Common Misconceptions in - PowerPoint Presentation

Slide1

Common Misconceptions in Liver Disease and Cirrhosis

Justin Mitchell, DO, MS

Assistant Professor

Rush University Medical Center

SGNA

10/20/2018Slide2

No disclosures.Slide3

Objectives

Identify abnormal liver chemistries.

Recognize medications that may lead to harm in patient's with advanced liver disease.

Recognize "taboo" medications that may actually be useful in patient's with advanced liver disease.

Identify other potential factors that may lead to worsening liver related issuesSlide4

54

yo

M presented to his PCP for an annual check-up. Lab work found an

AST

37

and an ALT

43 (Normal range 12-45). All other labs normal. He has no past medical history and no complaints. Are you worried about this patient’s LFTs?

4Slide5

Misconception: LFTs are only abnormal if they’re out of the normal range.

How are normal ranges obtained?

Why is the upper limit of normal (ULN) for ALT at Rush 40 U/L but at the VA it is 75 U/L?

5Slide6

Normal ranges are established by taking a “normal, healthy” population of patients and having their blood is drawn.

6

A mean is established after significant outliers are removed.

Lower limit of normal (LLN)

and ULN

are

two standard deviations in either direction. Slide7

Abnormal levels are then usually defined as

a value exceeding the

ULN.

However, the

reference limits for each test often vary among

laboratories.

7Slide8

So, why the discrepancy?

Some “normal”

patients

will have levels above the ULN.

8

LFTs

2%

98%Slide9

So, why the discrepancy?

Some “healthy”

patients

may have unknown

chronic hepatitis C

infection.

45-85% of patients with HCV are unaware

9

HCV

Ward JW.

The epidemiology of chronic hepatitis C and one-time hepatitis C virus testing of persons born during 1945 to 1965 in the United States

.

Clin

Liver Dis. 2013. 17(1):1-11.

Denniston

et al. Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C:

National Health and Nutrition Examination Survey 2001-2008

. Hepatology. 2012. 55(6):1652-61.Slide10

So, why the discrepancy?

Ranges were established before the discovery of NAFLD.

10Slide11

So, is there a normal range?

Population study which

excluded people at risk for

NAFLD, concluded

that the “healthy range” for serum ALT should be up

to:

30

U/L for

men.

19

U/L for

women.

ACG guidelines now define a normal health serum ALT level

33 IU/L for men.

25 IU/L for women.

Some have argued that this will lead to

unnecessary medical

expenditures.

However, large

population studies in Korea have demonstrated

increased prevalence of

NAFLD

and

increased liver-related mortality

in middle aged adults with

ALT levels between 20 and 40

U/L compared to those with ALT < 20

U/L

11

Prati

.

Ann Intern Med. 2002;137:1–9

.

Kim.

BMJ. 2004;328:983.Slide12

Take Home

Women and men with elevations in their ALT >20-30 respectively should be considered for evaluation for underlying liver disease.

12Slide13

64

yo

W was found to have an AST 33 and an ALT 42. All other lab work is normal. She has a past medical history significant for diabetes, HTN, and elevated triglycerides. No alcohol. An abdominal ultrasound notes increased echogenicity consistent with fatty infiltration or hepatocellular disease.

Should we just continue to monitor this patient’s LFTs?

13Slide14

Misconception: Fatty liver is nothing to worry about

14Slide15

Fatty Liver: NAFLD/NASH

Most common liver disease:

affects 20-45% of U.S. population

Relationship to obesity epidemic and metabolic syndrome.

May progress to cirrhosis and hepatocellular carcinoma (HCC).

15Slide16

7%

31%

62%

75%

0

20

40

60

80

100

Patients with NASH (%)

Both Diabetes and HT (n = 11)

Association Between NASH, Type 2 Diabetes,

and Hypertension in 108 Severely Obese*

* BMI > 30

Dixon. Gastroenterology.

2001;121:91-100.

Neither Diabetes nor HT (n = 57)

Diabetes Alone (n = 8)

Hypertension Alone (n = 29)

A combination of 2 of these predictors allows

a sensitivity of 0.8 and specificity of 0.89 for NASHSlide17

Importance

of staging fibrosis in NAFLD

Fibroscan

, MRE

17Slide18

NAFLD: stage 3-4 fibrosis have worse outcomes then stage 1-2.



More

aggressive treatment plans

18

Le

MH

et al.

Prevalence

of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States. PLOS

ONE. 2017. 12(3

): e0173499

.Slide19

Multi disciplinary approach: metabolic disorder clinic, training in obesity medicine, motivational interviewing, frequent follow-up

visits

Diet, exercise, medications for weight

loss,

control of comorbid conditions

Improves

ALT, steatosis, fibrosis, cardiovascular system

19

Vilar-

Gomez

et

al. Weight Loss Through

Lifestyle Modification

Significantly Reduces Features of Nonalcoholic

Steatohepatitis. Gastroenterology 2015;149:367-378.Slide20

Clinical trials

20Slide21

Testing for other concomitant liver diseases

21Slide22

Take Home

Fatty liver disease is a “big deal”

Staging of the underlying liver disease and a multidisciplinary approach is key

Clinical trials are available

Evaluate for other underlying liver diseases

22Slide23

A 60

yo

W who is a nun presents to your office for a routine visit. Her lab work, including her LFTs, are completely normal. As you reach for the door knob to leave, she casually asks about HCV testing because she saw “one of those

Harvoni

commercials”. What is the your most appropriate response?

Roll your eyes, huff, and pretend you didn’t hear her

.

No testing is necessary given her normal LFTs and lack of risk factors.

Obtain a HCV RNA and HCV genotype.

Test her for HCV antibody.

23Slide24

Misconception: I don’t need to test my patients for HCV if their LFTs are normal.

24

Armstrong

et al. The

prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-14.

HCV prevalence analyzed during two

time periods

: 1988-1994 and 1999-2002Slide25

Undiagnosed HCV remains a huge issue for Illinois as well as the U.S. as a whole.

Perhaps as many as 45-85% of HCV infected people do not know they are infected.

Expanded screening is cost effective

Well tolerated, highly effective antiviral treatments available

25

Denniston

et al.

Awareness

of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008. Hepatology. 2012. 55(6):1652-61

.

Rein et al.

The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings

. Ann Intern Med. 2012. 156(4):263-70.Slide26

Take Home

Recommendations for birth cohort screening for HCV.

The U.S. Preventive Services Task Force (USPSTF) and CDC recommend that physicians not only routinely screen high-risk adults, but also offer a one-time screening to all adults born between 1945 and 1965.

Anyone born between

1945-1965

regardless of risks or normal LFTs.

26Slide27

72

yo

M has hemochromatosis with progression to cirrhosis. His liver disease is well compensated and he does not drink alcohol. He has been struggling with osteoarthritis and would like to take something for his pain. What would be your first recommendation for a pharmacologic treatment to help control his pain?

Hydrocodone/acetaminophen

Ibuprofen

Acetaminophen

Oxycodone

Tramadol

27Slide28

Misconception: Patients with cirrhosis should avoid acetaminophen.

Acetaminophen is the leading cause of

acute liver failure

in the United States.

28

*Slide29

Misconception: Patients with cirrhosis should avoid acetaminophen.

Creates

the perception that it is dangerous for patient’s with

chronic liver disease

.

Many practitioners are not willing to prescribe acetaminophen to patient’s with liver disease.

In the

general

population, only concerns for safety at a maximal dose of 4g per day in the .

29

Larson. Hepatology. 2005;42(6):1364-1372Slide30

The half life or acetaminophen in cirrhotic patient’s is double the that of healthy controls.

However, hepatic injury remains rare when the dosage is limited to < 4g/d.

30

Pezzano

.

Presse

Med. 1988;17(1):21-24.

Mofredj

. Ann Med Interne. 1999;150(6):507-511.

Villeneuve. Gastro

Clin

Biol. 1983;5(2):898-902.Slide31

Metabolism of acetaminophen

31Slide32

Metabolism of acetaminophen

32

Glutathione stores have not been found to be depleted in cirrhotic patient’s

.

Benson. Am J

Ther

. 2005;42(6):133-141.Slide33

Supportive Studies

A small double blinded crossover

20 patients with liver disease

Acetaminophen 4 g/d for 13 days

No adverse effects

Small case control study

Alcohol related cirrhosis

3 g/d acetaminophen

No acute

deceompensation

.

Few other studies found it safe for short-term use of acetaminophen in chronic liver disease.

33

Heard. Aliment

Pharmacol

Ther

. 2007;26(2):283-290.

Lucena

.

Eur

J

Clin

Pharmacol

. 2003;59(1):71-76.

Benson. Am J

Ther

. 2005;12(3):131-144.Slide34

Take Home

American Liver Foundation and FDA issued

recommendations to not exceed

2-3 g/d of acetaminophen

in patient’s with chronic liver disease.

To be safe, err on the side of caution:

NO more the 2 g/d

of acetaminophen in patient’s with chronic liver disease.

34Slide35

72

yo

M has hemochromatosis with progression to cirrhosis. His liver disease is well compensated and he does not drink alcohol. He has been struggling with osteoarthritis and would like to take something for his pain.

The patient tried acetaminophen but it was not effective at controlling his pain. Which of the below medications would you definitely want to avoid in this patient?

Hydrocodone/acetaminophen

Ibuprofen

Oxycodone

Tramadol

35Slide36

Misconception: Patients with cirrhosis can safely take NSAIDs.

Given the concerns for acetaminophen use in chronic liver disease, many practitioners turn to NSAIDs.

NSAIDs: metabolized by CYP enzymes and are mostly bound to albumin.

Cirrhosis: decreased CYP activity and impaired production of albumin

Altered metabolism and bioavailability increase serum levels.

36

Schoene

.

Eur

J

Clin

Pharmacol

. 1972;4(2):56-73

Williams.

Eur

J

Clin

Pharmacol

. 1984;27(3):291-296.Slide37

37

NSAIDs

COX 1/2

PGE 2

PGI 2

Sodium Retention

- Edema

- Ascites

Decreased renal perfusion

- Acute kidney injury

-

Hepatorenal

syndrome

Adverse events of NSAIDs in cirrhosisSlide38

Adverse events of NSAIDs in cirrhosis

Reduce renal perfusion.

Reduced prostaglandin induced renal vasodilation

Reduced renal blood

flow and renal dysfunction.

AKI, HRS

Reduced sodium

/ water excretion

.

Peripheral edema, ascites

38

Arryo

. Am J Med. 1986;81(2B):104-122.Slide39

39

NSAIDs

COX 1/2

Prostaglandins

Decreased

GI mucosal

protection

Reduce pain, inflammation, fever

Prostaglandins

Decreased platelet aggregation,

thrombocytopenia

Thromboxane

Adverse events of NSAIDs in cirrhosis Slide40

Adverse events of NSAIDs in cirrhosis

GI mucosal side effects.

Decreased platelet aggregation.

Thrombocytopenia.

40

Peck. Aliment

Pharmacol

Ther

. 2007;26 Suppl1:21-28.Slide41

Adverse events in cirrhosis

Correlation between NSAIDs and first variceal bleeding episode.

41

De

Ledinghen

. Gut. 1999;44(2):270-273.Slide42

Take Home

Avoid NSAIDs in patients with cirrhosis.

42Slide43

6

2

yo

AA M presents to your office for a routine follow-up visit. He has compensated ETOH cirrhosis as well as HTN. He has been abstinent from alcohol for 5 years. Lab work is concerning for elevated total cholesterol and LDL with low HDL. He has a family h/o of CV events and smokes. Besides lifestyle modification, what pharmacologic treatment would be the most useful in this patient?

Statins

Fenofibrates

Cholestyramine

Fish oil

Red rice yeast

43Slide44

Initial trials and postmarketing reports of statins

found

many patients

with

mild elevations in

liver chemistries.

C

oncern about potential hepatotoxicity given that statins are

hepatically

cleared.

Prescribers wary about giving to patients with underlying liver disease.

A meta-analysis 50,000

patients

no

difference in

liver chemistries when comparing statins with placebo.

44

Misconception: Patients with liver disease/ cirrhosis should not take statins.

Demyen

.

Clin

Liver Dis. 2013;17(4):

699–714.

Law. Am J

Cardiol

. 2006;97(8A):

52C–60C.Slide45

Nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk

greater

than that conferred by the conventional risk factors.

45

Cardiovascular disease is as common in patients with chronic liver disease.

Giovanni et al. Risk

of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver

Disease. NEJM. 2010. 363:1341-1350.Slide46

Cardiovascular disease is an important cause of morbidity and mortality in this population.

Need for aggressive treatment with lipid-lowering agents such as statins.

Assessment

of statin safety by the Liver Expert

Panel suggested

that statins are generally well tolerated in patients with chronic liver disease

NAFLD

, primary biliary cirrhosis, and hepatitis C virus.

These

drugs also appear to be safe in patients with stable/compensated cirrhosis.

46

Tandra

. Current Treat Options

Cardiovasc

Med. 2009;11(4

):

272-8.Slide47

Statins should be avoided in:

Decompensated

cirrhosis

Acute liver failure

47Slide48

Statins and prevention of decompensation

48

Kamal. Am J

Gastroenterol

. 2017;112(10):1495-1505.Slide49

Prevention of Fibrosis Progression

49Slide50

Statins and mortality in chronic liver disease

50Slide51

Statin Conclusions

Statins may:

Slow

the progression of hepatic fibrosis.

Prevent hepatic decompensation in cirrhosis.

Reduce all-cause mortality in patients with chronic liver disease

.

Reduce portal hypertension.

Reduce the risk for HCC.

More research is needed before prime time.

51

Kamal. Am J

Gastroenterol

.

2017;112(10

):

1495-1505.

Kim.

Clin

Gastoenterol

Hepatol

.

2017;15(10

):

1521-1530

Vargas.

Curr Gastroenterol Rep. 2017;19(9):43. Slide52

Take Home

In most cases, the

benefit of statins in patients with underlying liver disease who are candidates for statin therapy outweighs the risk of the very rare event of serious liver injury.

52Slide53

37

yo

W with alcohol related cirrhosis comes to your office complaining of RUQ abdominal pain, described as sharp and stabbing, and made worse with eating fatty meals. An abdominal ultrasound notes gallstones and a cirrhotic appearing liver with trace

perihepatic

ascites. What would be the next appropriate management step?

Proceed with elective cholecystectomy

Repeat an ultrasound in 6

months

Watchful waiting

Start

ursodiol

53Slide54

Misconception: Surgery is safe in cirrhosis.

Increased

risk

of bleeding, infection, liver decompensation, liver failure, and morbidity/mortality following surgery.

Montomoli

et al.

Coexisting Liver Disease Is Associated with Increased Mortality After Surgery for Diverticular

Disease. Dig Dis Sci. 2015. 60(6):1832-40.

http://www.webaisf.org/media/12244/11_fagiuoli_.pdf

Mortality Post elective Surgery

(Normal, Cirrhosis, Cirrhosis +PHTN)Slide55

Patients with risk factors for liver disease or cirrhosis should be evaluated carefully prior to any

surgery

Risk Stratification

CTP

MELD

Mayo calculator

Determine

the risk of post-operative mortality for all types of major surgery, especially

gastrointestinal

, orthopedic and cardiac

surgery.

Does not factor in other co-morbid conditions, prior medical history, or surgical experience.

55Slide56

56

https://www.mayoclinic.org/medical-professionals/model-end-stage-liver-disease/post-operative-mortality-risk-patients-cirrhosisSlide57

Take Home

Elective surgery is risky in patients with cirrhosis.

Evaluation of post operative mortality/morbidity and discussion of the risks should be performed before proceeding with elective surgery.

57Slide58

46

yo

W with PBC and NASH presents to your office for a routine follow-up visit. She was previously found to have stage 2 fibrosis on her biopsy. She inquires about alcohol use. What would be the most appropriate recommendation?

Binging is safe as long as she doesn’t drink more then 5 drinks at one sitting.

Avoid alcohol completely.

Mild alcohol use (1 drink/day) is acceptable.

Wine and beer is okay but she should avoid hard liquor drinks

.

58Slide59

Misconception: “My liver disease isn’t from alcohol doc… so I can still drink , right?”

A common misconception among patients.

But believe

it or

not, there

has been conflicting evidence with regards to

alcohol intake and chronic liver disease.

59Slide60

Modest

alcohol consumption may reduce the risk for cardiovascular

mortality.

NAFLD has high cardiovascular risk.

Should moderate alcohol consumption be

allowed

in this population?

The odds of NASH decreased as the frequency of alcohol consumption increased within the range of modest consumption.

Modest

drinkers also had significantly lower odds for

fibrosis.

60

Dunn. Journal

of

Hepatology. 2012;57(2):384–391

. Slide61

Heavy

alcohol consumption

many

harmful effects

(CV, malignancy, injury,

etc

) including

those on liver

should

be discouraged regardless whether an individual has NAFLD or

not.

It is

not known if cardiovascular and metabolic benefits of light to moderate alcohol consumption

seen in the

general population are extended to those with

NAFLD.Studies that suggest moderate alcohol use may have hepatic benefits are

largely

cross-sectional in

nature.

Need further prospective studies

U

ntil

further

studies

become

available, individuals

with NAFLD should avoid consuming alcohol of any type or amount.

61

Liangpunsikal

. Am J

Gastroenterol

. 2012; 107(7):976-978.

Slide62

Current consensus is that even

mild to moderate alcohol use a few times a week

can potentially

lead to ongoing

damage or fat deposition.

Patients

aren’t always truthful about their

quantity of alcohol intake.

May lead

to decompensation

Variceal bleeding, ascites, encephalopathy

62Slide63

Take Home

All patients with chronic liver disease or cirrhosis, no matter what the underlying etiology, should avoid alcohol.

63Slide64

Summary of Take Home Points

ULN for ALT ~20 U/L for women and ~30 U/L for men.

Fatty liver disease is abundant and multi disciplinary care is important.

Test for HCV in patients born between 1945-1965 even without risk factors

< 2 g/d of acetaminophen in cirrhotic patients is okay.

Avoid NSAIDs in cirrhosis.

Statins may be used in patient’s with chronic liver disease and may have more benefits then previously known.

Surgery is risky in cirrhosis.

Avoid alcohol in chronic liver disease.

64Slide65

Questions??

Justin Mitchell:

Office: (312) 563-1180

Cell: (217

) 390-6717

justin_mitchell@rush.edu

Clinics and Endoscopy at RUMC and ROPH

Multiple other locations in and around Chicago

Transplant

new referrals – 312-942-LIVE

65Slide66

Thank you!

RUSH Liver Team