in NAFLD

–  NAFLD fibrosis score (NFS): •  0.013 (indeterminate)

Clinical Case 2:

1.  Do nothing, as so many Americans have fatty liver

2.  Immediate Fibroscan

3.  Immediate liver biopsy

4.  Stop statin

5.  Counsel patient on weight loss, recheck liver tests in 6 months, then consider liver biopsy/Fibroscan

Clinical Case 2: