1. Severe alcoholic hepatitis can have better outcome (without going through requirement of abstinence for 6 months). Now transplant centers are accepting those patients for transplant.
2. Portal vein thrombosis in cirrhosis : Ok to anticoagulate. It is safe.
3. PVT increases cirrhosis mortality
4. Using anticoagulation improves LT outcome by renalization of PV
5. European data showed benefit of enoxaparin in PVT
6. Do EV banding prophylactically before using AC in PVT
7. Statins are safe in cirrhosis and internists are afraid to use it. That is a misconception.
8. Statin use shows improved mortality in cirrhosis.
9. Fibroscan and MRE are equal. Both are better than fibrosure. CPT is 91200. $ 134.80 for fibroscan.
10. kPa for F 2 is 4.5 and 7.65 and F 4 is 6 and 13 respectively for MRE and Fibroscan. This increases sensitivity but specificity is around 80%
EASL update, NAFLD and HCC
1. Remogliflozin for NAFLD NASH
2. NAFLD leads to HCC. Can occur without development of cirrhosis
3. Prevalence of HCC is HCV > NAFLD > ALD > HBV
4. HCC in NAFLD has shorter survival, older Caucasian patients, higher tumor stage
5. NAFLD two types : Isolated steatosis and NASH.
6. Liraglutide , vitamin E in pre cirrhosis. Victoza or Liraglutide trial (LEAN trial) (it is a GLP-1 analogue) Dose was 1.8 mg was dose SQ daily. It was 39% compared to placebo of 9% and prevented worsening compared to placebo. Consider using it after phase 3 trial.
7. Remogliflozin (selective SGLT2 inhibitor) Mice study. Effective in mice model, It is a safe and potent anti diabetic medicine and can be helpful for NASH
8. Emerging drugs for NASH : Obeticholic acid, GFT505 (PPAR agonist), aramchol (conjugate of bile acid and arachic acid)m antifibrotic agents like cenicriviroc, GR-MD-02, Simtuzumab
- ALI – acute liver injury. If HE then acute liver failure or ALF
- Gilbert – UDP – glucoronyltransferase defect, unconjugated bilirubin
- Hemolysis indirect bilirubin
- Drug reaction – sex steroids estrogens and testosterone inhibit transport and cause increased bilirubin
- Indinavir falaprevir inhibit UDPGT causes pseudo-Gilbert
- Irinotecan toxicity more likely in Gilbert
- Jaundice without enzyme elevation that occurs without sepsis. 30% jaundice precedes sepsis !! Liver histology of neutrophilic cholangitis predicts poor survival
- Jaundice maybe aggravated by hemolysis, hepatic congestion and renal failure are the cause of jaundice in sepsis
- HSV, HBV, Hepatitis A, B and C and HEV.(types 1 and 2 in the third world and types 3 and 4 in USA)
- HEV in deer, Pigs are the reservoir in USA.. Send PCR
- ALT/Alk Phos ratio – more than 5 is hepatocellular, cholestatis less than 2 and mixed if 3-4 ratio
- DILI – fever, eosinophilia, rash favors it
- Ischemic hepatitis – LV dysfunction and not right heart failure may not be apparent, hyptension, in CHF persistent aminotransferase elevation,jaundice is mild
- AIH – can be acute. ( can treat with with 20 mg prednisone, 50 not always needed) ANA positive, anti F-actin, Hypergammaglobulinemia, Ig G level DILI can cause AIH for eg, nitrofurantoin, minocycline and TNF – alpha antagonists. Impossible to differentiate DILI and AIH
- Early Acute biliary obstruction – AST and ALT goes up
- Severe ALI – ALI plus PT INR of more than 1.5 then severe ALI
- ALF – severe ALI plus HE
- ALF – Tylenol, indeterminate, DILI, AIH, ischemia HBV, HAV. Percents are 46, 12, 11, 7, 6, 7, 2. Survial without transplant 50%.
- Very high bilirubin and low ALT – Pregnancy related liver injury, Wilson
- Complications of ALI – cerebral edema, circulatory collapse, resp. failure, renal failure
- For management – bring Hb to 8 and SBP of 100. And ANTIBIOTICS to all pt with variceal bleed
- Vasopressin and NTG NO LONGER — — USED
- IGV 1 bleed – use BRTO or glue esp if cirrhosis. If IBV 1 from splenic vein thrombosis – splenectomy
- Portal HTN gastropathy – use beta blocker and or TIPS
- GAVE is in liver disease but without Portal HTN. Marsteller – Reuben syndrome is GAVE in nodular pattern in antrum and duodenum.
- HRS – type 2 therapeutic paracentesis frequently. Type 1 is MOSF. They have adrenal dysfunction – can consider 7.5 mg prednisone and improves survival !!!
- At mayo clinic PA did LVP even with INR as high as 8.7 and plt 19,000
- 2 gm sodium restriction. If urine sodium less than 127 – no fluid restriction needed
- 100 plus 40 then 200 and 80 lasix aldactone dose for ascites
- Pseudo refrectary ascites – on compliant patient. _ no processed meat, no salt on cooking or table, all fresh food is good and daily sodium is the same as year.
- Use IV albumin when treating SBP, prophylaxis of SBP – 250 mg of cipro (norfloxacin not available)
- Do not check ammonia level for HE for chronic liver disease
- Acute on chronic liver failure – sudden deterioration of liver disease. New term. Mortality is 33% at 30 days and 90 days 51%
- TIPS in 2014
- Covered stents caused pseudointimal hyperplasia
- Myth of INR
- Myths of elevated PT – FFP corrects PT and it prevents bleeding
- Fresh frozen is when plasma is frozen in 8 hours. Here in USA it is frozen in 24 hours.
- INR is NOT accurate in liver disease. INR was for Coumadin not liver disease
- Protein C def occurs in Childs C . Also low protein S and low anti – thrombin 3 but also high pro coagulant. Final answer – more of pro coagulation in liver patients with CTP C
- The procoagulant factors are NOT measured by PT.. So although PT and PTT is high it is compensated by pro coagulant factors / tendency in cirrhosis
- Von Willibrand factors rise in Childs A, B and C and even in ALF.
- High Von WIllibrand levels – leads and compensates for low platelets. Plt of less than 50,000 then bleeding problem.
- In essence there is re balanced hemostasis in Cirrhosis
- FFP 4 units corrects PT only in 10% of cases and after 6 units 20% corrected
- Higher chance of lung injury in patients who get FFP
- In essence FFP is the Interventionists Valium
- Adverse of FFP – anaphylaxis, allergy, TRALI, fever, (30% incidence of TRALI in cirrhosis) and TACO
- TEG and ROTEM – whole blood clotting – Thrombin elastography,
- 30 cc/kg is the dose needed to correct PT which has unacceptable risks. It is not needed.
- Reporting of DILI in Iceland, france is 14 to 19/100,000.
- Unknown for USA
- Antimicrobials and CNS agents.
- Commonest cause in USA is Augmentin
- ALF from INH, Bactrim and Nitrofuantoin
- More common in women
- Tylenol 70% will survive
- Serious DILI – If bilirubin is greater than2 and has hepatitis picture and refer to Univ center
- Seroprevalence of HEV – 20%
- Check HEV IgM from quest or HEV PCR at CDC
- CAMS (complimentary and alternative medicines) 9% of cases of DILI are from CAMS
- Carnitine for Depakote toxicity
- Prednisone for AIT from drugs
- Ursodexocycholic acid for cholestasis
- NAC for ALF with or without HE
- Hys law – if bilirubin > 3 and in hepatocellular injury has a 10% risk of death
- 14 % of dili progresses to chronic liver injury.
Renal dysfunction in cirrhosis
Simultaneous liver and renal transplant – Incidence is 7%
HRS type 1 doubling of Cr more than 2.5 in 2 weeks, no improvement after 1 g/kg/day, absence of shock
HRS 2 , Cr more than 1.5 mg/dl and no improvement with albumin
HRS i MELD more than 20 and median survival is 1 month
HRS 2 MELD is less than 20 and survival median is 6.7 months
Treat with stop all diuretics, rule out sepsis,admid to ICU, vasopressin or terlipressin, octreotide and milrinone alpha adrenergic
Terlipressin 1 mg IV every 6 hours, increase to 2 mg every 6 hours if no response. Discontinue at 14 days or if Cr drops to less than 1.5. Contrainications, CAD, arrythmias, severe asthma, COPD, pregnancy
Midodrine 2.5 mg every 8 hours and increase to 12.5 mg every 8 hours
Octreotide 100 mcg every 8 hours and increase to 200 every hours
MAP target is to increase by 15 mm Hg
Albumin 20-40 g/day
Other options are TIPS, dialysis and OLT
Related to nitric oxide dysfunction
Newer classification for HRS is – pre HRS, HRS 2, HRS type 1, Ischemic ATN and ischemic ATN with no recover Stage 1, 2, 3 and 4. Stage 2 is HRS 1 and 2.
Get urine to protein to Cr ratio.
If Cr goes up by 0.3 from baseline in 48 hours and or 0.5 ml/kg/hr for more than 6 hours consider acute kidney injury in cirrhosis
Cystatin C and Cr equations Stevens CKD-EPI equations 2012
Most accurate is CKD-Epi formula
Second is Stevens
Third is 6-variable MDRD
Fourth is CKD-epi cystatin C
Cirrhosis and ascites
Baclofen to reduce alcohol craving. 5 mg tid x 3 d then 10 mg tid for 5 days
Dietary sodium restriction 2 Good Morning (88 mmol/d)
Aldactone 100 mg a day and lasix 40 mg a day
Ur Na > K to lose weight. Double if Na/K < 1. Max dose is 400 and 160 seldom used. In that case, pt can be diuretic resistent
Low K, use aldactone alone
Only add lasix when K is normal. D/C diuretics for azotemia
In elderly use more lasix and less aldactone
BP and survival in cirrhosis – MAP > 82 70% survival. MAP les than 82, survival is 20%
If BP drops – midodrine oral alpha agonist, can increase BP nd improve response to diuretic
Propranolol causes harm in refractory ascites pt.
Vaptans – Satavaptan is not clinically beneficial and may increase mortality
Ascites – d/c inderal, ACE and ARB
LVP every 2 weeks – 8 liters general.
Pseudorefractory – from non compliance, sodium, on ice cream, soy sauce, NSAIDs, inderal, IV saline
Tap – use caldwell needle?
LVP does not cause “vacuum”
Edema in legs, the leg fluid goes into abd. in pt with rapid refilling of the abd
TIPS – Indications are diuretic resistant, multiple rapid re admissions, refractor hepatic hydrothorax, thin umbilical hernia, TIPS before it bursts
EF should be more than 60%, Check MELD, CPT less than 12,
Ascites is a contraindication to PEG.
EGV strategy – keep Hb between 7-9 rather than 9-11. Higher mortality in those whose Hb was 9-11 !Especially true for patients with CPT class A or b
Prophylactic antibiotics improve outcomes in cirrhosis with GI bleeding
Ceftriaxone is better than norfloxacin. 6/7 patients were resistant to Good Morning neg bacilli. However this was only 9% of the patients. So, if pt on norfloxacin, use ceftriaxone or advanced liver disease
Do EGD in 12 hours of bleeding after stabilizing
HVPG more than 20 are more likely to bleed
HVPG is higher in Childs C compared to child A (80% to 30%)
Child A patients have 0% mortality with GI bleed
So far child b and c, continues octreotide for 5 days
For childs C, consider TIPS in 24 hours
Replace self expanding metallic stent – has replaced blackmore sengstaken tube. Temporizing measure to TIPS
Start beta blocker before discharge.
GOV 1 treat like EGV
GOV2 and IGV1 is 15% of variceal bleed. – three Rx – TIPS, glue or BRTO ( balloon occluded retrograde transvenous obliteration )
BRTO only if pt has gastrorenal shunt.
TIPS contraindicated if pt has portal vein thrombosis
Management of complicated PORTAL HYPERTENSION
- Refractory Acites : Occurs in 10%. Two types. : Diuretic intractable ascites (cannot tolerate diuretics) 80%or diuretic resistant in 20% of casesLV paracentesis vs. TIPS. There is no survival benefit one over the other.
- Salt restrictions plus diuretics
- Use 6 to 8 gm of albumin with every liter fluid removed.
- LVP is preferred.
- TIPS if patient needs LVP every 7 to 14 days.
- TIPS Contraindicated in :, age more than 70, cardiac dysnfunction, encephalopathy, renal failure, Consider TIPS if MELD more than 20
- Hepatorenal syndrome. Two types. Type 1 : rapidly progressive (over days to weeks). Doubling of Cr, and halving of cr. Clearance to less than 20
- Type 2, slowly progressive, cr cl less than 40, cr. 1.5, and associated with refractory ascites.
- Hepatorenal syndrome. : No longer saline is considered as adequate for volume expansion. Use albumin 100 gm/day for volume expansion and urinary sodium is no longer a major criteria.. Absence of shock, cr more than 1.5, no concurrent nephrotoxic drugs and absence of renal disease.
- Use vasoconstrictors Terlipressin or octreotide + midodrine
- Use of terlipressin + albumin is best combination than just albumin. Indefinite duration of use of terlipressin.
- Side effects of terlipressin include can be serious.
- Use CVP pressure to assess intravascular volume in patients with HRS.
- HE : Hepatic encephalopathy. Three types A : acutle liver failure patients. B associated with portosystemic bypass without cirrhosis and type C in pateints with cirrhosis.
- Stages from confusion to drowsiness, somnolence to coma.
- Poor correlation of ammonia levels with presence or severity of HE.
- Minimal hepatic encephalopathy occurs in 30-70% patients. Detected with psychometric and neuropsychological testing, altered hand writing. Treatment is lacunose or symbiotic (probiotics and fermentable fiber)!
- Minimal HE is associated with imparied driving, defective visual constructive ability,, visual spacial perception impaired, attention deficits, altered handwriting
- HE is precipitated :by excess protein, GI bleeding, sedtaives TIPS, temp, diuretics, azotemia
- Protein restrction is NOT needed to treat HE
- Rifaximin for HE. Dose is 550 mg bid. Rifaximin was associated with 60% reduction of a subsequent HE. Decreases hospitalization by 50%.
- Unclear if lacunose works at all for HE
- Newwer guidelines : no protein restriction. Rifaximin will become firstline. Neomycin and flagyl of unproven value.
Refer for OLT
- MELD score varies from 6 to 40
- MELD more than 25 get a liver
- MELD between 15 to 24, encourage for living donor transplant
- MELD between 10-14 decreased QOL.
Update in Liver transplant
- Patients develop HTN immediately post transplant. Cirrhosis lowers the BP.
- DD for abnormal LFT post transplant
- Deceased donor Liver transplant : two ways duct to duct anastomosis or roux en y anastomosis.
- LDLT : here typically the right lobe of the liver is transplanted.
- Post op abnormal LFT : get an US with and without dopplers. Must check flow esp hepatic artery flow, Check immunosuppressive levels. Check for CMV. Check for HBV and HCV because of donor related viral infections. Patients may need liver bx, ERCP.
- Rejection usually shows endothelial injury on liver biopsy.
- Most of the rejection occurs in the first 90 days.
- Early sign is elevation of alk phos but soon it is ALT and AST elevation.
- Sirolium causes hepatic artery thrombosis, interstitial pneumonitis, elevated TG (All of these are black box warning)
- Drug interactions with transplant drugs : A must read : calcium channel blockers, antifungal and macrolides, reglan amiodarone tagamet cause elevated level of tacrolimus and cyclosporine.
- Biliary leaks usually in 30 days but can present months later!
- First month infections are donor related infections, bacterial infection and candida. In 1 to 6 months the infections are CMV, EBV, HIV, TB, cholnagitis, donor related
- Chronic renal disease – ESRD in 18% 5 years post op!
- Skin cancer, head and neck cancer is very common s/p OLT
Endoscopic Management of Portal HTN Bleeding
- Derma bond : off label use for GV.
- GAVE vs. Portal hypertensive naturopathy
- Transfuse to Hb of 8, use antibiotics and octreotide
- Banding every 2-4 weeks till eradiation
- EVL (band ligation ) 90% effective and better than sclerotherapy – less rebreeding, lower mortality, fewer complications,
- If actively bleeding varix found, band it there and DO NOT band distal to it.
- If no bleeding found, start from GE junction and move proximally.
- Distal 1/3 should be ligated 5-7 cm
- PPI should be used to help promote healing.
- Sclerotherapy is second line.
- Use sclerotherapy if band ligation cannot be done. Inject 1-2 cc at a time upto 20 cc at a session. More complications.
- GV. 10-15% of varcieal bleeding.
- Classifications is based on location GOV 1 and 2 (1 is on lesser curvature). GOV2 are fundic.
- IGV 1 are proximal body of stomach and IGV 2 is distal body..
- Treat GOV1 : Is an extension of Esophageal Varix and treat the same EV with banding or sclerotherapy.
- Fundal GOV 2 or IGV 1. Banding and sclera fail (90 to 100% rebleed rate). TIPS or glue is most effective.
- IGV stands for isolated gastric varices
- Cyanoacrylate : two types : Histoacryl (must be diluated with lipoidal) or derma bond. Dermabond is used for skin closure. Used undiluted. Risk of serious complications are 1-5 % include embolism, PE, CVA, severe infection and death at time of procedure.
- Avoid cyanoacrylate injection in intra pulmonary or intra cardiac shunts.
- No role for prophylactic glue injection.
- Technique. 3 cc for derma bond. Use Wilson cook 21 gauge Macron-haber. Use silicon at tip of scope. 1 cc over 15 seconds. If you inject too slow – needle gets glued to varix. If too fast – causes embolism.
- You can use endoclip to buy a few minutes while you get glue ready
- String assisted retroflexion.
- Once varix is glued repeat EGD in 4 weeks. DO NOT remove glue cast.
- Honeycombing of antrum is GAVE.
- GAVE is just restricted to antrum. GVE is diffuse and is in proximal and distal stomach.
- Mild PHG – mosaic, with minimal to no red spot, usually in proximal stomach and usually does not bleed.
- Severe PGH is mosaic with extensive red spots, causes bleeding and treat with beta blockers and TIPS
- PHG (portal hypertensive naturopathy) and limited endo therapy. More cobblestone than honeycombing.
- Multiple APC induced can lead to polyploidy lesions.
- Cryotherapy is emerging technique for GAVE / or GVE. Just spray . It requires multiple sessions. Use maximum 3 spraying per session.
- Band ligation or cry therapy for GVE if refractory to APC. Use banding for APC induced bleeding polyposis.
Assessing patients who have cirrhosis who need surgery.
- Problems of cirrhosis on surgery include decreased liver blood flow, bleeding, increased incidence of aspiration pneumonia, pneumoperitoneum, hypoxemia and medications that are metabolized by liver.
- Pre op tests needed include MELD, Child-Pugh scores. Check plt and INR.
- Consider stress test in patients with NASH or NAFLD. Higher incidence of cardiovascular disease in those patients.
- Contraindications for elective surgery would be acute liver failure, acute viral hepatitis, hypoxemia, severe coagulopathy, alcoholic hepatitis.
- Child A mortality is 10 and 22 %, for B it is 30 to 38% and C it is 80% to 100% (for elective and emergency surgery)
- MELD more than 8 – high incidence of complications post cholecystectomy. 1% per MELD score in increased 30 day mortality if less than 20. If MELD more than 20, 2% per score increase in mortality.
- MELD is more than 14 it is superior to Childs C for predicting death / need for liver transplant.
- MELD score look up online : www.mayoclinic.com/meld/mayomodel9.htm
- Use both Chilts (CTP) and MELD. Inform pt and surgeon.
- Correct coagulopathy with Vitamin K 10 sq for 3 days, give FFP, plt, cryoprecipitate and recombinant Oral is not effective. factor VIIa. Minimize use of preop diuretics, paracentesis.
- For AIH use stress dose of steroids.
- Check albumin – consider enteral support.
- Extubate as soon as possible, minimize sedation, IV albumin as fluid replacement.
Nutrition in ESLD
- PEM is common. This is due to insulin resistence, anorexia, dietary restrictions, leptin levels, increased cytokines, dietary restrictions, nutrient malabsorbption, medications