Liver Disease and Transplantation Flashcards
Rates of fulminant hepatic failures in HAV, acute HBV, and HBV and HDV coinfection
HAV = 0.1%
Acute HBV = 1%
HBV and HDV Confection = 20%
Percent of individuals who develop chronic HBV when exposed perinatally? When exposed in childhood? When exposed in adulthood?
How about chronicity in patients exposed to HCV?
Chronicity is 90% when exposed perinatally, 50% if exposed during childhood, and 5% in adulthood.
HCV becomes chronic in 60-85% of patients exposed regardless of age.
When to screen HBV carriers without cirrhosis for HCC?
Africans >20, Asian males >40, asian females >50, family history of HCC
2 extrahepatic complications of chronic HCV? How to improve symptoms?
Essential mixed cryoglobulinemia, membranoproliferazive glomerulonephritis (MPGN).
Can improve renal function and proteinuria with eradication of HCV RNA.
Extrahepatic manifestation of chronic hepatitis B infection? How to improve symptoms?
Polyarteritis nodosa (positive for HBsAg).
Can improve symptoms with antivirals, as well as mortality.
HBV genotype that is most responsive to peginterferon? Least responsive
Most responsive is genotype A with high ALT or low HBV DNA.
Least responsive is genotype D.
Symptoms of chronic HBV spontaneous seroconversion
Where HBeAg is suppressed by immune system, HBV DNA is lost, and HBeAb appears. Can cause elevations in AST/ALT and sometimes acute liver failure. These patients can still get HCC, but not cirrhosis
Risk of fulminant liver failure from HEV?
Very low, less than 1% but as high as 15-25% in pregnant women
HCV genotype most likely to progress to cirrhosis?
Genotype 3
Most challenging HCV genotype to treat? How to treat more effectively?
Genotype 3 is the most challenging to treat. Can treat most effectively by increasing therapy to 24 weeks.
What is the risk of recurrent HCV after transplant?
25-33% of recurrent HCV patients after transplant can develop fibrosis or cirrhosis again.
What are the features and lab tests for Type II AIH?
Autoimmune hepatitis which is rapid onset usually seen in children under 14. Test for Anti-LKM
Most common cause of drug-induced autoimmune hepatitis? How to treat?
Nitrofurantoin and minocycline
Cause interface hepatitis and abundance of plasma cells
Stop drug, sometimes will need acute course of steroids
Which beta blocker is best for variceal ppl during pregnancy?
Propranolol
Management of HEV in solid organ transplant?
Reduction of immunosuppression, if that doesn’t work, then ribavirin
Ribavirin major side effect
Hemolytic anemia (dose dependent)
Treatment options for HCV in patients without cirrhosis
Glecaprivir/pibrentasvir for 8 weeks (Mavyret)
Sofosbuvir/velpatasvir for 12 weeks (Epclusa)
Ledipasvir/Sofosbuvir for 12 weeks (Harvoni)
Difference between treating HCV in patients with compensated cirrhosis and without cirrhosis?
None, can still use Glecaprevir/pibrentasvir for 8 weeks, though need to increase to 12 weeks if connected with HIV.
Can still use sofosbuvir/velpatasvir for 12 weeks.
Can still use ledipasvir/sofosbuvir for 12 weeks.
Critical lab test to check before starting HCV therapy? Why?
HBV serologies because risk of HBV reactivation increases with DAA therapy, even for patients who are core positive.
How to treat HCV in patients with decompensated cirrhosis?
Need to increase duration of treatment in most cases, consider addition of ribavirin, and start transplant eval because may be beneficial to transplant before tx
Do you need to dose-reduce DAAs for HCV in patients with CKD
No
Should you treat acute HCV?
Monitor HCV q4-8 weeks for up to 12 months to determine if spontaneous clearance occurs.
How to treat chronic hepatitis D infection?
PEG-IFN alpha for 12 months, can also add Bulevirtide
How to prevent HBV infection in transplant recipients?
All HBsAg positive patients undergoing transplant should receive entecavir, TDF, or TAF, with or without HBIG
How to treat HBsAg negative patients who receive HBsAg negative, HBcAb positive donor livers?
Long term prophylactic antivirals with entecavir TDF or TAF
How to diagnose CMV hepatitis?
Biopsy is needed
Which patients are most susceptible to HSV hepatitis?
Immunosuppressed patients or pregnant patients in 2nd or 3rd trimester
How to treat HSV hepatitis
IV acyclovir is preferred, start before diagnosis is confirmed because delay can be catastrophic
Which drugs require prophylaxis for HBV reactivation?
Very high risk: Rituximab and stem cell transplant
All others just require monitoring with HBV DNA.
High risk: >20mg pred, cytokine inhibitors
Moderate risk: Chemotherapy, antiTNF, anti rejection meds
Low risk: Azathioprine, methotrexate
3 groups for which to treat chronic HBV
- Cirrhosis and low viremia (<2000)
2.HBeAg+ immune-active if HBV DNA >20,000 and ALT >2x ULN - HBeAg- Immune-active if HBV DNA >2000 and ALT > 2x ULN
Why is TAF superior to TDF
Decreased chance of bone and renal abnormalities
When to stop oral meds for chronic HBV with HBeAg+
12 months after seroconversion from HBeAg to HBeAb
Lifelong if no seroconversion
When to stop oral meds for chronic HBV with HBeAg-?
With 3 years of viral load suppression if they can be monitored closely
Microvesicular steatosis vs Macrovesicular steatosis
Microvesicular steatosis seen in rare conditions (Reye syndrome, mitochondrial disorders, drug toxicity [tamoxifen, amiodarone, methotrexate])
Macrovesicular steatosis seen with NAFLD and alcoholic steatosis
Features of alcoholic hepatitis on pathology
Ballooning degeneration, apoptosis, giant mitochondria, mallory bodies (not specific).
Damage most prominent in perivenular region
Presentation and treatment for acute Wilsonian hepatitis
Elevated LFTs, jaundice, hemolysis due to copper
Transplant
How to diagnose hemochromatosis?
Ferritin, transferrin saturation, hemochromatosis genetics.
BUT ultimately liver biopsy IS necessary
Features of metabolic syndrome
High visceral fat, dyslipidemia, insulin resistance, hypertension
Waist circumference
Fasting triglycerides >150
HDL <40
BP>130/85
Fasting BG >110
Likely cause of elevated ALT if no obvious cause
75% of these patients will have NASH
Acute Fatty Liver of Pregnancy presentation, cause, and treatment
Rapidly progressive rise in AST/ALT, diffuse micro vesicular steatosis. Can cause liver failure. Caused by toxic intermediates of fatty acid oxidation. Need immediate termination of pregnancy and sometimes transplant
Difference between Dubin-Johnson and Rotor Syndrome
Both cause conjugated hyperbilirubinemia, liver turns black in Dubin-Johnson syndrome
PFIC
Progressive familial intrahepatic cholestasis can cause cirrhosis in infancy. Likely will need transplant
BRIC
Benign recurrent intrahepatic cholestasis. Intermittent, non progressive, normal liver function
CF associated liver disease, and treatment to delay progression
Causes progressive cholestasis due to thick bile, can give patients ursodiol, can progress to biliary cirrhosis
Hereditary Tyrosinemia Type 1 and treatment
Enzyme missing leading to toxic intermediates in pathway of phenylalanine and tyrosine metabolism. Causes childhood fibrosis and cirrhosis. NTBC inhibits early step in pathway and can be used for treatment. Some patients may need transplant.
Glycogen storage diseases and hepatic consequences
Type 1 (Von Girke)
Type 3 (Cori)
Changes in G6P (type 1) and debranching enzyme (type 3)
Causes hepatic adenomas and HCC
Some can have ALF and require transplant
Gaucher Disease
Lipid storage disease (glucocerebrosidase deficiency). Most common deficiency in jews
Causes hepatosplenomegaly, bone fractures, anemia, thrombocytopenia
Some patients can develop progressive fibrosis and portal hypertension
Role of hepcidin
Hepcidin regulates iron release from macrophages and intestinal absorption by binding to ferroportin in enterocytes
What manifestations of hemochromatosis usually don’t improve with chelation of phlebotomy
Testicular atrophy and arthropathy
Risk of HCC does not improve either
What does ATP7B do?
Secretes copper into bile for excretion. Mutation causes Wilson disease
How to diagnose Wilson disease?
Check ceruloplasmin, if low, eye exam and 24h copper extretion
How to treat Wilson disease
Copper chelation with Trientine and prevent absorption with oral zinc.
Can also use d-penacillamine but has side effects
Treatment for ALF due to wilson’s
Transplant, if normal ATP7B in graft then chelation is not needed
A1AT Alleles
M is normal
S is modest deficiency
Z is severe deficiency
MM normal
ZZ is severe deficiency, SZ also relatively severe
Diseases that often accompany PBC?
Sjogrens Syndrome, CREST.
Inflammatory destruction of small bile ducts causing cholestasis and biliary cirrhosis.
PBC presentation
Elevated AP, pruritis, fatigue, xanthomas/xanthelasmas, fat soluble vitamin deficiencies
Treatment of PBC
13-15mg/kg ursodiol or OBCA for ursononresponders
Histology of PBC
Florid duct lesion
How to diagnose AIH?
Serologies are helpful but need to biopsy to confirm
AIH histology
Plasma cell infiltration, interface hepatitis
How to treat AIH
40-60mg pred, transition to 1.5-2mg/kg azathioprine
can also use mycophenolate or tacrolimus
Which treatment for AIH cannot be used in pregnancy?
Mycophenalate
Presentation of acute cellular rejection
Elevations in transaminases and alc phos weeks to months after transplant
What condition has hepatocyte injury, ductulitis, venular Endothelitis?
Acute cellular rejection
How to treat ACR?
Mild: Conservative
Severe: IV steroids and anti-lymphocyte globulin
What condition usually follows ACR?
Chronic ductopenic rejection – marked by progressive loss of bile ducts
Schistosomiasis causes…
isolated pre-sinusoidal portal hypertension
ABCB11
Gene implicated in BRIC PFIC and intrahepatic cholestasis of pregnancy
Jaundice and transaminase elevation in the setting of chemotherapy or bone marrow transplant?
Hepatic sinusoidal obstruction syndrome
Cholestasis with hilar biliary structures in a patient with a history of shock
Ischemic cholangiopathy
An insulin sensitizing peptide secreted by adipose tissue whose levels decline as fat accumulates, low levels characterize metabolic syndrome
Adiponectin
A phospholipase enzyme associated with the propensity to hepatic steatosis and fibrosis in both NASH and alcoholic liver disease
Adiponutrin
A circulating signalling peptide that participates in the up regulation of hepcidin production
Bone morphogenic protein 1
Hepatic co-receptor for bone morphogenic protein 1
Hemojuvelin
What is the antibody against the lipoid antibody moiety of the pyruvate dehydrogenase complex in bile duct epithelial cells
Anti-mitochondrial antibody
What is the antibody against hepatic enzyme cytochrome P450 2E6
Anti liver kidney microsomal antibody (AIH type 2)
How to calculate HVPG? What is considered elevated
Hepatic wedge pressure - free hepatic pressure. More than 5 is elevated, varies tend to happen over 10
Paradigm for primary prevention of varices
Look at liver stiffness and platelet count. If PLT >150,000 or liver stiffness <20, no need for primary prevention.
If LS>20 and platelet <150K, or LS>25 then start NSBB.
If not tolerated, do EGD. If no varices, EGD q2y. If large varices, band.
Important treatment of variceal hemorrhage
CTX 1g/day for up to 5 days
Octreotide
PPI is not important if variceal bleed
GOV1 vs GOV2 vs IGV1 vs IGV2?
GOV1 extend along lesser curve
GOV 2 extend from esophagus to the fundus
IGV1 are isolated in the fundus
IGV2 are in the antrum
Which patients benefit from early tips and variceal bleeding?
CP C after hemorrhage or CP B with active hemorrhage
How to treat portal hypertensive gastropathy
Iron and beta blocker
Two different types of high SAAG (>1.1) ascites?
Portal hypertension (low ascites albumin <2.5)
Cardiac ascites (higher ascites albumin >2.5)
Who should be on SBP ppx? What to use
Those who have ever had SBP – use cipro
What causes persistent encephalopathy in patients that are otherwise compensated?
Splenorenal or other shunt
How to diagnose hepatic sarcoid
Biopsy
Hepatopulmonary syndrome cause, presentation, treatment
Caused by dilated pulmonary capillaries and shunting causing hypoxemia. Presentation is platypnea and orthodeoxia.
Tx with transplant
Portopulmonary hypertension
Pulmonary vasoconstriction due to unprocessed mediators from splanchnics causes severe pulmonary hypertension
Typical imaging features of HCC?
Arterial hypervascularity and early washout in venous/portal/delayed phase
How to treat early stage HCC in healthy patient?
Resection if single mass <5cm is curative
Otherwise will need RFA +/- TACE or TARE
Milan criteria
Patients can be transplanted for HCC if they have 3 or fewer tumors <3cm, or 1 tumor <5cm provided no vascular invasion or extra hepatic disease
What must be included in transplant workup for HCC patients?
CT chest and bone scan
How to treat advanced stage HCC in Childs A or B patients?
Atezolizumab/bevacizumab»_space;> sorafenib
How to treat advance stage HCC in Childs C patients?
Supportive care, median survival is 3 months
What is the MELD to consider TXP?
15, but patient should be referred to txp center after their first decompensation
Does AIH recur post transplant?
Yes – do not taper steroids completely
What are the signs of primary liver graft nonfunction?
No bile production, liver failure, renal failure
What causes hepatic venous outflow obstruction after transplant?
Stenosis of the anastomosis of the hepatic vein and the IVC
What is the baseline IS regimen after liver transplant?
A CNI (tac/cyclo), immunomodulator (MMF, everolimus, azathioprine), and steroids
What is long term IS regimen after liver transplant?
Tacrolimus
Why is an immunomodulator added to the baseline IS regimen?
To reduce doses of the calcineurin inhibitor (tac/cyclo) and prevent nephrotoxicity
What is the colonoscopy interval for post liver transplant patient with UC/PSC
Every year
Should you treat HBV with cirrhosis?
Yes Always treat
