Management of Liver Failure and Cirrhosis Hesham Elgouhari, MD, FACP Associate Professor of Medicine Hepatologist and Medical Director, Avera Center for Liver Disease.
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Management of Liver Failure and Cirrhosis Hesham Elgouhari, MD, FACP Associate Professor of Medicine Hepatologist and Medical Director, Avera Center for Liver Disease Management of Cirrhosis: How are we doing? Large body of high-quality evidence Many randomized trials and guidelines Despite all of that, Not doing very well: • • • • • Cirrhotics received Hepatitis A/ B vaccines: 7%-62% EV/GV grade II-III on NSBB: 6%-22% Cirrhotic ascites on recommended therapy: 33% HCC surveillance: 16%-28% One month readmission of cirrhotics: > 30% Improving Cirrhosis Care The Need for Coordination Generalist and subspecialist Bini et al: GI/Hepatology consultation was associated with improved outcome for patients hospitalized with decompensated cirrhosis Limited access Fragmentation between inpatients& outpatient settings and between PCPs& Subspecialists Limited application of Multidisciplinary team approach Team Work… Practical Approach of Cirrhosis Management Characters of inpatient cirrhotics Very sick Crash easily and quickly Multiorgan dysfunction Multidisciplinary management Atypical presentations of common acute illnesses (Infections and kidney diseases) Malnourished Characters of inpatient cirrhotics Medications are sometimes very dangerous Surgeons Elective procedures Discharge plan Only one Backup: Liver Transplantation which is complicated and not easily available Five Questions Does the patient have cirrhosis? What is (are) the cause(s)? What stage of Cirrhosis is present? What is (are) the complication(s) present? What is the status of Liver Transplantation? Question # 1: Does the patient have cirrhosis? Terminology in Hepatology What are you dealing with? Transaminitis Hepatitis Liver Failure Liver fibrosis Liver cirrhosis Acute Liver Disease Chronic Liver Disease Acute on top of Chronic Liver Disease ESLD Cirrhosis, Relevant Facts The word cirrhosis comes from the Greek word “kirrhos”, the name for a yellowish-brown color The definition of cirrhosis remains pathological, described by “WHO” in 1978 as: “a diffuse process characterized by fibrosis and the conversion of normal liver architectures into structurally abnormal nodules” Cirrhosis, Relevant Facts The prevalence is not well known About two Million outpatients visits and 750,000 hospitalizations per year for CLD About 40,000 per year progress to ESLD, Liver failure and death Cirrhosis, Relevant Facts The 12th most common cause of death in USA In 2007, more than 29,000 patients died from it In August 2010, About 16,000 were listed for Liver transplant, only about 6000 got it About 5%-10% listed for LT died while waiting Natural history of chronic liver disease Increasing liver fibrosis Jaundice Encephalopathy Variceal bleeding Ascites 5%-7%/Y Chronic Liver Disease Compensated Cirrhosis Decompensated Cirrhosis Death 2%- 7%/Y -Steatohepatitis -HBV& HCV Hepatitis -Autoimmune Hepatitis -Biliary liver disease -Metabolic/Hereditary Liver Disease -Others HCC Death Liver Transplantation When should you look for Liver disease? Positive RISK FACTOR and/or Positive “Others” Unlike heart or lung or even Kidney… All “others” ALONE are NOT 100% sensitive What are the “others”? • • • • History and Physical Liver chemistry tests Abdominal imaging EGD findings: Varices or PHG Liver Cirrhosis… When should we think of it History: • • • • Positive for a cause of CLD as HCV, ETOH,... Symptoms of hepatic decompensation Remember it in diabetic and/or obese patients Up to 40 % of cirrhotic patients are asymptomatic Liver Cirrhosis, When should we think of it Physical examination: • • • • • • General appearance Temporal wasting Skin signs Ascites/leg edema Splenomegaly (It is OK…) Asterixis in patients with AMS Liver Cirrhosis, When should we think of it Lab: • • • • Low plat. Count! It is not ITP yet… AST:ALT > 1 in non alcoholic CLD Hyperbilirubinemia Hypoalbuminemia Abnormal Abdominal Imaging Hepatomegaly Splenomegaly Fatty liver (coarse echogenicity): ALD& NAFLD Lobulated liver margin, shrunken Liver, or nodular Liver, large left lobe with small /low normal right one Cirrhosis Varices Ascites Liver Biopsy Question # 2: What is (are) the cause(s)? What is the cause Alcoholic Liver Disease (ALD) Non Alcoholic Fatty Liver Disease (NAFLD) Chronic Hepatitis C Chronic Hepatitis B AIH Hemochromatosis PBC/PSC Wilson disease Alpha one Antitrypsin Deficiency Diagnosis of ALD The Diagnosis is based on: History of significant ETOH intake Clinical evidence of liver disease Supporting Laboratory abnormalities Not that easy Have a low threshold to suspect ALD, but in a gentle way Four tools: History (Questionnaires) Physical Examination Laboratory studies Liver Biopsy What is our performance? McQuade et al*: 300 random patients were interviewed Use Questionnaires to assess DSM-IV for diagnosis Compare to physicians’ diagnosis *McQuade WH et al. Detecting symptoms of alcohol abuse in primary care settings. Arch Fam Med 2000 Sep;9(9):814-821 Risk factors for NAFLD A common disease Linked to Metabolic Syndrome& IR Could show up with manifestations of decompensated cirrhosis In diabetics, NAFLD is present in 63% In morbidly obese patients undergoing bariatric surgery, NAFLD is present in 96% The features of the MS are commonly seen in subjects with NAFLD METABOLIC SYNDROME Feature Obesity Diabetes Hypertension Dyslipidemia Prevalence 50-90% 20-50% 25-70% 35-75% Still, Patients without any component of MS but with Insulin Resistance can have NAFLD The Suggested Natural History of NAFLD Majority Simple Steatosis Stable Liver cancer ? ? NASH 10%/7 yrs 25%-35% 65%-75% Stable or with Regression Fibrosis 9%-20% Cirrhosis Progression 50%/7 yrs Liver failure 22%-33% Death or OLT NAFLD Rapidly growing cause of CLD/Cirrhosis Expected to be the most common cause of liver failure and liver cancer (HCC) Add “Liver” to your diabetic patients check list beside heart, kidney, eye,…. NASH could be presented with biopsy proven cirrhosis even with normal LFTs NASH could be presented with liver failure/HCC HCV Risk factors: Screen regardless LCT BABY BOOMERS (DOB between 1945-1965) IVDU: In the recent or remote past even once Hemophiliacs who received clotting factor concentrates before 1987 Blood transfusion/ organ transplant before July 1992 Patients on HD HIV patients Children born to HCV-infected mothers Sexual partners of HCV-infected patients Elevated liver enzymes Others: Occupational exposure, Tattoo, Cocaine abuse HBV Risk Factors: Screen regardless LCT Immigrants and adopted children Households of HBs Ag positive patients Sexual contacts of HBs Ag positive patients Persons who have ever injected drug Persons with multiple sexual partners or Hx of STD Before Immunosuppressive therapy Men who have sex with men Inmates of correctional facilities Individuals with chronically elevated ALT or AST Individuals infected with HCV or HIV Patients undergoing renal dialysis All pregnant women Risk Factors for Autoimmune Liver Disease Other Autoimmune Diseases: • About 35%-60% of patients with AIH • RA, SLE, HT, DM-2, … IBD: • Among IBD patients (UC>CD), 4% have PSC • Among PSC patients, 2/3 have IBD Family history of PBC Hereditary Liver Disease All are AR Hereditary Hemochromatosis: • Relatively common (1:300) • Get Iron studies in patients with abnormal LCT Alpha one Antitrypsin deficiency Wilson Disease If you have an index case Screen first degree relatives Treatment of the cause Very helpful Achieves variable degrees of reversibility CHC, CHB, ETOH, and AIH are the prominent examples in compensated cirrhosis CHB and ETOH are the prominent examples in decompensated cirrhosis Risk: Benefit Ratio Question # 3: What stage of Cirrhosis is present? Natural history of chronic liver disease Increasing liver fibrosis Jaundice Encephalopathy Variceal bleeding Ascites 5%-7%/Y Chronic Liver Disease Compensated Cirrhosis Decompensated Cirrhosis Death 2%- 7%/Y -Steatohepatitis -HBV& HCV Hepatitis -Autoimmune Hepatitis -Biliary liver disease -Metabolic/Hereditary Liver Disease -Others HCC Death Liver Transplantation Child-Turcotte-Pugh Score Model for End stage Liver Disease (MELD) Designed first to assess Candidacy for TIPS Shown to be very good (Not perfect) in predicting short term mortality Based on Creatinine, T. Bilirubin, and INR Objective and immune to behavioral biases MELD exception (HCC, HPS, others) The initial concern of ‘Sickest first” system would decrease post LT survival faded MELD < 15 carries more risks with surgery MELD Modifications MESO index: MLED and S. Sodium • Mortality of patients with low MELD +Na <125 = that of those with MELD of 20 points higher iMELD: Age, S. Sodium, and MELD The United Kingdom End Stage Liver Disease Score (UKELD) Liver INR MELD-XI (patients on AC therapy) MELD Modified-by-Gender score Cirrhosis Stages Characters Stage I Stage II No varices or ascites Non-bleeding Varices 1-Year mortality 1% 3% Stage III Ascites 20% Stage IV Variceal bleeding +/Ascites 57% Question # 4: What is (are) the complication(s) present? Complications of Cirrhosis Portal Hypertension • • • • • Ascites Esophageal and Gastric Varices Hepatorenal Syndrome Pulmonary Complications (HH, HPS, PPHTN) Hypersplenism Coagulopathy Encephalopathy ? Cardiomyopathy Hepatocellular Carcinoma Malnutrition Ascites The most common complication of cirrhosis About 50% of patients with compensated cirrhosis will develop ascites over a 10-year period After 2 years of ascites, the mortality rate is 50% With refractory ascites, one-year survival is 57% Be careful about the kidneys! Ascites The most common cause of ascites in the US is cirrhosis (about 85%), then heart disease, cancer& TB The old theory is the “Backward” theory with cirrhosisPHTNBackward Pressure in the splanchenic capillariesFluid leak from the capillaries The new theory is “Forward” theory in which splanchnic art. vasodilatation (SAVD) is the key word: • Forward increase in the capillary pressure in the liver with subsequent increase in lymph formation > lymph absorption • Arterial underfilling in the systemic circulation (blood stagnation in the spalnchnic area) ++ of hypovolemic hormones (RAAS), SNS, and ADH Approach to Ascites...Easy! Do Paracentesis Get Cell count with diff always to rule out SBP Get ascitic albumin and protein Get Serum Ascitic Albumin Gradient (SAAG) If ≥ 1.1 Portal Hypertension: • If Protein > 2.5Think more of cardiac ascites • If protein < 2.5gm/dlThink more of cirrhotic ascites If <1.1 Others (Cancer, TB, Renal, Thyroid…) Ascites Management Salt not fluid restriction NO NSAIDs Diuretics especially Spironolactone and maximize with monitoring Paracentesis: • Always for any inpatient if feasible • Get Cell count in a purple-top tube • No limit but give Albumin if ≥ 5 Liters or even less with renal insufficiency Transjugular Intrahepatic Portosystemic Shunt (TIPS) Spontaneous Bacterial Peritonitis No specific or sensitive symptom or sign Ascitic fluid analysis is the only way PMNLs > 250 cells/cc and/or Positive Culture Ascitic fluid culture in BC tubes (80% Vs 50%) The usual MOs are E. coli (43%), Klebsiella (11%), Pneumococci (9%), and others Treat with 3rd GCS and add Albumin if TB > 4, Creatinine > 1, or BUN > 30 ↓ HRS & short term Mortality Indefinite secondary prophylaxis if ascites exists EV, GV, and PHG Any patient with cirrhosis should get EGD: • Present in 30% of patients compensated cirrhosis • Present in 60% of patients with decompensated cirrhosis Risk of Bleeding increases with large varices, CPS of B or C, and red wheel sign Use Nonselective BB or EVL for 1ry prophylaxis In a large meta-analysis, the risk of the first variceal bleeding was 14% in those on BB compared to 30% in those on placebo BB acts by: • ↓ COP (via β1 receptor) • Inducing splanchnic vasoconstriction (via β2 receptor) ↓ splanchnic blood flow ↓ Portal flow and PV pressure. Variceal Bleeding Despite every thing we have, the current mortality of EV bleeding is at least 20% at 6 weeks and the immediate mortality from uncontrolled bleeding is 50% Variceal bleeding ceases spontaneously in 40-50% of cases& in 80% by active therapy if done in the 1st 24h With acute variceal bleeding: • ICU + Air way protection + good IV lineSSS with IVF • Octreotide IV (50 ug loading dose then 50 ug/hour for 3-5 d) • Keep Hb around 8 gm/dL and do not replace all lost blood (increase rebleeding risk and the mortality if you give more) • Ceftriaxone 1 gm IV daily for ≤ 7 days • EGD within 12 hours • Platelet and/or FFP transfusion if needed • Alert IR for possible TIPS Hepatic Encephalopathy (HE) HE-A for ALF-related; B for Bypass (shunt) without intrinsic liver disease; and C for cirrhosis-related HE Regarding B and C: • Minimal HE: with 2 or more abnormal psychomotor tests (Digit symbol test, Block design test, Number connection test A and B) • Episodic HE: Spontaneous, precipitated, or recurrent (2 or more within 1 year) • Persistent HE (> 28 days): Mild (grade I and II), Severe (grade III and IV), and treatment-dependent HE, Lines of Management Make sure of Diagnosis (No alternatives or Concomitant problems) Look for and treat the Predisposing Factors Specific Therapy Make sure of Diagnosis Cirrhotic patients are not immune to other causes of AMS Gradual Onset Presence of precipitating factors Asterixis Non focal Neuro exam Ammonia level is not helpful Get CT head in the following scenarios: • • • • Severe HE (grade III or IV) Focal Neurological examination Head trauma is suspected or confirmed Absence of recovery/improvement with standard treatment Predisposing Factors Increased NH3 level (↑ production or ↓consumption): • • • • GIB, constipation, and high protein diet ↑ NH3 production Portosystemic shunt Decreased hepatic consumption HypoKIncreased NH3 production by the kidney Azotemia and Dehydration (overuse lactulose with hyperNa) Decreased NH3 renal excretion • Diureticsdehyration, azotemia, and sometimes, hypoK Increased sensitivity of CNS to toxins: • Metabolic alkalosis increased BBB permeability to NH3 • Psychoactive medications • Hponatremia cerebral edema Increased hepatic dysfunction: • Acute AH • Surgery with hepatic hypoperfusion Infections: By all of the above 3 mechanisms Specific Therapy Lactulose//Krystalose: • Still first line and cheap • Has side effects as Diarrhea that may ↑ Serum Na and Ileus • Get 3-4 semisolid BM daily Rifaximin: • Has less side effects • Decreases breakthrough by 58%& HE-related hospitalization by 50% Neomycin: • Rarely used now • 4% get absorbed may lead to renal or Oto toxicity Flagyl: • Do not give it for long dutration as it may lead to neuropathy Others: • Do not restrict protein intake completely • Compliance HRS A clinical syndrome of renal and cardiovascular disturbance that occurs usually in patients with advanced cirrhosis with portal HTN HRS-I (Progressive) and HRS-II (Less progressive) Cirrhosis Portal HTN ↑ NO Splanchnic VD ++ Vasoconstrictor system (RAS and Sympathetic NS) VC of cerebral, UE, LE and renal BV the latter leads to ↓ RBF↓GFR with normal tubular function at least initially The PFs are Infections (SBP), LVP without albumin, and Acute AH The median Survival for patients with HRS-I is 1 month and 7 months for those with HRS-II Diagnosis of HRS: 4 Elements Cirrhosis Ascites Creatinine > 1.5 mg/dL No other cause of AKI like: 1-Sepsis with onset before not after AKI (usually not that clear in practice) 2-Volume depletion (not better with Albumin and being off diuretics for at least 2 days 3-No Nephrotoxic drugs for the last 2 weeks • 4-No parenchymal renal disease as suspected by: -Proteinuria > 500 mg/day -Microscopic hematuria (< 50 RBCs/HPF) -Abnormal kidney imaging Management of HRS Avoid Nephrotoxic drugs and diuretics Liver Transplantation Evaluation HRS-I: • • • • Albumin Vasoconstrictors (Octreotide& Midodrine) Terlipressin/Noradrenaline RRT if OLT candidate HRS-II • LVP with Albumin • ? TIPS • ? Vasoconstrictors (Octreotide& Midodrine) Cirrhotics and Infections Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis Overall median mortality of infected patients was 30.3%, 44% and 63% at 1-, 3- and 12 months, respectively. The main factor independently associated with death was the occurrence of renal failure Age, severity of cirrhosis, shock, HE and nosocomial infections were other independent predictors. Obtaining BC in cirrhotics is almost always needed Empiric Antibiotic use is often needed Cirrhotics and Nutrition Protein-calorie malnutrition (PCM) in cirrhotics is multifactorial PCM is progressive and parallels the severity of liver insufficiency: • 20% of Child’s Class A patients • 65%–90% of patients with more advanced liver disease • Nearly 100% of liver transplant candidates frequent meals, daily weights, and nutrition consultation on all hospitalized patients Protein intake 1.2-1.5 grams/Kg/Day Question # 5 What is the status of Liver Transplantation? A Mandatory Question… Too early…Rare Not interested….Uncommon With a clear obvious contraindication Under evaluation Not a candidate Actively Listed On Hold Thank you….