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Conferences and Medical Updates

HBV, NASH, HCC

ACUTE ON CHRONIC LIVER DISEASE
1.    ACLF : Acute decompensation of cirrhosis resulting in liver failure (jaundice or elevated INR and associated with extra hepatic organ failure with high short term 4 weeks and 3 month mortality.  It is in 3 grades
2.    Ppt factors are alcohol, HDV, HBV reactivation, dili, GI bleed, infection, ischemia, and portal vein thrombosis precipitates it.
3.    Def – when 2 extra hepatic organ failure ( shock, grade 3 HE or dialysis or ventilation).
4.    European def is
a)    Grade 1 AKI requiring HD or single organ damange 22% mortality
b)    2 organ damage is grade 2 32% mortality
c)    3 organ damange is grade 3 78% mortality
5.    Liver failure if bilirubin is 5 mg and INRO more than 1.5 by Asian def.
6.    EASL def by CANONIC study – Cr more than 2, bili more than 12, INR more than2.5, plt less than 20 or 3-4 for stage HE, need for pressures or Pa02/Fio2 ratio less than 200.
7.    ACLF stage 2 or 3 withdraw care candidates. Best time to prognostic between days 3-7.
8.    CLIF consortium organ failure score www.clifconsortium.com
9.    CLIF-sofa score for alcoholic cirrhosis pt.
10.    Immune dysfunction in ACLF leads to sepsis.  Bacterial translocation, endotoxemia and then reduced immune response and reduced albumin function.
11.    Management is identification of SBP, treat in ICU, plasma expansion with albumin, airway protection and transfer to transplant center.
12.    Liver support devices  : plasma exchange dialysis, or albumin dialsys.  Benefit was only in pt more than 30 MELD.
13.    Neupogen or erythropoietin may help in some patients.  Simultaneous liver-kidney transplant is a thought.

HCC

·         2 cm HCC patients get MELD exception
·         Sorafenib – no difference between placebo.  STORM trial
·         Local resection – depends on portal HTN (has to be low), 50% of liver has to be functional, low platelet is CI and number of lesions.  So, has to be MELD less than 10, platelet more than 150, portal pressure less than 10
·         Local therapy – DEB-TACE, Y90, cryoablation, RFA, microwave, IRE
·         RFA fails due to vasculature that dissipates heat (if 3 mm vessel).  Microwave obviates it (no heat sink issue).  Multiple probes needed and multiple needed so not comfortable for patients
·         Image guided transcatheter tumor therapy – TACE.  Preferred IR method.  Now they go to segmental artery and deliver chemotherapy.
·         Y90 radioembolization (beta emission so not radioactive). Works great in patients with portal thrombosis
·         MELD exception for HCC – Milan criteria.
·         Salvage liver transplant – done in france.  Resect first then wait for OLT available
2013
Hepatitis B
Hep Be Ag neg Hepatitis and Hep B reactivation
80% of CHB is imported from a foreign born person
More than 60% are unaware of the disease
A, B, C, D, E incidence 18, 36, 32, 8 and 3 percent
e Ag neg is 25% and e Ag positive CHB is 13%.
Inactive HBsAg carrier state less than 2000 IU/ml
Immune tolerance is HepBeAg positive with more than 10 raised to 8 copies per ml
Indeterminate hep B are 13% – elevated Hep B titers, but normal ALT
Interferon treatment is 60 weeks.

Mayo Clinic

Hepatitis B

  • Types  Hep B e Ag positive (and high DNA, high ALT), Inactive carrier (neg Hep B e, normal ALT, low DNA), Hep B e Ag neg chronic hepatitis( slightly high DNA, abnormal ALT, precore mutation)
  • 7 drugs, limousine, adefovir, entecavir, telbivudine, tenofovir, and 2 types of PEG
  • Under evaluation are emtricitabine, clevudine, valtorcitabine and combination treatment
  • So far, combination treatment with limousine is not better
  • .Can effectively change from adefovir (hepsera) to viread (tenofovir)
  • Mnemonic TV (tenofovir is viread), BE (baraclude is entecavir)
  • Newer drugs for hepatitis B are better
  • Guidelines based on DNA level of more than20,000 on adult acquiring Hep B and more than 2000 for young or childhood acquired Hep B DNA
  • Current guidelines are if DNA less than 20,000 IU/ml, normal ALT, and Hep B e Ag Pos no treatment and monitor every 6 to 12 months.
  • DNA more than 20,000, hep B e Ag pos, normal ALT, consider liver biopsy.  Treat if fibrosis or hepatitis treat with baraclude or viread or PEG
  • If DNA more than 20,000, ALT elevated and Hep B e AG pos, treat.
  • If Hep B e Ag neg patients use HBV DNA level of 2000 as cut off.   If ALT neg and less than 2000 observe ever 6 to 12 months.  If more than 2000 and normal ALT consider liver bx
  • If more than 2000, ALT elevated and treat. (and hep B e ag neg)
  • If patient has compensated cirrhosis, HBV DNA more than 2000, treat.  If DNA less than 2000 do not treat.  Irrespective of ALT.  DO NOT — USE PEG.
  • If decompensate cirrhosis, hepatitis B positive treat irrespective of DNA, or hep B e Ag pos or neg. Use Viread or baraclude
  • If patient is resistant to lamuvidine, do not use baraclude. (high incidence of resistance develops eventually).
  • Genotype B more likely to respond to PEG, ALT > 100 for 48 weeks
  • Immune tolerant pts, less than 35, normal ALT, Hep B e Ag positive, Very high HBV DNA more than a million IU/ml should be watched!
  • Immune active have abnormal ALT, HBV DNA more than 20,000 and should be treated
  • Immune control : normal ALT, HBV DNA less than 20,000 and no inflammation. No treatment.
  • Immune escape : abnormal ALT, HBV DNA more than 10,0000, pre core mutant, inflammation plus fibrosis and Hep B e Ag neg.
  • Check HDV in IVDA, hemophilic pts.  Less likely in Asians.
  • Anyone going on immunosuppressant’s or anti TNF will need treatment for Hep B.
  • Anti Hbc alone positive.  Repeat lab.  Usually false positive.  It can mean window phase or late immunity.  They should be vaccinated.   4% of these patients will have HBV DNA positive.
  • Patients who fail to respond to the vaccination, if obese use longer needle to immunize and inject in deltoid.
  • Liver injury occurs in immune escape and immune active.  They need treatment.
  • If adefovir resistance add lamuvdiine or switch to baraclude or viread
  • If baraclude resistance switch or add hepsera or viread

HCC

  • Best survival is liver transplant.  Second best is resection, third is local therapy.
  • 5thmost common cancer in the world and third leading cause of cancer death
  • HCC and not cirrhosis is the leading cause of death in chronic liver disease.
  • Incidence of HCC has tripled in 30 years.
  • Risk factors are cirrhosis (regardless of cause), HBV, HCV, male gender, iron overload, fatty liver, hypothyroidism is a risk factor of HCC in women?
  • Diagnosis can be made without biopsy. Hypervascular mass in cirrhosis is HCC till proven otherwise.
  • AASLD criteria – 2 cm mass on US vascular pattern is HCC or AFP more than 200 treat as HCC
  • AFP elevation is not needed to diagnose cancer.
  • Screen anyone with cirrhosis, hemorchromatosis pts, HBV carriers if : African age more than 20, family history of HCC, Asian male more than 40, Asian female more than 50 or anyone with HBV DNA more than 2000 or increased AT.  — USE US plus AFP or trochaic CT or MR every 6 months.
  • Milan criteria for transplant for HCC 1 lesion less than 5 cm or 3 lesions less than 3 cm.
  • Resection is for non cirrhotic liver if restricted to one lobe or univocal tumor.
  • If pt has elevated bilirubin or overt portal HTN 5 year survival is 25% with local resection.  If none of those, local resection has 70% 5 year survival.
  • TACE.  Risk includes higher MELD and portal vein thrombosis.
  • RFA
  • RFA plus TACE is better than either individual.
  • No role of ethanol ablation and limited use of cry ablation
  • Sorafenib for inoperable HCC.  It is an angiogenesis inhibitor.  Side effects include, diarrhea, bleeding, MI in 3% patients, perforation, HTN, voice change, fatigue, avoid sun exposure. Dose 400 bid.
  • Secondary prevention for HCC after transplant is birdlimes or sorafenib (STORM trial)

Cholangiocarcinoma

  • Ig G 4  cholangiopathy.  Treat with prednisone 40 mg  for one month and taper over 5 mg every 4 weeks.  Use level of more than 140 for Ig G 4.  Ig G 4 more than 280 is 90% specific.
  • Sarcoid cholangiopathy.
  • Ig G 4 elevation can occur in cholangiocarcinoma.
  • PSC life long risk of cholangiocarcinoma is 10%.
  • CA 19-9 elevation cut off used is 100 U/ml.  False positive if patient has bacterial cholangitis.
  • FISH (fluorescent in situ hybridization). Chromosome 3, 17, 7 and locus 9p21.  Use FISH if cytology is non diagnostic.
  • Eovist MRI
  • PET scan about 53% accuracy.  Positive predictive value is high 90% and neg predictive value is very low.
  • If FISH negative and CA 19-9 more than 100, treat as malignancy.  If FISH neg, CA 19-9 neg, get MRI plus MRCP and EUS.
  • You can survive with 30% of your liver.
  • It takes about 6 weeks after stent is placed,  for bilirubin to normalize if it was more than 10.  If less than 10, it takes 3 weeks to normalize.
  • Use neoadjuvant chemotherapy with liver transplant for treatment – gives best survival.

2012

Strategies for Hep B treatment

  • High viral load associated with higher chance of hepatoma.
  • Type C is associated with highest chance of hepatoma
  • Older the age higher the chance of hepatoma
  • ALT more than 45 – risk of hepatoma is higher
  • Cirrhosis also higher chance of hepatoma
  • New concept is HBsAg level than HBV DNA level correlates better with ccc DNA in liver.
  • Use HBsAG levels (<1000) and HBV DNA (<2000) gives best result of inactive carrier validation.
  • HBsAg loss after 2-5 years of treatment is less common (less than 5%.  One study showed 11%)
  • Traditionally we start treatment based on elevated ALT, inflammation on liver biopsy and presence of serum HBV DNA level.
  • AASLD guidelines suggests Rx when ALT > 2 x ULN and HBV DNA > 20,000 level.  Exception Lower threshold for pt > 4, active fibrosis and clinical evidence of cirrhosis. Then start treatment earlier.  Borderline ALT or HBV DNA do liver biopsy and monitor.
  • Resistance more likely in nucleosides or tides and no mutations in interferon treatment.
  • TDF and ETV should be initial Rx choice (entecavir or tenofovir).
  • Genotype A favor interferon treatment.
  • HBe Ag neg – Lack of HBsAG and HBV DNA decline at week 12 – futility rule for genotype D-HBV.  Hb e Ag+ pt, decline in HBs AG at week 12 and 24 predicts sustained response.
  • PEG treatment for 1 year.  May need longer for Hbe Ag neg.
  • Likelihood of HBeAg seroconversion 50% after 5 years treatment

NASH

  • 2 types Micro and Macro
  • NAFLD  – 30% of the US population has it
  • NASH occurs in up to 10% of US population
  • NAFLD increases risk of death – from liver, cardiovascular and cancer causes.
  • Fat in liver is an independent risk factor for CV death!
  • Nash with high activity score, DM, obesity and fibrosis have worse prognosis.
  • Caspase-3 generated fragments are seen in NASH.
  • CK-18 level in blood -? Diagnostic value for NASH
  • Rx for NASH – lifestyle changes
  • PIVENs study – vitamin E 800 IU/day was helpful and pioglitazone was not helpful
  • TONIC is other study which showed vitamin E helped. But weight loss is most important
  • Pioglitazone associated with risk of fracture and CV risk.
  • Rx of Vitamin E can increase risk of prostate cancer and 0.04% increase in risk of mortality from all causes.
  • ? role of gastric bypass.
  • Pentoxyfylline maybe helpful for NASH
  • PUFA on NASH – data is pending could be helpful.

HCC

  • AASLD slide recommendation
  • If mass is less than 1 cm, repeat US every 3 months. If it remains stable repeat every 6-12 months.  If it grows follow 1-2 cm recommendation
  • If more than 2 cm – dynamic CT or or MRI.  If typical for HCC – proceed with treatment for HCC WITHOUT bx.  Most transplant centers recommend proceed without bx
  • If between 1-2 cm, get CT and MRI. If concordant proceed accordingly.  If findings not concordant proceed with bx.
  • Staging based therapy – number, size, symptoms of HCC, cirrhosis presence and
  • If one lesion, less than 2 cm, and no cirrhosis, surgery is curative.
  • Look at slides in book.
  • RF ablation has 50% 5 year survival.