Liver Disorders Flashcards
Liver related tests and scores?
Markers of hepatocelullar injury (AST, ALt, Ali Phos)
Markers metabolic function: Total Billirubin
Test of synthetic function: PT, Albumin
Test for Liver fibrosis:Fibroscan, AST Platelet Ratio Index (APRI score), Magenetic resonance Elastography
Child-Pugh: Liver function in cirrhosis patients
MELD score assess severity of ESLD and used for organ transplant allocation
Madder discriminates function score: Prognosis of alcoholic hepatitis and decide on steroid treatment
How should elevated liver enzymes be worked up?
- If liver enzymes are > 5 times the ULN with signs and symptoms then evaluate immediately
- If 3-5 times upper limit of normal without sign and symptoms repeat in 1-3 months
- If < 3 without symptoms repeat in 3-6 months
Elevated Alkaline phosphatase workup?
Determine where is it coming from with a GGT or fractionated alkaline phosphatase
If the increase is from liver GGT will also be high
Once we confirm the increase Alk phos is hepatic in origin next step is to do U/S of Liver
If the U/S shows dilated ducts next is MRCP/ERCP
If U/S is normal order Antimitochondrial antibody testing, if positive consider primary biliary cholangitis and liver biopsy should be done. If its negative consider MRCP
how to work up elevated ALT and AST?
- Hepatitis screen
- U/S to look for fatty liver
- ANA/Anti Sm Ab to look for autoimmune hepatitis
- Tranferrin saturation and ferritin
If these test are negative (do second level tests)
Then check Alpha 1 antitrypsin, Ceruloplasmin, Antibody screening for celiac disease
What are the causes of unexplained ALT elevation?
Celiac Disease
Thyroid dysfunction
Muscle disorders
Adrenal Insufficiency
Degree of ALT elevation can help with possible underlying etiologies?
- NAFLD and Alcohol: 40-150
- Alcoholic hepatitis causes AST >ALT 2:1 and AST is typically < 300
- Acute Viral Hepatitis 500-2000
- Autoimmune hepatitis: 200-2000
- Chronic Viral Hepatitis: 40-200
- Drug induced- 200-1500
AST/ALT> 1000 think acute viral hepatitis, drugs, shock liver, autoimmune hepatitis, buds chiari, CBD
What is the MCC of Liver Failure in the US
What scoring system is used to diagnosed it?
Drug Induced Liver Injury (DILI)
CIOMS RUCAM score
What is the mcc cause of direct drug induced liver failure
What drugs cause idiosyncratic liver failure?
Acetaminophen (direct)
Amoxicillin/Clavulanic acid (idiosyncratic) (MCC of DILI in the US)
What is the MCC of Asx liver enzyme elevation?
NAFLD
What is the spectrum of NAFLD?
Steatosis (macrovesicular steatosis in hepatocytes)—>Steatohepatitis (NASH)—>NASH + Fibrosis—>Cirrhosis
Note: AST, ALT can be normal in both NAFLD and NASH
In all patients with NAFLD, what should patient be assed for?
Patient should be assess for Fibrosis because it is the most important predictor of liver mortality in NAFLD
We can assess with APRI score
What is the mcc of death in NAFLD patients?
Cardiovascular death
What’s considered significant alcohol intake?
Men >21 standard drink/ week
Women >14
What’s NASH?
(NASH, this is hepatic steatosis plus neutrophil, lymphocytic infiltration with hepatocellular injury around the central veins in association with Mallory bodies, and pericentral/peri sinusoidal fibrosis
Treatment of NAFLD
NO FDA proved meds
Statins are safe and reduce CVD risk
Bariatric surgery resolves NASH in 60-80 % of patients and may improve fibrosis
Liver biopsy is done in what high risk patients with NASH?
Age >50 DM HTN Female Obese AST>45 AST/ALT ratio >0.8 Thrombocytopenia
If Liver Bx shows just fatty liver decrease calorie intake to 500 kCal/day, increase mono and polyunsaturated fatty acids in the diet, and exercise
What is the leading cause of crypto genie cirrhosis in the US?
NASH
What are the 4 types of inherited bilirubin disorders?
Unconjugated:
- Gilbert Syndrome: defective hepatic uptake of bilirubin
- symptoms are apparent during periods of fasting with increased billirubin
- Phenobarbital decrease the billirubin
- DD is hemolysis; however, Rec count is increased in hemolysis and NL in Gilbert
- No treatment needed - Crigler-Najar- seen at birth
Conjugated:
- Dublin-Johnson- black liver
- Rotor syndrome (Liver is not pigmented)
In a patient with isolated increase in indirect billirunin without increase AST/ALt or Alk phos what test should be ordered next?
Reticulocyte count to differentiate between hemolysis and Gilbert
How does alcoholic hepatitis present?
How is it treated?
Leukocytes is
Fever
RUQ pain
GGTP is usually elevated
Treatment:
Calculate MAddrey discriminators function score
What is MAddrey discriminators function score equation and how is it used in alcoholic hepatitis treatment?
DF= (Patients PT- control PT) x 4.6+ patient’s bilirubin
If DF is > 32 mortality is 50%
In patients with alcoholic hepatitis + DF >32 with or without encephalopathy treat with Prednisolone 40 mg for 28 days
In patients with alcohol hepatitis with high DF when should prednisolone not be given?
Concomitant GI bleed, Active infection, Renal Failure, or Pancreatitis
How is Post exposure prophylaxis done for Hepatitis A
Which patient population is Hep A vaccination recommended
PEP with Ig and Vaccine within 2 weeks of contact
Vaccine recommended for people with chronic liver failure
Clinical progression of Hep B?
Starts as acute hepatitis with constitutional symptoms, malaise, arhtralgia, nausea, loss of appetite this can last 1-4 months
Majority of adults who get acute hepatitis (90-95%) have complete resolution
5% develop chronic hepatittis, can progress to cirrhosis
5% are carriers
<1% has fulminant hepatitis
What serology do we see in Hep B infection during the presymptomatic prodrome phase?
Early (presymptomatic) Prodrom phase
HbSAg= you are producing the virus
HBeAg=infectivity
HBDNA= detected by PCR during acute infection and in chronic infection with replication
What is the serologic test of choice when patient present with Acute SYMPTOMATIC Hep B infection?
HBcAb IgM
What are the 2 types of HBcAb?
HBcAb IgM= Seen in the Window period, During acute infection, and doing flare of chronic hepatitis
HBcAb IgG=BEst marker for previous infection
What serology in Hepatitis B denotes vaccine or immunity
HBsAb
If we see both HBcAg IgG and HBSAg then the immunity is due to past exposure
How should you workup a patient with positive Hep B surface antigen
Order Hep D DNA, HBeAg, HBeAb (antiHBe), and ALT
Asymptomatic patient with:
HbSAg (+), DNA (+), Increase ALT, HBeAg (+), HBeAb (-)= Chronic Hep B and should be treated
HbSAg (+), DNA (+), Increase ALT, HBeAg (-), HBeAb (+)=REactivation and should be treated
HbSAg (+), DNA (+), normal ALT, HBeAg (+), HBeAb (-)=High infectivity carrier, Monitor
HbSAg (+), DNA (-), NL ALT, HBeAg (-), HBeAb (+)=inactive carrier, low infectivity , monitor
How should you workup a patient with negative Hep B surface antigen
HBSAg (-), HBSAb (-)=Vaccinated not exposed
HBSAg (-), HBSAb (+) HBcAb (-)=immune due to vaccination
HBSAg (-), HBSAb (+) HBcAb (+)= past infectious and immune
What is the preferred treatment for Hepatitis B
how long is treatment continue for?
Interferon alpha
Entecavir
Tenofovir
Oral agents are given until one of the following:
HBeAg or HBSAg seroconvert to HBeAb or HBsAb
Intolerable side effects
Ineffectiveness
Resistance
Most guidelines say may discontinue after 1 year for HBeAG (+) if DNA is undetectable and HBeAG seroconversion to HBeAb occurs
The risk for reactivation is based on what?
Core Ab positivity Surface Ag (+) or (-)
-Very high risk of reactivation in patients with:
HBSAg (+) and on anti CD 20 (rituximab)therapy or stem cell transplant
-High risk
HBSAg (+) and taking prednisone > 20 mg or anti CD 52 (Alemtuzumab)
-Moderate risk
HBSAg (+) and chemotherapy without prednisone, anti-TNF or post solid organ transplant
So patients on Steroids, Rituximab, Alemtuzumab, TNF Alpha, Stem cell transplantation, SOlid organ transplant SCREEN FOR HEP B
PTIENTS SHOULD START TENOFOVIR OR ENTECAVIR if moderate to high risk before starting immunosuppressive therapy and should continue for 6 months thereafter and 1year thereafter for rituximab
Before treating patient for hepatitis C what should be checked?
HbSAg and if positive treat with Tenofovir or Entcavir prophylactically prior to starting hep c treatment
Post exposure prophylaxis of hepatitis B?
- Sexual exposure or household contact to acute HBV=Ig and Vaccination
- Sexual exposure or household contact with chronic carrier=vaccine only
- Percutaneous or mucosal exposure=Ig and Vac
- Perinatal exposure= Ig and Vaccine
What are the extrahepatic complications of HBV that require antiviral therapy?
Polyarteritis Nodosa
Membranous Glomerulonephritis
Who should be screen for Hep C?
Everyone age 18-79 should be screened once for Hep C with Hepatitis C antibody regardless of risk factors
If antibody is positive we then check viral load
To check for suspected reinfection of hepatitis C what test should be ordered?
HCV RNA only
What does (+) HCV Ab and negative HCV RNA indicate
REsolve infection
False positivity
Passively acquired or low level of viremia
What is the definition of chronic hepatitis?
Elevation of ALT for more than 6 months
Management of chronic HCV?
Abstinence from alcohol, check HIV and HBV
Evaluate patient for Fibrosis with liver biopsy
Check for HAV and HBV and if negative give vaccine
What are the 2 types of autoimmune hepatitis?
Type 1=MC seen in females mostly
- Associated with (+) ANA and Anti-Smooth muscle antibody
- Treated with prednisone and Azathioprine
Type 2=Associated with anti LKM antibody and Anti liver cytoskeleton antibody
- seen mostly in children and very rarely in adults
- less responsive to steroids
What are the features of autoimmune hepatitis?
Bimodal age distribution
Elevated ALT, AST between 1–20 and 45-70
Patient present with fatigue , abdominal pain, itching, decreased appetite, myalgia, diarrhea are common symptoms
Patient CMP usually show high total protein but low albumin so The gamma globulin level is high SO you get a Hypergammaglobulinemia
What is the diagnostic criteria for autoimmune heapatitis?
- Presence of autoantibodies
- ANA (1)or Anti-SMA (2 points)
- Anti-LKM (2)
- Anti SLA (2) - IgG or Hypergammaglobulinemia (2)
- Hystology compatible (1-2)
- No viral hepatitis (2)
> 7= definite AIH
6=Probable AIH
What is the definition of Fulminant hepatic Failure? And what are the types?
Acute liver injury with hepatic encephalopathy
2 types:
Hyper acute= when liver injury progresses to encephalopathy within 1 week
Subacute when <12 weeks
What is the most common cause of fulminant hepatic failure
Acetaminophen overdose
even moderate Tylenol dose in an alcoholic patient can lead to it
Regularly alcoholic hepatitis should have AST and ALT less than 300 if AST is high >400 patient should be worked up for Tylenol toxicity or viral hepatitis
What are the complications of fulminant hepatitis?
Cerebral edema (mcc of death ARDS Renal failure Hypoglycemia Sepsis (mcc of death) Coagulopathy
When patients present with fulminant hepatitis they should be transferred to a transplant center
What is the typical presentation of Primary biliary Cholangitis?
Disease of the Interlobular bile ducts, seen mostly in women
Present with Fatigue, Pruritus, Xanthelasma due to hyperlipidemia
Jaundice, steatorrhea
Labs show: elevated Alkaline phosphatase and Anti-mitochondrial Ab
U/S wont show dilated ducts
Note if AMA is negative in woman or prior to diagnosing PBC in men cholangiogram (MRCP) is done to rule out Primary sclerosis’s good cholangitis
What is an important extrahepatic complication of primary biliary cholangitis?
Osteoporosis
What is the treatment of primary biliary cholangitis?
Pruritus= hydoxizine, lubrication, cholestyramine
Ursodiol=slows disease progression
At Child Pugh B score place patient on transplant list
Obeticholic acid is given if patient doesn’t not respond to Ursodiol or in combo with it or a mono therapy if patient cant tolerate ursodiol
How does Primary Sclerosing cholangitis present?
Diffuse fibrosis inflammatory disease of the biliary duct
Commonly seen in men
Associated with Ulcerative colitis (80%)
P-ANCA positive as well ass ANA and ANti SM
So when Alk phos is elevated in a male MRCP should be done
what does MRCP show in Primary sclerosing cholangitis?
Narrowing and dilation of the biliary tree
If MRCP shows biliary obstruction then ERCP is done to make sure there’s no cholangiocarcinoma
If PSC is suspected and cholangiography is negative follow it up with biopsy for possible small duct PSC
What are the complication of Liver Cirrhosis?
In cirrhosis there is elevated portal pressure the normal pressure gradient between the portal vein and hepatic vein is 3-6 mmHg
> 6 is considered Portal HTN
Ascites develop at gradients > 10
Esophageal Varices occur at gradients >10and bleed at > 12
-Cirrhotic patient should be screened every 2-3 yrs with EGD
What are the diet recommendations for cirrhosis patients?
- Diet to achieve a BMI of 20-25
- Vitamin D supplement
- Protein restriction is no longer recommended because there is defective gluconeogensis so muscle are broken done during the night for energy. So these patients are recommended to be on 1.2-1.5 gram/kg of protein per day every if there is hepatic encephalopathy
- cirrhosis and elevated PT/INR does not confer protection against VTE and hospitalized patients should be prophylactically treated unless INR>3
- Avoid Narcotics, Benzos and NSAIDS in cirrhosis patients
- consider trazodone or hydroxyzine for insomnia
What does SAAG indicate?
> 1.1=portal HTN= Cirrhosis, RHF, Budd chiari
<1.1=nephrotic syndrome, malignancy, TB
Treatment of Ascites?
-Salt Restriction of 2g per day
A 24 hr urine sodium > 90 indicates noncompliance
- Water restriction only if sodium is <125
- No protein restriction
Spirinolactone + Lasix.
Midodrine can be added if patient have diuretic resistant ascites in association with hypotension
what medication worsen surgical in refractory ascites?
BB
ACEI/ARB they decrease renal perfusion they should be stopped when cirrhotic patients develop hypotension
what 3 scenarios in a cirrhosis patient do we need to stop BB?
- Refractory Ascites
- Cirrhosis patient with Hypotension (<100)
- Even One occurrence of SBP (BB d/c permanently)
Once BB is stopped Banding should be considered for Varices
When is therapeutic paracentecis perform for ascites?
- Symptomatic large ascites
- Ascites unresponsive to diuretics
When > 5L of ascetic fluid is removed give patient 25g Albumin per %L of ascetic fluid
What therapy is available for refractory ascites?
Peritoneal venous shunt and TIPS
Midodrine (may improve renal function)
What intervention have been shown to improve transplant free survival in cirrhosis patients?
TIPS
When should IV albumin be given in a patient with SBP?
IV 25% albumin should be given when:
Creating is >1
BUN >30
Or
Billirubin total is >4
(1.5g/kg is given at diagnosis and 1 g/kg on day 3)
What medication do we use for prophylaxis against SBP?
Cirrhosis patients with Variceal bleed should get IV Ciprofloxacin to prevent SBP
Patients with history of SBP get with Norfloxacin or Bactrim
What are the indication primary prophylaxis against SBP with Nofloxacin?
Cirrhosis patients with
Ascites with fluid protein <1.5 g/dL
Impaired renal function
Serum Sodium <130
Child Pugh >9
How doe we diagnose Hepatorenal syndrome?
Patient with cirrhosis and ascites with a serum creatinine >1.5 mg/dL we stop their diuretic and give them IV Albumin if no improvement of the creative after 2 days of stopping the diuretic
Typically Urine sodium is <10
What are the 2 types of Hepatorenal syndrome?
Type 1:Develops rapidly and usually precipated by GI bleed or infection
Type 2: more slow onset, seen in patient with persistent ascites
How is Hepatorenal syndrome treated?
Type 1= Midodrine+ IV albumin +Octreotide
Type 2= liver transplant
What is portopulmonary HTN?
how is it treated?
what is Hepatopulmonary syndrome?
This is Pulm Arterial HTN in patients with portal HTN and no other etiology
Treated with sildenafil, epoprostenol, bosentan
Liver transplant is done for patients with Pulm artery pressure <50 mmHg
Hepatopulmonary syndrome is seen in advance liver disease with hypoxia (PaO2 <80) or AA >15mmhg; patient complains of platypuses (oxygenation improves lying flat), Orthodeoxia
Hepatopulmonary syndrome is Dx by what?
Echo with bubble study and is positive if we see bubbles in LA after 4-5 cardiac cycles or macroaagregated albumin NM Scan
Primary prevention of variceal bleeding is?
No selective BB )propranolol or nadolol)
If pt cant tolerate BB because of hypotension then endoscopic band ligation can be done
BB blocker do not prevent formation of Varices its just prevent them from bleeding once they already form
what medication can we use for treatment of hepatic encephalopathy
Lactulose and Riifaximin
who do we screen for HCC?
What screening modality are used
- Hep B patients with one of the following :
- Asian male >40
- Asian Female >50
- African American >20
- Hep B with cirrhosis
- Hep with fhx HCC - Cirrhosis of any etiology
U/S every 6 months
If U/S not available then AFP
How does HCC present?
RUQ pain, Weight loss, Ascites
A serial triphasic CT that shows a lesion with enhancement during arterial phase alongside elevated AFP is enough to Dx without getting biopsy
how is HCC. Treated?
Solitary lesion < 5 cm or <3 lesions each < 3cm=liver transplant
When to refer patients for liver transplant?
MELD >10
Child Pugh >7
Evidence of decompensated cirrhosis: AScites, SBP, Encephalopathy, Variceal bleed
