Chapter 19. Hepatitis and Liver Disease

Hepatitis

Inflammation of the liver

Hepatitis A duration

acute, self-limiting illness

Hepatitis A transmission

fecal-oral (improper hand-washing, contaminated food/water)

What strains of hepatitis have a vaccine?

A and B, recommended for all adults

Hepatitis B transmission

blood, body fluid

Hepatitis C transmission

Blood

First-Line treatment for Hepatitis B

PEG-IFN

or

NRTI (e.g. tenofovir, entecavir)

How many HCV genotypes are there? Is treatment recommended for all of them?

6

yes

What is the first-line treatment for HCV?

Treatment-naive = DAA combo (2 to 3 with different MOAs)

Hepatitis B and C start as an acute illness but can lead to chronic symptoms such as...

chronic infection

cirrhosis

liver cancer

liver failure

death

Which vaccination is recommended for all adults?

Hep B

What is an alternative treatment option add-on for HCV if there is cirrhosis or post-treatment failure?

ribavirin

What medication is no longer recommended for HCV d/t success of DAAs?

Interferon alfa-based regimens

True or False - patients with HCV can be cured?

True

What medication regimens are recommended for all treatment-naive patients for all genotypes? (without cirrhosis/with compensated cirrhosis)

- Mavyret (glecaprevir/pibrentasvir) x 8 weeks

- Epclusa (sofosbuvir/velpatasvir) x 12 weeks

NS3/4A protease inhibitors

-previr (P for PI)

glecaprevir, grazoprevir, voxilaprevir

NS5A replication complex inhibitors

-asvir (a for NS5A)

elbasvir, ledipasvir, pibrentasvir, velpatasvir

NS5B Polymerase Inhibitors

-buvir (B for NS5B)

sofosbuvir

What is an important counseling point for protease inhibitors?

(-previr)

Take with food

Protease Inhibitors & Grub (PIG)

What is the boxed warning associated with all DAAs?

Risk of reactivating HBV

Test all pts for HBV before initiating DAA

Direct Acting Antiviral side effects

typically well-tolerated

some HA, fatigue, diarrhea, nausea

Which one of the first-line regimens should be taken with food due to having a protease inhibitor?

Mavyret (Glecaprevir/pibrentasvir)

sofosbuvir-containing regimens (i.e. epclusa, harvoni, vosevi) + amiodarone

serious symptomatic bradycardia risk, do not use together

True or false - sofosbuvir is effective alone as a treatment for HCV

false

What lab should be monitored with Zepatier (elbasvir/grazoprevir)?

ALT at or after 8 wks of tx

DAA + PSPORCS

avoid, decreased DAA concentration

What drugs should be dispensed in original container for HCV?

sovaldi, epclusa, harvoni, vosevi

epclusa, harvoni, vosevi antacids, h2ras, and ppis

Decreased concentrations of ledipasvir and velpatasvir

What drug should not be used with statins (SAL) and why?

Mavyret (glecaprevir/pibrentasvir)

risk of myopathy

True or false - ribavirin can be used as a monotherapy for HCV?

false

Boxed warnings for Ribavirin

1. Significant teratogenic effects (contraindicated in pregnancy)

2. monotherapy not effective for HCV

3. hemolytic anemia

How long after completion of ribavirin should pregnancy be avoided?

6-9 months after

What are the contreceptive requirements for taking ribavirin?

2 reliable forms of effective contraception required during treatment and post-treatment follow-up period

What is the treatment of choice for hepatitis B?

Nucleoside/tide reverse transcriptase inhibitors (NRTIs)

NRTI MOA

inhibit HBV replication by inhibiting HBV polymerase

True or false - NRTIs can be used as monotherapy for HBV?

true

Boxed Warnings associated with HBV NRTIs

- Lactic acidosis and severe hepatomegaly with steatosis (can be fatal)

- Exacerbations of HBV can occur upon discontinuation

Which DAA is an exception to taking with food?

Zepatier (elbasvir/grazoprevir) take without regard to food

At what renal function do HBV NRTIs need to be dose adjusted?

CrCl < 50 mL/min

What should patients be tested for prior to starting an NRTI for HBV?

HIV - some treat this

If patient co-infected, treat with 2 NRTIs to minimize risk of HIV antiviral resistance

TDF

Viread

(HBV)

TAF

Vemlidy

(HBV)

Entecavir

Baraclude

(HBV)

What NRTIs are preferred therapy for HBV?

- Viread (TDF)

- Vemlidy (TAF)

- Baraclude (Entecavir)

Lamivudine

Epivir HBV

What is the boxed warning associated with Epivir HBV?

Do not use for treatment of HIV (HBV has lower dose of lamivudine and can lead to resistance for HIV)

Side effects of lamivudine?

HA, NVD

Warnings for TDF and TAF

- renal toxicity (more w TDF)

- Fanconi syndrome

- Decreased BMD

Side effects of TDF and TAF

N/D

Lipid abnormalities (more with TAF)

What drugs should be dispensed in original container for HBV?

Vemlidy, Viread

Boxed Warning associated with Adefovir (Hepsera)?

Caution in patients w/ renal impairment or those at risk of renal toxicity (concurrent nephrotoxic drugs/NSAIDs)

What drugs should not be used with adefovir?

Tenofovir formulations (inc risk of virologic failure and ADEs)

What is an approved monotherapy for HBV other than NRTIs? ROA?

Pegylated interferon alfa

subucutaneous

Why is the interferon alfa pegylated?

to prolong half-life

Boxed Warnings associated with Peg Ifn alfa

- Neuropyschiatric

- autoimmune

- ischemic

- infectious

disorders

Side effects associated with PegIFN alfa

- CNS (fatigue, depression)

- GI upset

- Inc LFTs (5-10x ULN)

- flu-like syndrome (fever, chills, HA, malaise) -> pre-tx with acetaminophen and an antihistamine

- myelosuppression

Cirrhosis

advanced fibrosis (scarring) of liver that is usually irreversible

Most common causes of cirrhosis?

hep c

alcohol

What is a common clinical presentation associated with cirrhosis?

Yellow skin/eyes (jaundice)

What LFTs are affected in acute liver toxicity, including from drugs?

increased AST/ALT

What LFTs are affected in chronic liver disease (i.e. cirrhosis)?

- Increased AST/ALT, alk phos, TBili, LDH, PT/INR

- Decreased albumin

LFTs affect in alcoholic liver disease

- Both increased AST and ALT, but AST will be about double ALT (AST>ALT)

- Increased GGT

LFTs affected in hepatic encephalopathy?

increased ammonia

LFTs affected in jaundice?

increased Tbili

Child-pugh Classification System

Assess severity of liver disease

5-15 score (severe is 10 to 15)

What natural product is a known hepatotoxin?

kava

What natural product may be used by those with liver disease but has limited data for help or harm? (may interact w/ DAAs)

milk thistle

What key drugs have a boxed warning for liver damage?

Acetaminophen *high doses, acute or chronic*

Amiodarone

Isoniazid

Ketoconazole

Methotrexate

Nefazodone

Nevirapine

PTU

VPA

Zidovudine

AAm I Knowing My NaNa PaVeZ?

Bosentan

Felbamate

Flutamide

Leflunomide and teriflunomide

Lomitapide

Maraviroc

Tipranavir

Tolcapone

When should a hepatotoxic drug be discontinued?

When LFTs >3x the ULN

What pain reliever is preferred in those with cirrhosis (with adjusted dosing)?

acetaminophen (even though it is a known hepatotoxin)

NSAIDs should not be used can lead to decompensation, including bleeding

Chronic alcohol ingestion over a long period of time causes...

steatosis (Fatty liver)

May progress to alcoholic hepatitis, fatty liver (steatohepatitis), or chronic hepatitis if drinking continued

What drugs are used to control alcohol withdrawal symptoms?

BZDs

What drugs are used to prevent relapse of alcohol?

- Naltrexone (vivitrol)

- Acamprosate

- Disulfiram (formerly antabuse)

What is used to treat/prevent Wernicke-Korsakoff syndrome for alcohol-associated disease?

thiamine

diseases cause by brain damage by a lack of vitamin b-1

Portal HTN

When BF is restricted in the liver d/t fibrotic tissue, causing increased BP in portal vein = blood backing up and flowing into smaller vessels = ballooned vessels

What are ballooned vessels from portal htn called?

esophageal varices (risk of breaking open and bleeding)

Mechanical options for variceal bleeds (immediate tx. to stop bleed)

band ligation - band around vessel

sclerotherapy - solution injected into vessel to collapse/close

Medications that vasoconstrict splanchnic (GI) circulation

Octreotide (selective for splanchnic vessels)

Vasopressin (non-selective, NOT first line)

What medication can be used for primary and secondary prevention of variceal bleeding?

Non-selective BBs; decrease portal pressure by constricting splanchnic vessels (less inflow)

Nadolol (Corgard)

Propranolol (Inderal LA, Inderal XL)

Propranolol

Inderal LA/XL

Nadolol

Corgard

Octreotide

Sandostatin

Octreotide side effects

bradycardia, cholelithiasis, biliary sludge

Vasopressin MOA

antidiuretic hormone analog

BB Boxed Warnings

Do not discontinue abruptly, taper dose over 1-2 weeks

BB Warnings/SEs

- Can worsen/mask hypoglycemia

- Caution with asthma/COPD

- Caution with Raynaud's (exacerbation)

- Bradycardia

- Hypotension

- CNS effects (e.g. fatigue, dizzy, depression)

-> propranolol worse d/t lipophilicity and crossing BBB

- impotence

- monitor HR (goal 55-60)

Symptoms of Hepatic Encephalopathy

- Musty breath odor

- Changes in thinking/confusion/forgetfulness

- Asterixis (flapping hand tremor)

Why do the symptoms associated with hepatic encephalopathy occur?

accumulation of gut-derived nitrogenous substances in blood (ammonia)

Non-Pharm tretment of hepatic encephalopathy

diet (limit protein, especially animal)

Treatment for Hepatic Encephalopathy

- Lactulose (non-absorbable disaccharide)

- Abx (rifaximin)

Lactulose is first line for...

acute and chronic (prevention) therapy for hepatic encephalopathy

Lactulose MOA

converts ammonia produced by intestinal bacteria to ammonium, which is polar and does not diffuse into blood

Add on treatment for hepatic encephalopathy

Rifaximin

Boxed warnings associated with neomycin

Neurotoxicity (hearing loss, vertigo, ataxia)

Neomycin side effects

GI upset

Lactulose side effects

flatulence, diarrhea, dyspepsia, abdominal discomfort

Lactulose monitoring

bowel movements, ammonia

What can ascites lead to?

Spontaneous bacterial peritonitis (SBP)

Hepatorenal syndrome (HRS)

How should patients with cirrhosis and ascites be treated?

Consider transplant