Liver Flashcards
Where is the liver located?
Right upper quadrant of the abdomen
What are the lobules of the liver?
connected by small ducts and centered on a branch of the hepatic vein
Portal Triads at the corner of adjacent lobules
What is the hepatic duct?
Transports bile produced by the liver cells to the gallbladder and duedenum
Liver cells can generate at what %?
About 70% of thel iver tissue can be destroyed before the body is unable to eliminate drugs and toxins via the liver
What is average blood flow to the liver?
25% of cardiac output so 1500mL of blood/flow/minute
Where does venous flow from the portal vein do?
Venous blood from the SMALL intesitne which absorbs nutrients, drugs, toxins and is direct to the liver
Pancreatic venous drainage
Spleen
Arterial flow in the from the hepatic artery does what?
Liver oxygenation
Venous flow out through teh hepatic vein
BLood from both the portal vien and hepatic artery mixes together in the sunisoids and exits the liver through the hepatic vein.
What is excreted the from tliver?
Bile
What under goes metabolism in the liver?
Billirubin, drugs, nutrients, hormones,
What is storred in the liver?
Vitamins/minerals (b12, Iron) CHO
what is synthesizedin the iver?
Plasma proteins such as albumin coagulation proteins and other tranpsort proteins
What is the purpose of the gallbladder?
Stores and concentrates bile
What is the function of Bile?.
Emulsification of Dietary fat, chol, vitamins
Elimination of waste excess chol, xenobioitcs and bilirubin
What is the end product of heme degreadation
Breakdown of RBC in spleen/liver
Insoluble (Bound t o albumin for transport to liver
What is bilirubin metbabolism?
Glucuronidated in liver
Excreted in bile
What are the general patterns of hepatocellular injury?
What are the etiological causes of hepatic injury?
Viruses
Drugs
Environmental toxins
Alcohol
What is cholestasis?
A failure of normal amounts of bile to reach the duodenum
Leads to accumulation of bile in liver cells and biliary passages
What causes Cholestasis?
– Cholelithiasis (gall stones) - most common
– Tumor, viral hepatitis, alcohol-related liver disease, drugs
– Primary biliary cholangitis (PBC), primary sclerosing
cholangitis (PSC)
What can cause Primary biliary cholangitis?
- Caused by the slow, immune-mediated destruction of
small bile ducts within the liver - Leading cause of liver transplant in women in Canada
What is primary sclerosing cholangitis?
- Involves progressive inflammation and fibrosis affecting
any part of the biliary tree
What does PSC lead to?
- Leads to the progressive destruction of bile ducts
What is PSC commonly associated with?
- Commonly associated with inflammatory bowel disease
What is cholestatic syndrome? Signs/Symptoms?
- Pruritis
- Jaundice
- Dark Urine
- Light coloured stools
- Steatorrhea
- Xanthoma and xanthelasma
- Hepatomegaly
- Features specific to disease
What is URSO?
Naturally occurring bile acid
What is the MOA of URSO?
decrease chol saturation
What is URSO used for?
– Gradual dissolution of stones in 30-40%
– Stones often recur after drug d/c
What is OCA Obeticholic acid
Alternative for PBC
What is URSO used for in tersm of chronic forms of cholestasis?
such as PBC or PSC
– Improves serum biochemical tests
– Limited efficacy in preventing disease progression in PSC
What are the drug treatments for Pruritis?
Cholestyramine *Most efficacious)
Antihistamines
Naltrexone
Rifampin sertraline
What are the causes of hepatocellular damage?
– Toxic agents: Alcohol, drugs, toxins
– Infections: Hepatitis
– Longstanding cholestasis
– Ischemic injury: Thrombosis
– Other Diseases (autoimmune, iron overload)
What does Hepatocellular damage depend on?
– Duration of assault (cells can regenerate)
– Intensity of assault (massive: fulminant hepatic failure vs
mild to moderate: hepatitis)
– Tremendous reserve capacity of liver
What happens when hepatoctes are destroyed?
– contents of cells are released into the circulation
– functional ability of the liver may be compromised (if
enough damage has occurred)
What liver enzyme measurements are released into circulation post injury?
– ALP, AST, ALT, GGT
What do the ALP, AST, ALT, GGT help us do?
– Helps to distinguish type of injury.
– Cholestatic
– Hepatocellular
– Other
What is the ALP test?
ALP (Alkaline phosphatase)
– Present in bile duct > hepatocytes
– High concentrations also found in bone
What is the GGT test?
GGT (Gamma glutamyl transpeptidase)
– All liver disorders
– Confirms hepatic origin of ALP
– Also: EtOH, pancreatitis, MI, COPD, renal
What is AST/ALT test?
Aminotransferases (AST, ALT)
– (aspartate aminotransferase, alanine
aminotransferase)
– ALT more specific than AST
– Poor correlation with severity, prognosis
– May be minimally elevated in cholestatic syndromes
What are the ABC tests for testing the synthetic capability of the liver?
Albumin, Bile, Clotting
What is the albumin level correlate/general information/
– Normal lifespan ~20 days
– Reduced after sustained assault
– Sx: edema, ascites
– Effects on calcium, highly bound drugs (phenytoin).
– Pre-albumin level
What is the bilirubin test?
Results of bilirubin retention leads to deposits in skin and tissues causing dark urine, pale stools, yellow skin
What causes Increased levels of bilirubin?
– Obstruction: Cholestasis
– Impaired metabolism: Hepatocellular
– Excessive production: e.g…….?
Unconjugated bilirubin is?
Bound to albumin, not soluble in water and measured as indirect
Conjugated Bilirubinemia is?
Conjugated by the liver, soluble in water, measured as direct
What is the clotthing prothrombin time?
Since the Liver synthesized coagulation factors (I, II, V, VII, IX, and X)
During states of liver damage we will this will lead to INR increases. 70% of liver capacity needs to be loss in order to see this change too.
Which Coagulation factor can be measured if we want to rule out Vitamin K deficiency?
Factor V
Generally what does AST correlate to?
RBC, Muscle, Liver
What does ALT correlate to?
Liver
What does ALP correlate to?
Liver Bone Placenta
What does GGT correlate to?
Liver*** This is very liver specific
Review the slide next
During hepatocellular and cholestatic describe the increases in ALP
During hepatocellular and cholestatic describe the increases in GGT
During hepatocellular and cholestatic describe the increases in AST
During hepatocellular and cholestatic describe the increases in ALT
During hepatocellular and cholestatic describe the increases in LDH
What is Cirrhosis?
A chronic diffuse disease characterized by fibrosis and
nodular formation
What does Cirrhosis result from?
continuous liver injury
– Ex: repeated acute liver injury in alcohol use disorder
– Takes a long time to develop
What happens to the liver in cirrhosis?
liver becomes hard, shrunken, and nodular
– Loss of normal structure and function
– Irreversible fibrosis (scarring)
What are the causes of liver cirrhosis?
Causes: alcohol, viral,
autoimmune, inherited,
drugs/toxins, Non-alcoholic fatty
liver disease, etc
What is non-alcoholic fatty liver disease?
Fatty liver disease that looks like it was alcohol induced
What is Non-alcoholic steatohepatitis
A disease that looks like alcohol disease but not caused by it. Instead more so related to insulin resistance.
Just more fatty liver then actual fatty liver
How much alcohol is required to cause liver cirrhosis?
women more susceptible then men, but once >5 drinks per day both men and women are at increased risk substantially
WHat is the diagnosing criteria for cirrhosis?
Biochemical markers
Fib-4 score
AST to platelet ratio index
Abdominal aultrasound
Elastrography
Liver biopsy
what are biochemical markers used for?
Screening
What is the Fib-4 score used for>
helps to estimate the amount of scarring in the liver/risk of
fibrosis using age, platelet count, AST and ALT
What is the AST to platelet ratio index used for>
Used to estimate liver fibrosis specifically in patients with
hepatitis C
What is the abdominal ultrasound used for?
generally the first imaging modality recommended when liver
disease is suspected
What is elastropgraphy?
Relatively new, non-invasive way to determine liver stiffness
– Measures propagation speed of mechanical waves through
liver parenchyma
WHat is the stage 2-3 fibrosis of a elastography indicate?
Stiffness = 7-11kPa
What is stage 4 fibrosis?
Cirrohiss >11-14kPa
What are the limitations of elastrography?
low reliability in patients with obesity, ascites and
artificially elevated stiffness due to severe liver inflammation or
steatosis
What is a liver biopsy and its role?
Rarely needed now for diagnosis
Still has a role in definitive diagnosis of underlying cause
what does liver cirrhosis result form?
Decreased funcitoning liver tissues and impaired function and diminished reserve
Portal hypertension too!
What is the prognosis of liver cirrhosis?
Patients will die in 5-15 years after dx of cirrhosis?
What is the treatment of liver cirrhosis?
– Of the specific disease
– Of the complications (bleeding esophageal varices, ascites,
encephalopathy)
– Liver transplantation
What is compensated Liver Cirrhosis?
Body may continue to function well/normal
What is decompensated liver cirrhosis?
– severe scarring & disruption of function
What are the symptoms of compensated liver cirrhosis?
Asymptomatic
Non-specific symptoms inclusive of: * Anorexia, weight loss, weakness, NV, GI upset, muscle
wasting
* LETs may be abnormal
What are the symptoms of decompensated liver cirrhosis?
confusion, edema, fatigue, bleeding
What are the abnormal lab functions of decompensated?
INR, albumin, bilirubin
What else may occur due to decompensated liver cirrhosis?
- Signs of chronic liver disease
- Portal HTN, ascites, varices, encephalopathy
What are the potential labratory presentations of cirrhosis?
– Hypoalbuminemia
– Elevated prothrombin time (PT)
– Thrombocytopenia
– Elevated alkaline phosphatase (ALP)
– Elevated aspartate transaminase (AST), alanine
transaminase (ALT), and γ-glutamyl transpeptidase
(GGT)
– Elevated bilirubin
What is the portal system?
Normally self-contained, low-pressure venous system
What is portal HTN
Results from increase in resistance to portal flow and
increase in portal venous inflow
What is splanchnic dilation related to?
Portal htn
What does RAAS do during Portal HTN?
Activate
What is the vicious cycle of portal hypertension?
End up with “back flow” of blood and widening of the
venous channels that connect the portal and
systemic circulation
What is splenomegaly?
Spleen enlarges 3-6x
– May be uncomfortable/painful to patient
What causes splenomegaly?
↑ sequestering and destruction of RBCs
– anemia
– thrombocytopenia
What are the 4 consequences of portal to systemic shunting?
– metabolites/toxins in the blood have not been processed
by the liver first
– ↑ sensitivity to noxious substances absorbed from the GI
tract (encephalopathy)
– malabsorption of fat in the stool (↓ bile flow)
– Contributes to all other complications as well: ascites,
SBP, varices, hepatorenal sx
What are noxious substances?
pollutants
Waht is ascites?
Collection of fluid in the peritoneal cavity
– Many liters may collect (up to 20L +)
– Can cause massive distension
What is the pathogenesis of asictes?
– Hydrostatic pressure
– Hypoalbuminemia (reduced oncotic pressure)
* Causes relative hypovolemia→aldosterone secretion in response
– Renal retention of Na+ and water
What is SAAG
serum-ascites albumin gradient
What does it mean if someones SAAG value is >11g/L?
indicates portal hypertension
- Likely responsive to diuresis
What if someones SAAG value is <11g/L?
likely other causes (e.g. infection, malignancy
* Not typically responsive to diureses
If you have a total protein concentration of >25g/L and SAAG >11 what does this suggest?
Cardiac dysfunction as the etiology of ascites
What is the goal of ascites management?
Remove abdominal fluid and prevent sx ant maintain reasonable QOL
What are the management strategies of ascites?
– Salt restriction
– Diureses
– Paracentesis
– TIPS
– Liver Transplant
What is the generally flow of management of ascites?
What is TIPS?
Transjugular intrahepatic portosystemic shunt
Helps blood bypass diseased liver
What are the two medications used for diureses?
Spironolactone and furosemide
What is paracentesis?
– Aspiration of peritoneal fluid with a needle
– Large volume aspiration may result in “fluid steal” from
the vascular space
– Paracentesis + Albumin may be helpful
– May help ↓ discomfort
– Risk of abdominal perforation and infection
What should be monitored with spironolactone therapy?
Hyperkalemia
Dehyrdation
Estrogen like side effects
What are the drug interactions of spironolactone?
Digoxin levels may increase because of the excess in K
What may occur when on Furosemide and Spironolactone therapy?
Hypovolemia
What is the general dosing for spironolactone and furosemide?
100mg and 40mg po od
What are the highest values that we can go up with spironolactone and furosemide?
400mg and 160mg
What diuretic can be added with spironolactone and furosemide?
Metolazone
Which drug may sub spironolactone?
Amiloride
What should be monitored when on Spironolactone and furosemide?
SCr, Na, K, weight, BP
What is refractory ascites?
Unresponsive to sodium-restricted diet and high-dose
diuretic treatment
- (400 mg/day of spironolactone and 160 mg/day of furosemide)
Essentially occurs rapidly after occuring
What is the treatment of Refractory Ascites?
– serial therapeutic paracentesis, (+/- albumin)
– transjugular intrahepatic portasystemic shunt (TIPS),
– or liver transplantation
What is the goal of Ascites?
Gradual weight loss
Monitor creatinine serum Na and K frequently, Consider SBP
What is Spontaneous bacterial peritonitis?
- Infection in ascitic fluid without obvious cause
- Thought to be from bacteria translocation (the passage of bacteria
from the gut to the bloodstream and other extraintestinal sites,
together with decreased host defenses
What are the symptoms of Spontaneous bacterial peritonitis?
Fever, chills, abd pain, etc…
What are the general mortality rates of SBP?
Very high so when individuals present to emerge with ascites they should be evaluated and tests should be performed
When should we treat spontaneous bacterial peritonitis?
Empirically treat:
– Culture positive
– PMN >250/uL OR a high degree of suspicion for SBP (do not wait
for culture if you don’t have one)
Hence, TREAT ASAP
What is the common treatment for community acquired SBP?
Cefotaxime of ceftriaxone for 5 days
What si the common treatment for hospital acquired SBP?
Piperacillin/tazobactam
Meropenem+- Vanvomycin
What are the clinical signs that infection has decreased?
PMN count decreased by 25% (polymorphonuclear leukocyte)
Who should be considered for SBP prophylaxis?
pts having survived an episode of
SBP (secondary prophylaxis), or those at high risk (primary
prophylaxis)
What is considered high risk for SBP prophylaxis?
low ascitic fluid total protein ascites or variceal
hemorrhage
What is hepatorenal syndrome?
Renal failure in patients with severe liver disease
How is Hepatorenal syndrome categorized?
Severe vasoconstriction of the renal
circulation
What is the treatment of Hepatorenal syndrome?
Stop diuretics and avoid all potential nephrotoxins such as NSAIDS and aminoglycosides
What is Varcies?
High pressure in portal vein
– Creates “bypasses” or shunts (collaterals)
Relatively small veins become engorged with an
excess of blood
What are the principle sites of varices?
– Veins in rectal area (hemorrhoids)
– Abdominal wall (umbilicus)
– Esophageal varices
How common are esophageal varices?
65% of patients with advanced cirrhosis
What is the issue with esophageal varices?
High risk of recurrent hemorrhage and possible require prophylaxis
What is the medical treatment for Variceal bleed?
– Adequate blood volume resuscitation
– Protection of airway from aspiration of blood
– Prophylaxis against SBP and other infections
– Control of bleeding
– Prevention of re-bleeding
– Preservation of liver
function/prevention of hepatic
encephalopathy
– Prevention of acute kidney injury
What are the treatment strategies of variceal bleeding?
Packed red blood cells to help resuscitate blood volume
Abx prophylaxis for SBP
Octreotide or somatostatin (Vasoconstrictors)
What is the prevention of variceal bleeding?
Propranolol and nadolol,, which are used. They are non-selective
What is the dosing regimen of Nadolol and propranolol?
What is the othern on-pharmacological prevention of varcieal bleeding?
Endoscopic variceal ligation
What isthe secondary prophylaxis of Variceal bleeding prevention?
– Non-selective beta blocker + EVL
– TIPS for those who have re-bleeding despite therapy
What is hepatic encephalopathy?
CNS dysfunction observed in late-stage cirrhosis
What causes hepatic encephalopathy?
– Accumulation in the bloodstream of neurotoxic
substances that are normally removed by the liver
– MOA not entirely clear but a number of substances
have been implicated
* Ammonia
* Tryptophan
* GABA’ergic compounds
What is the presentation of Encephalopathy?
Presentation variable
– Drowsiness, personality changes, confusion, motor sx’s
– Many sx are reversible with appropriate therapy
– Severity of sx is “graded”
What is the txt of Encephalopathy?
Lactulose
What are alternative therapies to Lactulose?
Metronidazole
Rifaximin
Patients with cirrhosis often lack which vitamins?
ADEK (Fat soluble
What vitamins need to supplemented due to nutrient deficiencies associated with heavy alcohol use?
B1, B6, and Folate
What is asymptomatic Hepatitis generally associated with?
Elevated AST and ALT levels
What is acute hepatitis symptoms?
flu-like symptoms, abdominal pain, jaundice, scleral
icterus, pale stools, dark urine
What is acute fulminant hepatitis?
Rare but may be fatal
What is chronic persistent hepatitis
Delayed recovery with minimal liver damage but failure to develop antibody
What is chronic active hepatitis?
Progressive liver damage, failure to develop antibody, may be asymptomatic
What is Hep A/
RNA virus that can be transmitted via fecal-oral route,
More likely to occur in travel to countries with higher rates or poor conditions and hygine
Is Hep A vaccine?
Yes! havrix, Acaxim, Vaqta
What is the general symptomalgy of Hep A?
Fever, jaundice, scleral icterus
Hepatomegaly upon physical examination
How long do Hep A symptoms generally last?
3 months
Is Sequelae of Hep a common?
No Fulminant hepatitis is rare
Mortality of Hep A?
Low
Is Hep A chronic?
No
What is the treatment of HepA?
Supportive therapy, avoiding hepatotoxic drugs and Etoh
No clear pharm therapy
What can be done to prevent hep a?
Vaccines
What can be given post-exposure for prophylaxis?
Hep A vaccine 14 days within 14 days of exposure,
Immunoglobulin if patient is under 1 or vaccine unabailable
What are the serological markers of Hep A?
Total anti-HAV
anti-HAV IgG
anti-HAV IgM
What does Total anti-HAV mean?
Total IgG and IgM antibodies to HAV
May indicate acute, resolved infection or immunity
What does anti-HAV IgG represent?
Immunity from vaccine or previous exposure (Life long protection)
What does anti HAV IgM indicate?
Acute HAV infection
What is HepB?
DNA virus that is transmitted either perinatal, sexual, or blood
What is the prevention of HepB?
Vaccibes!
What are the symptoms of HepB?
Young people will generally be asymptomatic, but older patients will be jaundice, dark urine, white stool, abdominal
pain, fatigue, fever, chills, loss of appetite, and pruritus possibly.
Mostly asymptomatic
What are the serological markers of HepB? (All)
HBsAg
Anti-HBs
Anti-HBc total
Anti-HBc IgM
HBeAg
anti-HBe
HBV-DNA
What are the three serological markers we should know for HepB?
HBsAg
Anti-HBs
HBV-DNA
What is HBsAg?
Indicated HBV infection, acute or chronic
What is Anti-HBs
marker of HBV
immunity; in cases where both HBsAg and anti-HBs are present, HBV
infection persists
What is HBV-DNA?
a marker of viral replication/infectivity detectable at the
start of acute infection and used to assess and monitor the
treatment of chronic HBV infection
When is screening recommended for HBV?
Once atleast when you are over 18
High risk groups
What is the treatment of HBV?
Interferon or Nucleoside analogues
What is the treatment goal of HepB treatment?
Permanent suppression/elimination of the virus and prevent cirrhosis, liver failure and hepatocellular carcinoma
What is duration of therapy for IFN treatment of HepB?
16-48wk course, 30% successful in developing immunity
What are the pros/cons of IFN treatment?
- Shorter course of therapy
- Absence of resistance
- A chance at full seroconversion
What are the cons of IFN treatment?
– Contraindicated in decompensated cirrhosis
* Increased risk of life-threatening infections and
possible worsening of hepatic decompensation
– Subcutaneous injection
– Many side effects!
* Influenza-like illness, emotional lability,
myleosuppressive effects, hyper/hypothyroidism
What are the treatment outcomes of nuceloside analogues?
- > 90% response, 10-15% success in developing immunity
(40-50% seroconversion in 5 years, varies with agent)
What are the advantages of nucleoside analogues?
– Safer
– fewer side-effects
– Po
What are the disadvantages of Nuceloside analgoues?
– chronic therapy –
* endpoint is seroconversion + 12 months(durability
75%)
* This can take years and some may require
treatment indefinitely
– drug resistance
Renal dysfunction dose adjustment
What are the nucleoside analogues used for HepB treatment?
Lamivudine
Adefovir
Tenofovir
Entecavir
What is LAMIVUDINE MOA?
Pyrimidine nucleoside analogue inhibitor of HBV
What is LAMIVUDINE generaly used for?
Prophylaxis
What is LAMIVUDINE issue now a days?
Resistance
What is Adefovir MOA?
Nucleotide analogue
How is Adefovir used?
– Less potent & does not achieve viral suppression in most in
the first year (likely from low approved daily dose)
– Useful add on in lamivudine resistance
What are the side effects of Adefovir?
Nephrotoxicity, hypophosphatemia
What is Tenofovir MOA?
Theres 2 forms
▪ Tenofovir disoproxil fumarate (VIREAD )(TDF)
▪ Tenofovir alafenamide (VEMLIDY ) (TAF)
Many MOA
What is Tenofovir usage?
Most poten with the lowest chance of resistance development
What is Entecavir MOA?
Selective guanosine analogue and potent inhibitor of HBV DNA
replication
What is the difference between TAF vs TDF?
TAF produces higher levels of TDF in the cells and can be administered in lower doses
What is the benefit of Entecavir?
More effective than lamivudine but should not be used to
rescue in lamivudine resistance (as may confer resistance)
When should combo therapy be used of HepB drugs?
People with cirrhosis who have resistance may have a flare,
which could be fatal
Lamiviudine+ Tenofovir for example
What is HepC?
Single stranded RNA virus
How is HepC transmitted?
Perinatal, sexual, blood
Which of the transmission is highest?
Parenteral
What is the symptomology of hepC?
Approximately 70% of patients are asymptomatic. If
symptoms occur, jaundice, dark urine, white stool,
abdominal pain, fatigue, fever, chills, loss of appetite, and
pruritus are possible.
What is the Sequelae of HepC?
chronic disease (75%; 25% spontaneously resolve), cirrhosis,
hepatocellular cancer 5%,
Accelerated presentation when co-infected with HIV
estimated that 70% of those in sask are co-infected with HCV
Which genotypes are most common in canada?
Genotype 1-6, 1a, 1b, 2, 3
What are the serological markers of HCV?
Anti-HCG
HCV RNA
What is anti-HCV?
(antibody to HCV): indicates infection, either acute
or chronic
What is the issue with the anti-HCV test?
- It may be negative during the first 6 weeks after exposure.
- Needs additional HCVRNA to confirm an acute infection.
- This test will remain positive for life despite clearance of infection.
What is the HCV RNA Test?
(HCV RNA by polymerase chain reaction):
indicates virus replication activity; it appe
What does the HCV RNA test mean?
Its presence indicates ongoing viremia whereas a negative result
indicates no active infection.
How often should individuals we screened?
annually with an anti-
HCV; if previously successfully treated or spontaneously cleared
the infection, HCV RNA should be performed
What was the traditional treatment of HepC?
Ribavarin and Interferon
What is Harvoni drugs?
Ledipasvir and sofosbuvir
Ledipasvir and sofosbuvir
Harvoni
What are the side effects of Harvoni?
Mild to moderate fatique, headache, insomnia, nausea
What is a limitation of harvoni?
Decreased absorption if administered with acid suppressing drugs (PPI)
What genotypes does harvoni cover?
G1,4,5,6
What is the drugs of Zepatier?
Grazoprevir and Elbasavir
Grazoprevir and Elbasavir
Zepatier
What is unique about Zepatier?
Studies targeting patients that are difficult to treat, or have
lack of data in literature(PWID, Renal) have been done
What drug is added to Zepatier to cover G3 paitents?
Sofosbuvir
What may occur when on Zepatier treatment?
Transient increase in ALT around 8 weeks and need monitoring
What genotypes does Zepatier target?
G1, 4
Who should avoid the use of Zepatier?
Decompensated Cirrhosis
What are the drugs in Epclusa?
Sofosbuvir and Velpatasvir
Sofosbuvir and Velpatasvir
Eclusa
What are the cure rates of Epclusa?
99-100%
What genotypes does Epclusa cover?
Pan-genotypic, some exceptions with G3 though
What conditions may require Ribavirin+Epclusa?
Cirrhotic and G3 where it is resistance testing Y93H
What drugs should be avoided when taking Epclusa?
Acid suppressing drugs
What is the drugs composed of in Maviret?
GLECAPREVIR + PIBRENTASVIR
GLECAPREVIR + PIBRENTASVIR
Maviret
What is unique about Maviret in terms of treatment?
May be used in severe kidney failure (Even dialysis), and patients who receive a Hep C kidney transplant
What are the special dosing recommendations of Maviret?
take with food
What is the coverage of maviret?
All genotypes 1-6
What is the drugs composed of in Vosevi?
SOFOSBUVIR + VELPATASVIR + VOXILAPREVIR
SOFOSBUVIR + VELPATASVIR + VOXILAPREVIR
Vosevi
What is the role of Vosevi?
Treatment failures
When should Vosevi be avoided?
Decompensated cirrhosis
What is the general treatment course of HepC drugs in general?
8-12 weeks
Which drugs should we focus on?
Harvoni, Zepatier, Epclusa, Maviret, Vosevi
What is the transmission of HepD?
Perinatal, sexual, blood
What protect us from HepD infection?
Vaccines for HepB
What is the treatment for HepD?
PEG INF for 12 months at standard dosing
What is Hep E?
Transmitted via fecal-oral, high mortality for pregnant women otherwise patients fare very well
What is the incidence of acute liver failure due to DIH?
50%
What is the general pattern of injury of liver damage?
Hepatocellular
Cholestatic
Steatosis
Mixed
What does Cholestatic mean?
Reduced bile development
What does steatosis mean?
Fat build up in the liver
What are the classifications of DILI?
By the damage generally
How is DILI diagnoses?
Generally by a temporal relationship with drug use
How would we identify DILI Hepatocellular?
– ↑ AST/ALT (preceds incr total bilirubin and ALP)
– Usually occurs w/in 1yr of starting drug
– Can result in fulminant hepatitis
How would we identify DILI Steatonecrosis?
– ↑ synth of FA→hepatocytes engorged with FA, burst open
– Inflammation
How would we identify DILI Fibrosis?
– Mild, chronic hepatitis→fibrosis→cirrhosis if drug not d/c
How would we identify DILI Fibrosis?
– Prevents proper elimination of bile by liver→accumulation
– ↑ ALP
What is the definition of hepatotoxicity>
ALT >3x the upper limit AND total bilirubin >2x the upper limit of norm
How do we calculate R?
What does an R value of >5 indicate?
Hepatocellular injury
What does an R value of between 2-5 indicate?
Mixed
What does an R value of <2 indicate?
Cholestatic injury
What are the intrinsic causes of DILI?
direct hepatotoxin, which has inherent propensity to induce
injury in all individuals; dose dependent or time dependent &
reproducible
What are the idiosyncratic causes of DILI?
causes injury in a small # of uniquely susceptible patients;
variable presentation
* further classified into allergic or non-allergic type
What re the toxic doses of Acetampinophen in adults?
7.5g
What are the toxic doses of acetaminophen in children?
> 150mg/kg
What do we consider when DILI is suspected?
Considera ll sources
