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LIVER Flashcards

LIVER

1
Q

Hepatitis means inflammation of the liver and it’s cause by?

A

Hepatitis Virus but also

Alcohol

Drugs

Autoimmune Disease

Herpesvirus

CMV Epstein Virus

Adenovirus

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2
Q

Describe Hepatitis A?

A

Acute (self limiting illness)

Fecal-Oral Transmission (through improper hand washing or via contaminated food/water)

Vaccine Available

First Line Treatment: SUPPORTIVE CARE

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3
Q

Describe Hepatitis B?

A

Acute and Chronic (acute can lead to chronic infection, cirrhosis, cancer, liver failure and death)

Blood and Body Fluids Transmission (sex, needle, perinatal)

Vaccine Available

First Line Treatment: PEG-INF (Pegylated Interferon or NRTI (Tenofovir or Entecavir)

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4
Q

Describe Hepatitis C?

A

Acute and Chronic (acute can lead to chronic infection, cirrhosis, cancer, liver failure and death)

Blood and Body Fluids Transmission (sex, needle, perinatal)

NO Vaccine Available

First Line Treatment:

-NAIVE PT:

DAA ( Direct Acting Antiviral) Combination

-SELECTED PT:

DAA ( Direct Acting Antiviral) Combination + RBV (Ribavirin)

DAA ( Direct Acting Antiviral) Combination +RBV (Ribavirin) +PEG-INF (Pegylated Interferon)

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5
Q

How many types of Genotype does the Hepatitis C have?

A

6 genotype ( 1–6)

Various Subtypes ( 1a or 1b)

Treatment and Duration depends on genotype, presence of Cirrhosis and pt treatment history.

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6
Q

What’s the PREFFERED Hepatitis C (HCV) Treatment REGIMEN of treatment NAIVE patient WITHOUT Cirrhosis ?

A
  • 2 to 3 Direct Acting Antiviral (DAAs) with DIFFERENT MECHANISMS of ACTION usually for 12 WEEKS ( some 8 Weeks in appropriate pt).
  • Some combination includes: RITONAVIR which is NOT ACTIVE for HCV but USED to BOOST LEVELS of HCV protease inhibitors used with it.

RITONAVIR can be ADDED to DAA as an alternative treatment option.

INTERFERON are NOT RECOMMENDED but could be USED if DAA are CONTRAINDICATED or TOO Expensive.

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7
Q

PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?

A

MOA : NS3/4A Protease Inhibitor

PREVIR : P for PI

DRUGS:

Grazo-PREVIR

Parita-PREVIR

Sime-PREVIR

Voxila-PREVIR

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8
Q

PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?

A

MOA: NS5A Replication Complex Inhibitor

ASVIR: A for NS5A

DRUGS:

Daclat-ASVIR

Ledip-ASVIR

Ombit-ASVIR

Pibrent-ASVIR

Velpat-ASVIR

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9
Q

PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?

A

MOA: NS5B Polymerase Inhibitor

BUVIR: B for NS5B

DRUGS:

Dasa-BUVIR

Sofos-BUVIR

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10
Q

Why are Direct Acting Antiviral (DAA) TREATMENT IMPORTANCE IN HCV?

A

DAA have revolutionized HCV treatment and replace older treatment( lnterferon and Ribavirin) and offer CURE for MOST patients.

Consist of DRUG COMBO that TARGET DIFFERENT PHASES of the HCV LIFE CYCLE.

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11
Q

Direct Acting Antiviral (DAA) Treatment Regimen should consist of 2 DIFFERENT MECHANISMS of ACTION?

A

Preffered: Daclat-ASVIR + Sofos-BUVIR

Not Preffered: Dasa-BUVIR + Sofos-BUVIR

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12
Q

What IMPORTANT to REMEMBER about PROTEASE Inhibitors used for HCV and HIV?

A

Take with food (Almost All)

PI(G) : PIG and FOOD

Except:

Elb-ASVIR/Grazo-PREVIR (Zepatier) : Without Regard to Food

Fosamprenavir Oral Suspension: Without Food in Adult

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13
Q

What’s the Box Warning for ALL class of DAA (Direct Acting Antiviral) Drugs?

A

*Risk of REACTIVATING HBV; test all patients for HBV before starting a DAA.

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14
Q

What’s the Warning for SOFOS-BUVIR Containing Regimen?

A
  • Serious Symptomatic BRADYCARDIA reported when taken with AMIO-DARONE.
  • DO NOT use Amiodarone with SOFOS-BUVIR or SOFOS-BUVIR Containing Regimen.
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15
Q

What’s are the SIDE EFFECTS of ALL class of DAA (Direct Acting Antiviral) Drugs??

A

*Well Tolerated;

Head ache

Fatigue

Diarrhea

Nausea

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16
Q

What’s the MONITORING of ALL class of DAA (Direct Acting Antiviral) Drugs?

A

LFT ( Including Bilirubin)

HCV-RNA

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17
Q

What’s are the Drug INTERACTION of ALL class of DAA (Direct Acting Antiviral) Drugs?

A

*SIGNIFICANT Drug INTERACTION Potential.

See package insert of each agent for more details.

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18
Q

What’s are the CONTRAINDICATIONS of ALL class of DAA (Direct Acting Antiviral) Drugs?

A

*CONTRAINDICATIONS with strong INDUCERS of CPY3A4 example:

Car-bama-zepine

Ox-carba-zepine

Phe-no-barbital

Phe-ny-toin

Ri-fam-pin

Rifa-butin

St. John’s Worth

*Most DAA’s INCREASE concentration of STATINS and INCREASE risk of Myopathy.

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19
Q

Sofos-BUVIR

So-Val-Di

A

SOVALDI

Serious Drug INTERACTION

  • Monotherapy Not Recommended
  • Dispense in ORIGINAL Container: ( Applies to all Sofos-BUVIR containing COMBINATION)
  • AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametime , PPI) during treatment.

Use Less Than or Equal to 40 mg Famotidine BID or Equivalent

APPROVED FOR:

Children greater than 12 Years Old with CERTAIN Genotypes

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20
Q

*Sofos-BUVIR/ Ledip-ASVIR

Har-Vo-Ni

A
  • HARVONI
  • Dispense in ORIGINAL Container
  • AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at the sametime , PPI) during treatment.

Use Less Than or Equal to 40 mg Famotidine BID or Equivalent

APPROVED FOR:

HCV/HIV Co-Infection

Children greater than 12 Years Old with CERTAIN Genotypes

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21
Q

*Sofos-BUVIR/ Velpat-ASVIR

Ep-Clu-Sa

A
  • EPCLUSA
  • Dispense in ORIGINAL Container
  • AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametime , PPI) during treatment.

Use Less Than or Equal to 40 mg Famotidine BID or Equivalent

*DO NOT Use PPI with EPCLUSA

APPROVED FOR:

Pan-Genotypic (ALL 6 HCV genotype) in treatment NAIVE Pt

HCV/HIV Co-Infection

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22
Q

Sofos-BUVIR/ Velpat-ASVIR/ Voxila-PREVIR

Vo-Se-Vi

A

*VOSEVI

Take with FOOD

  • Dispense in ORIGINAL Container
  • AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametimrle , PPI) during treatment.

Use Less Than or Equal to 40 mg Famotidine BID or Equivalent

APPROVED FOR:

Salvage Therapy ( FAILED previous therapy)

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23
Q

Sofos-BUVIR/ Velpat-ASVIR/ Voxila-PREVIR

Vo-Se-Vi

A

*VOSEVI

Take with FOOD

  • Dispense in ORIGINAL Container
  • AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametimrle , PPI) during treatment.

Use Less Than or Equal to 40 mg Famotidine BID or Equivalent

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24
Q

Gleca-PREVIR/ Pibrent-ASVIR

Ma-Vy-Ret

A

*MAVYRET

Take with FOOD

APPROVED FOR:

Pan-Genotypic (ALL 6 HCV genotype) in treatment NAIVE Pt.

Salvage Therapy ( FAILED previous therapy)

8 Week Course ( SELECTED PT)

HCV/HIV Co-Infection

CONTRAINDICATIONED with Efavirenz , Cyclosporine, Ethinyl Estradiol products, and HIV Protease Inhibitor s ( ataza-NAVIR, Daru-NAVIR, Lopi-NAVIR, Rito-NAVIR)

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25
Q

Which DAA DRUGs are APPROVED FOR:

PAN- GENOTYPIC (ALL 6 HCV genotype) in treatment NAIVE Patients.

A

Epclusa

Mavyret

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26
Q

Which DAA Drugs are APPROVED FOR:

SALVAGE THERAPY ( FAILED previous therapy)

A

Vosevi

Mavyret (selected pts)

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27
Q

Which DAA DRUGS is APPROVED FOR:

8 WEEKs Course of Therapy ( SELECTED PT)

A

Mavyret

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28
Q

Which DAA DRUGS are APPROVED FOR:

HCV/HIV Co-Infection

A

Epclusa

Harvoni

Mavyret

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29
Q

Which DAA DRUGS are APPROVED FOR:

Children GREATER THAN 12 Years Old with CERTAIN Genotypes

A

Sovaldi

Harvoni

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30
Q

Acid Suppressive Therapy (ANTACIDs, H2RAs, PPI) should be AVOIDED OR MINIMIZED in these DAA DRUGS:

A

SOVALDI (Sofos-BUVIR )

HARVONI (Sofos-BUVIR/Ledip-ASVIR): Decrease concentration of Ledip-ASVIR)

EPCLUSA (Sofos-BUVIR/Velpat-ASVIR) : Decrease concentration of Velpat-ASVIR

VOSEVI (Sofos-BUVIR/Velpat-ASVIR/ Voxila-PREVIR) : Decrease concentration of Velpat-ASVIR

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31
Q

Daclat-ASVIR

Dak-Lin-Za

A
  • DAKLINZA
  • Combined with Sofos-BUVIR
  • Monotherapy NOT Recommended

CONTRAINDICATIONS: CYP450 3A4 Inducers

Consider screening for NS5A polymorphism if patient has HCV genotype 1A with CIRRHOSIS

32
Q

Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR

Tech-Ni-Vie

A
  • TECHNIVIE
  • Take with FOOD

*CONTRAINDICATIONS:
Moderate Severe Hepatic Impairment (Child Pugh B or C)

DO NOT use with drugs HIGHLY DEPENDENT ON CYP3A4 for Elimination ( INCREASE Level can cause Adverse Event)

DO NOT use with MODERATE to STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.

DO NOT use with RIBAVIRIN in COMBINATION REGIMENS

  • WARNING: Hepatic Decomposition and Hepatic Failure in patients with CIRRHOSIS; risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED Risk.
  • SIGNIFICANT DRUG INTERACTION POTENTIAL
  • Risk of HIV PROTEASE INHIBITOR RESISTANCE

Side Effect:

Insomnia

Pruritus

33
Q

Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR + Dasa-BUVIR

Vie-Ki-Ra XR/Pak

A
  • VIEKIRA
  • Take with FOOD
  • Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR ; take ONCE daily in am
  • Dasa-BUVIR:take TWICE daily with FOOD
  • VIEKIRA XR: Take ONCE daily with meal

*CONTRAINDICATIONS:
Moderate Severe Hepatic Impairment (Child Pugh B or C)

DO NOT use with drugs HIGHLY DEPENDENT ON CYP3A4 for Elimination ( INCREASE Level can cause Adverse Event)

DO NOT use with MODERATE to STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.

DO NOT use with STRONG INDUCERS or INHIBITORS of CYP2C8 (Ex. Gemfibrozil); Dasa-BUVIR is a major. CYP2C8 substrate

DO NOT use with RIBAVIRIN in COMBINATION REGIMENS

  • WARNING: Hepatic Decomposition and Hepatic Failure in patients with CIRRHOSIS; risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED Risk.
  • SIGNIFICANT DRUG INTERACTION POTENTIAL
  • Risk of HIV PROTEASE INHIBITOR RESISTANCE
  • Side Effect:

Insomnia

Pruritus

34
Q

TECKNIVIE and VIEKIRA are CONTRAINDICATED with STRONG CYP3A4 INDUCERs along with

A
  • Ethinyl Estradiol Products ( Lo Loestrin FE, Norinyl, Ortho Tri Cyclen Lo, Xulane, NuvaRing, Femhr: hormone replacement therapy)
  • Lovastatin
  • Simvastatin

Alfuzosin, Colchicine, Ranolazine, Dronedarone, Lurasidone, pimozide, Ergotamine Derivative s, Efavirenz, Sildenafil, Triazolam, and Oral Midazolam

35
Q

Elb-ASVIR/ Grazo-PREVIR

Ze-Pa-Tier

A

*ZEPATIER

*CONTRAINDICATIONS:
Moderate to Severe Hepatic Impairment (Child Pugh B or C)

DO NOT use with STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.

DO NOT use with EFAVIRENZ, HIV Inhibitors and OATP1B1/3

DO NOT use with RIBAVIRIN in COMBINATION REGIMENS

  • WARNING: Risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED
  • SIGNIFICANT DRUG INTERACTION POTENTIAL

Screening for NS5A polymorphism is RECOMMENDED when treating patient with HCV genotype 1A.

36
Q

Ribavirin

Ri-Bas-Phere or Rebetol

A

MOA: INHIBIT of REPLICATION of RNA and DNA viruses

INDICATION: HCV in COMBINATION with other agents (DAAs/ INTERFERON ALFA); Toxicity within 4 WEEks

NEVER use as a MONOTHERAPY

Aerosolized form Use for RSV (Respiratory Syncytial Virus); Toxicity in ventilated pt

  • BOX WARNING: Significant TERATOGENIC EFFECTS; not effective as MONOTHERAPY; HEMOLYTIC ANEMIA
  • CONTRAINDICATIONS:

Pregnancy

Women of Childbearing age not on CONTRACEPTIVE

Male Partner of PEGNANT Women

Hemoglobinopathies

CrCl less than 50 mL/min

Autoimmune Hepatitis

DO NOT use with DIDANOSINE

SIDE EFFECTS:

HEMOLYTIC ANEMIA ( especially in Cardiac Disease)

Fatigue, Insomnia, Anorexia, N/V/D, Myalgia, Hypothyroidism, HA

MONITORING: CBC with diff, PLTs, Electrolyte, LFTs/bili, HCV-RNA, TSH, monthly preg test

NOTES: AVOID in PREGNANCY in FEMALE and FEMALE PARTNERS of MALE PATIENTS during therapy DURING THERAPY and 6 MONTHS AFTER COMPLETION.

USE 2 Reliable CONTRACEPTIVE form DURING THERAPY and 6 MONTHS AFTER COMPLETION.

37
Q

INTERFERON ALFA Basic Information

A
  • MOA: Natural produce CYTOKINES that have ANTIVIRAL, ANTIPROLIFERATIVE, and IMMUNOMUDULATORY Effects
  • INDICATION: approved for HBV and HCV
  • PEG-INF-Alfa have POLYETHYLENE GLYCOL added to PROLONG the HALF-LIFE (Wrekly Dosing)

No Longer RECOMMENDED in HCV except if other treatments are CONTRAINDICATED or COSTLY

COMBINATIONS FORMERLY USE :

INF +RBV

INF +RBV + DAA/s

*INTERFERON have TOXICITIES and LAB ABNORMALITIES that limit their use

38
Q

INTERFERON ALFA Basic Information

A

Alfa Treats: HBV, HCV, and Some CANCERS

Beta Treat: MULTIPLE SCLEROSIS (MS)

DO NOT provide a CURE and are HARD to TAKE

FLU-LIKE Syndrome after Injection is Common

39
Q

INTERFERON ALFA DRUGS :

Interferon - Alfa- 2b (Intron A): for HBV and HCV, many CANCERS

Pegylated -Interferon-Alfa- 2b (Pegasys): for HBV and HCV

Pegylated -Interferon-Alfa- 2b (Pegintron, Sylatron): for HCV

A

*SC dosing (Intron x 3; Pegasys and PegIntron x WEEKLY)

*BOX WARNING: can CAUSE or EXACERBATE
Neuropsychiatric, Autoimmune, Ischemic,or Infectious Disorders

If used with RIBAVIRIN,TERATOGENIC/ ANEMIA Risk

CONTRAINDICATIONS: Autoimmune Hepatitis, Decompensated Liver Disease in Cirrhotic patients , Infant/Neonates (Pegasys)

WARNING: Neuropsychiatric, Cardiovascular Events, Endocrine Disorder (hypo/hyper thydroidism/ glycemia), Visual Disorder (Retinopathy, Decreased in Vision), Panncreatis, Myelosuppression, Skin Reaction

*SIDE EFFECTS:

CNS Effect( Fatigue, Depression,Anxiety, Weakness)

GI Upset

INCREASED LFTs( 5-10 x ULN during Treatment)

Myelosupression

Mild Alopecia

*Flu-Like-Syndrome ( Fever, Chills, HA, Malaise); pretreat with APAP and ANTAHISTAMINE

MONITORING: CBC with differential and platelets, LFTs, Uric Acid, SCr, Electrolyte, TGs, Thyroid Function Test, Serum HBV-DNA or HCV-RNA levels

40
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV Basic Information:

A
  • MOA: Inhibit HBV Replication by Inhibiting HBV Polymerase resulting in DNA Chain Termination.
  • APPROVED as MONOTHERAPY for HBV
  • TEST ALL Patients for HIV prior to Starting HBV Therapy
  • Antiviral used for HBV can have activity against HIV and if a pt is CO- INFECTED with BOTH HBV and HIV chose therapy appropriate for both to MINIMIZED RISK of HIV ANTIVIRAL RESISTANCE.
41
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV Basic Information:

A
  • CrCl less than 50 mL/min DECREASED Dose and Frequency (Except VEMLIDY)
  • BOXED WARNING:

Lactic Acidosis

Severe Hepatomegaly with Steatosis (Fatal)

Exacerbation of HBV can occur upon D/C

Can CAUSE HIV Resistance in HBV Patient with Unrecognized or Untreated HIV Infection

42
Q

*NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV

(TDF) Tenofovir Disoproxil Fumarate (Vi-Read)

(TAF) Tenofovir Alafenamide ( Ve-Mil-Dy)

A
  • VIREAD and VEMILDY
  • VEMILDY not RECOMMENDED in CrCl less than 15 mL/min
  • WARNING:

Renal Toxicity including acute renal failure

Faconi Syndrome

Osteomalacia

DECREASED Bone Density

*SIDE EFFECT:

TDF: *Renal Impairment, *Decreased Bone Mineral Density, N/V/D, HA, Depression, Increased LFTs and CPK

TAF: *Nausea, Decreased Bone Mineral Density, Abdominal Pain, Fatigue, Cough, HA, Increased LFTs

NOTES:

  • VIREAD ( TAF) and VEMILDY (TDF): Protect from moisture; DISPENSE only in ORORIGINAL CONTAINER
  • TAF is associated with Decrease RENAL and BONE TOXICITY Compared to TDF

VEMILDY (TDF) Approved only for HBV

43
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV

Entecavir ( Bara-Clude)

A
  • BARACLUDE
  • Take on Empty Stomach

SIDE EFFECTS:

Peripheral Edema

Pyrexia

Ascites

Increase LFTs

Hematuria

Nephrotoxicity

Increase SCr

NOTES:

Food reduce AUC by 18 to 20% ; take on an empty stomach 2hrs before or after a meal

44
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV

Adefovir (Hep-Sera)

A
  • HEPSERA
  • BOXED WARNING:

Caution in patients with RENAL IMPAIRMENT or those at RISK of RENAL TOXICITY ( including concurrent NEPHROTOXIC agents or NSAIDs)

SIDE EFFECTS:
HA, Weakness, Abdominal Pain, Hematuria, Rash, Nephrotoxicity

45
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV

Lamivudine ( Epi-Vir HBV)

A

*BOXED WARNING:

DO NOT used Epivir for Treatment of HIV ( Contains lower dose of Lamviduvine) can result in HIV Resistance.

SIDE EFFECTS:
*HA, N/V/D, Fatigue, Insomnia, Myalgias, Increase LFTs

46
Q

NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV

Lamivudine ( Epi-Vir HBV)

A

*BOXED WARNING:

DO NOT used Epivir for Treatment of HIV ( Contains lower dose of Lamviduvine) can result in HIV Resistance.

SIDE EFFECTS:
*HA, N/V/D, Fatigue, Insomnia, Myalgias, Increase LFTs

47
Q

NRTI Counseling

A

Epivir HBV Tabs and Oral Solutions are not INTERCHANGEABLE with Epivir( higer dose)

48
Q

What is CIRRHOSIS and it’s COMMON CAUSE?

A

Advanced FIBROSIS Scarring) of the liver that is usually IRREVERSIBLE.

COMMON CAUSE:

Hepatitis C

Alcohol Consumption

49
Q

In CIRRHOSIS, as scar tissue replaces the healthy liver tissue blood flow through the liver is impaired cause complications.

What ate these COMPLICATIONS ?

A

Portal Hypertension

Varices

Ascites

Hepatic Encephalopathy

50
Q

What are the SYMPTOMS of CIRRHOSIS?

A

*Yellow skin and yellow white of the eyes (JAUNDICE)

N/V/D

Loss of Appetite

Malaise

Pain in upper right quadrant of abdomen

Darkened Urine and/or lightened color (white or clay-colored) due to low bile production

51
Q

LAB TESTS for LIVER disease: what is

Aspartate Aminotransferase (AST)

Alanine Aminotransferase (ALT)

A

AST and ALT are LIVER Enzymes

Normal Range for BOTH : 10-40 units/L (vary)

HIGHER Values= MORE ACTIVE (acute) the LIVER Disease

52
Q

What is the CLINICAL SIGNS of LIVER Disease?

A 
*INCREASE:
 ALT
 AST
ALP or Alk Phos ( Alkaline Phosphate)
Tbili ( Total Bilirubin)
LDH ( Lactate Dehydrogenase)
PT ( Prothrombin Time)

*DECREASE:
Albumin ( PROTEIN produced by the liver; normal range 3.5 - 5.5 g/dL)

Note: Albumin and PT/INR are markers of synthetic ( PRODUCTION ABILITY) liver function and likely alter in chronic liver disease ( cirrhosis).

53
Q

LIVER Disease can be CLASSIFIED as:

A

Hepatocellular ( Increase ALT and AST)

Cholestatic (Increase Alk Phos and Tbili)

Mixed (Increase ALT, AST, Alk Phos and Tbili)

54
Q

Lab ABNORMALITIES to distinguished between TYPES of LIVER Disease:

A
  • Acute Liver Toxicity (Drugs):
  • Increase ALT/AST

*Chronic Liver Disease (Cirrhosis):
-Increase ALT/AST, Alk Phos, Tbili
LDH ,PT/INR
-Decrease Albumin

*Alcoholic Liver Disease:
-Increase AST greater than increase ALT
( AST will be about double the ALT)
- Increase GGT (Gamma-Glutamyl Transpeptidase)

  • Hepatic Encephalopathy:
  • Increase Ammonia
54
Q

Lab ABNORMALITIES to distinguished between TYPES of LIVER Disease:

A

*Acute Liver Toxicity ( Including Drugs)

55
Q

Assessing severity of LIVER Disease:

Child-Turcotte- Pugh (CPT) or

Child Pugh Classification System
( Online Calculatoion System)

Model End-Stage Liver Disease (MELD)

A

CPT Score Range: 0 to 15

Class A (Mild Disease): < 7

Class B (Moderate Disease) : 7 - 9

Class C (Severe Disease): 10 - 15

MELD another scoring system ranges from 0-40; HIGHER number = GREATER RISK of death within 3 MONTHs.

56
Q

Information to GUIDE Hepatically Cleared Agent in LIVER FAILURES

A

Information NOT widely AVAILABLE.

In PACKAGE INSERT, caution is ADVISED when using hepatically cleared agent in SEVERE LIVER DISEASE

Generally is best to START at LOWER DOSE and TITRATE

57
Q

NATURAL Products and LIVER Disease

A
  • Milk Thistle : use by patients with liver disease, not harmful but limited data on efficacy.
  • SE of Milk thistle: Diarrhea

Drug INTERACTION : Milk thistle and Antiviral HCV Meds

Kava, Comfrey and Flavocoxid (Limbrel) are known Hepatotoxins.

58
Q

SELECTED Key DRUGs that has BOXED WARNING for Liver Damage.

A

Acetaminophen ( High Doses, Acute or Chronic)

Isoniazid

Ketoconazole

Methotrexate

Nefazodone

Nevirapine

NTRIs

Propylthiouracil

Tipranavir

Valproic Acid

59
Q

Other DRUGs that has BOXED WARNING for Liver Damage.

A

Amiodarone

Bosentan

Felbamate

Flutamide

Leflunomide and Teriflunomide

Lomitapide

Maravirioc

Mipomersen

Tolcapone

60
Q

Drug Induced Liver Injury:

Many Drugs can cause Liver Damage

A

Primary Treament : STOP DRUG

DISCONTINUE: when LFT are > 3 times the UPPER LIMIT of NORMAL ( > 150 units/L of ALT or AST)

Agent can be rechallenge if clinically necessary.

DILI( Drug Induced Liver Injury) website:
http://livertox.nih.gov

61
Q

What KNOWN Hepatoxic Agent can cause SEVERE INJURY?

A

Acetaminophen (APAP); can be use at low dose for limited period in Cirrhosis pt

NSAIDS should be AVOIDED in patients with CIRRHOSIS due to Deocompensation and Bleeding

ACTIVE ALCOHOLIC = Futher Liver Damage

62
Q

ALCOHOL Induce Liver Disease

A

Most Common DILI ( Drug Induced Liver Disease)

Includes: Fatty Live, Alcoholic Hepatitis, and Chronic Hepatitis with hepatic fibrosis or cirrhosis.

Chronic Alcohol ingestion over long period of time can causes STEATOSIS or Fatty liver.

Risk increase with drink amounts; WOMEN more than MEN

63
Q

ALCOHOL Induce Liver Disease PATHOPHYSIOLOGY

A

Chronic alcohol consumption result in secretion of pro Inflammatory (TNF-alpha, IL-6, and IL-8) cytokines, stress and toxic these factors causes inflammation, apoptosis and eventually fibrosis of liver cell.

64
Q

ALCOHOL Induce Liver Disease TREATMENT

A

*ALCOHOL CESSATION

DRUGS:

*Benzodiazepines: WITHDRAWAL in INPATIENT

Anticonvulsants: WITHDRAWAL in OUTPATIENT

*Naltrexone (Revia) , Acamprosate (Campral), and Disulfiram( Antabuse): use to PREVENT RELAPSES

Vitamins and Trace mineral ; Vit A,D, thiamine(Vit B1), folate, pyridoxine (Vit B6)
and Zinc to help REVERSE MALNUTRITION

  • THIAMINE is use to PREVENT and TREAT Wernicke-Korsakoff Syndrome ( BRAIN DAMAGE cause by LACK of VITAMIN B1)
  • Supportive Group

Avoid Hepatotoxic Drugs

65
Q

Complications of Liver Disease and Cirrhosis:

PORTAL HYPERTENSION

VARICEAL BLEEDING

A

PORTAL HYPERTENSION: Increase BLOOD PRESSURE in the PORTAL VEIN

This cause COMPLICATIONS including development and BLEEDING of ESOPHAGEAL VARICES (englarged veins in the lower part of the esophagus)

VARICEAL BLEEDING (FATAL) : cause by BLOCKAGE of blood flow through the Liver by scar tissue , it backs up and flow into smaller vessels causing a balloon effect and bleed of break open.

66
Q

VARICEAL BLEEDING TREAMENT

A

FIRST LINE TREATMENT:

Band Ligation: putting a BAND AROUND the VESSEL

Sclerotherapy: INJECTING a SOLUTION into the VESSEL to make it COLLAPSE and CLOSE

Note: Band Ligation and Sclerotherapy are procedures performed by a physician using endoacopy.

SUPPORTIVE THERAPY: Blood Volume Resuscitation/ Blood Product, Mechanical Ventilation, Correction of Coagulapathy, Attempts to Stop Bleeding and Prevent Rebleeding

DRUGs:

  • Ocreotide (Sandostatin): Selective
  • Vasopressin (Vasostrict): Non-Selective

SURGICAL PROCEDURE:

Ballon Tamponade

Tranajugular Intrahepatic Portosystemic Shunt (TIPS)

NOTE: Consider surgery if patients is not responding to treatment and for future prevention

SECONDARY PREVENTION:
Non-Selective Beta Blocker( Nadolol and Propranolol) after resolution and Endoscopic Variceal Ligation

67
Q

Complications of Liver Disease and Cirrhosis:

PORTAL HYPERTENSION TREAMENT

A

BETA Blocker REDUCE portal pressure by reducing portal venous in flow via 2 mechanism::

  1. DECREASE Cardiac Output( Via BETA-2 blockade)
  2. DECREASE Splanchnic Blood Flow by Vasoconstriction (Via BETA-2 blockade and unopposed Alpha Activity)

Titrated to MAXIMAL tolerated dose (Target HR 55 - 60 BPM)

68
Q

Complications of Liver Disease and Cirrhosis:

Medications that VASOCONTRICT the SPLANCHNIC (GI) Circulation to stop and minimize the bleeding.

Octreo-Tide (San-Do-Statin)

Vaso-pressin (Vasostrict)

A

*Octreo-Tide (San-Do-Statin): Analog of Somatostatin with greater potency and longer duration of action

SIDE EFFECTS: *Bradycardia, *Cholelithiasis, *Biliary Sludge, Chest Pain, Fatigue, HA, Pruritus, Constipation, NVD, Myalgias, Hyper/Hypoglycemia, URTIs, Arthropathy, Abdominal Pain, Malaise, Fever, Hypothyroidism

MONITORING:BG, HR, ECG

*Vaso-pressin (Vasostrict): Antidiuretic Hormone Analog; use with NITROGLYCERIN to PREVENT MYOCARDIAL ISCHEMIA

SIDE EFFECTS: Arrhythmias, Chest Pain, MI, Decreased Cardiac Output, Increase BP, N/V

MONITORING: BP, HR, ECG, Fluid Balance

69
Q

Non-Selective Beta-Blockers USED in PORTAL HYPERTENSION and VARICEAL BLEEDING

A

*Nadolol (Corgard)

Propanolol (Inderal)

BOXED WARNING:
Do Not WITHDRAW ABRUPTLY taper gradually to Avoid acute Tachy, HTN, Ischemia

CONTRAINDICATIONS:
Sinus Bradycardia
Asthma Exacerbate

WARNING:
Use for PORTAL HYPERTENSION

Extreme CAUTION in Asthma and COPD, Peripheral Vascular Disease, Raynaud’s Disease, DIABETES, PSYCH

MONITOR:
HR and BP

70
Q

Complications of Liver Disease and Cirrhosis:

Hepatic Encephalopathy (HF)

A

Caused by ACUTE or CHRONIC Hepatic Insufficiency

SYMPTOMS: *Due to Accumulation of Gut-derived Nitrogenous Substance in the Blood ( Ammonia, Glutamate)
*Musty Odor of the Breath and/or Urine,
* Changes in thinking,
*Confusion,
*Forgetfulness,
*Hand Tremor (Asterixis) ,
Mood Changes, Poor Concentration, Drowsiness, Disorientation, Worsening Handwriting, Sluggish Movements, and Risk of Coma.

*Daily PROTEIN intake: 1-1.5g/Kg Vegetables and Diary Protein PREFFERED due to lower calories yto Nitrogen Ratio.

71
Q

TREATMENT of Hepatic Encephalopathy (HF)

A

Goal: Identifying and treating precipitating factors and REDUCING Blood AMMONIA levels through diet (LIMIT ANIMAL PROTEIN) abd drug therapy

DRUGs:
NON-ABSORBALABLE DISSACHARIDES (FIRST LINE):
Lactulose ( Enulose, Constulose, Kristalose)

ANTIBIOTICS:
Rifaximin ( Xifaxan): (SECOND LINE)

Neomycin

Metronidazole (Flagyl, Metro)

72
Q

TREATMENT of Hepatic Encephalopathy (HF) DRUGs:

NON-ABSORBALABLE DISSACHARIDES (FIRST LINE TREATMENT):

Lactulose ( Enulose, Constulose, Kristalose)

A

Lactulose (* Enulose, Constulose, Kristalose)

MOA: *Convert AMMONIA to AMMONIUM( polar cannot diffuse into the blood); ALSO diffuse Ammonia into colon for excretion

SIDE EFFECTS:
*Flatulence
*Diarrhea
*Dyspepsia
*Abdominal Discomfort
Dehydration, Hypernatremia, and Hypokalemia

MONITOR: Mental Status, Bowel Movements, Ammonia, Fluid Status, Electrolyte

73
Q

TREATMENT of Hepatic Encephalopathy (HF) Drugs:

ANTIBIOTICs:
Rifaximin ( Xifaxan): (SECOND LINE)
Neomycin
Metronidazole (Flagyl, Metro)

A

MOA: INHIBIT the activity of UREASE-Producing BACTERIA, decreasing the AMMONIA Production

DRUGS:
RIFAXIMIN( Xifaxan): (SECOND LINE)

SE: Peripheral Edema, Dizziness, Fatigue, Fatigue, HA, Nausea, Ascites

MONITORING:Mental Status, Ammonia

NEOMYCIN
SE: *GI Upset, Ototoxicity, Nephrotoxicity, Irritation/Soreness of Mouth/rectal area

MONITORING: Mental Status, Ammonia, Renal Function and Hearing

BOXED WARNING:* Neurotoxicity, Nephrotoxicity, Neuromuscular Blockade and Respiratory Paralysis

METRONIDAZOLE (Flagyl, Metro)

WARNING: DO NOT used LONGTERM due to PERIPHERAL NEUROPATHIES

74
Q

Complications of Liver Disease and Cirrhosis:

Ascites

A

FLUID ACCUMULATION within the PERITONEAL SPACE that can lead to SBP and HRS

*Spontaneous Bacteria Peritonitis (SBP) : ACUTE Infection of the ASCITIC FLUID

TREATMENT: Targets Streptococci and Enteric Gram Negative Pathogens

CEFTRIAXONE

*Hepatorenal Syndrome (HRS): RENAL FAILURE in patients with ADVANCED CIRRHOSIS.

CAUSE: renal constriction mediated by activation of RAAS and SNS through HEPATORENAL reflex feedback mechanism.

PREVENTION: Treat CIRRHOSIS; AVOID Nephrotoxin and Renal Hyperfusion

DRUGS: Albumin, Octreo-Tide, Midodrine

75
Q

ASCITES TREATMENT S

A

Portal Hypertension:* RESTRICT Dietary Sodium intake to < 2g/day; AVOID sodium retaining drugs (NSAIDS) ; DIURETIC to increase fluid loss Except in SEVERE HYPONATREMIA(Na <120 mEq/L).

DRUGs for ASCITES: Diuretics:

Monotherapy: Spironolactone

Combination: Spironolactone + Furosemide (not effective alone)

Spironolactone ( initiate at 50-100 then 400/d)

Furosemide ( Ratio: 40mg to 100mg Spironolactone to maintain K balance)

*ALL PATIENTS with Cirrhosis and Ascites: should consider LIVER TRANSPLANT

LIVER (1 decks)

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