Hepatic dysfunction: Can we recognize it sooner? And intervene earlier

Transcription

1 Hepatic dysfunction: Can we recognize it sooner? And intervene earlier Juliet M.Lopez, M.D. Chief, General Surgery Division Raymond G Murphy Veterans Administration Medical Center, ABQ, NM Prometheus Hepatic Function Enzymes we most commonly look for Alkaline Phosphatase AST ALT Bilirubin, unconjugated or conjugated 1

2 Tests of liver function Serum bilirubin uptake,conjugation and excret Serum Alk Phos Cholestasis and biliary obstruct Serum GGT Cholestasis,biliary obst, ETOH Transaminases Hepatocyte necrosis Prothrombin time Protein Synthesis(I,II,V,VII,X) Albumin Protein Synthesis Aminopyrine breath test Microsomal Function Antipyrine clearance Microsomal Function Caffeine Clearance Microsomal Function Tests of Liver Function Lidocaine Clearance Microsomal Funct ( MEGX) Galactose elimination cap Cytosolic function ICG clearance (Indocyanine Green) Hepatic perfusion Sulfobromophthalein clear Tc-GSA scan Hepatic perfusion Functional Hepatocyte mass ICG clearance Some excellent studies performed that showed liver perfusion compromise was correlated to outcome in liver resected patients Conversely, multiple studies showed the lack of superiority of ICG clearance to the Child- Pugh score in cirrhotics, and predicting their outcomes. Fig A typical ICG clearance curve, which can be obtained by serial plasma sampling or optical pulse spectrophotometry. The arrow marks the ICG 15-minute retention value that is used most frequently to judge the adequacy of liver function. Copyright 2007 Elsevier Inc. All rights reserved. 2

3 Markers of Dysfunction include other organs as well Other markers of liver dysfunction: INR- international normalizing ratio Creatinine-kidney function/clearance Non-alcoholic Fatty Liver Disease (NAFLD) Fatty infiltration of the liver that does not include inflammation or liver fibrosis Can have this without any major liver failure just a fatty liver % Americans have this 2-5 % Americans have NASH basically NAFLD w/fibrosis 3

4 Non-Alcoholic Steatohepatitis(NASH) silent liver disease Liver biopsy necessary to diagnosis, otherwise just called NAFLD Becoming more and more common, likely because of increased obesity, and diabetes. Obesity over the last 10 yrs has doubled in adults and tripled in children!! NASH How do we diagnosis this? Elevated AST and ALT on routine labs R/o apparent reason for elevated liver enzymes first viral hepatitis excessive ETOH consumption medications taken NASH Usually silent for years with few or no symptoms Symptoms start, fatigue, wt loss, weakness Progression can take years, then cirrhosis present and nonreversible damage has occurred Leads to liver transplant (3 rd after Hep C and alcoholic liver disesase) 4

5 NASH Most patients are middle aged, and overweight or obese Elevated blood lipids such as cholesterol and triglycerides Many have diabetes NASH can occur without any apparent risk factor and can even occur in children It is NOT simply obesity that affects the liver! Treatment of NASH Most patients with NASH have insulin resistance Newer antidiabetic medications make people more insulin sensitive, and this may help with NASH Metformin Rosiglitazone Pioglitazone 5

6 NASH treatments Experimental research on antioxidants Vitamin E Selenium Betaine Model for End-Stage-Liver Disease (MELD) MELD is a scoring system that assesses the severity of chronic liver disease. Originally developed to predict death within 3 months of surgery in patients that had undergone TIPS procedure. Subsequently it was found to be useful in determining prognosis and prioritizing for receipt of a liver transplant. MELD how to calculate 3.78(ln serum bilirubin)+11.2(ln INR)+9.57(ln serum creatinine)+6.43 Bilirubin (mg/dl) INR- Creatinine ( mg/dl) 6

7 MELD mortality scale MELD 40 or more 71.3% mortality % mortality % mortality % mortality <9 1.9 % mortality Child-Pugh Score Designed years ago as a reference of liver disease and how that would correlate to mortality with operations Systemic shunts were performed in cirrhotic patients and mortality was calculated as such: Class A 0-8% mortality Class B 4-30% mortality Class C 10-70% mortality Child Pugh scoring is still used but appears to be unreliable in Class A patients. Child-Pugh Scoring System Points Ascites none small/diur tense Encephalopathy absent mild significant Albumin > <2.8 Bilirubin <2 2-3 >3 PT <4 4-6sec >6 INR < >2.3 Class A B C Points

8 Pharmocologic treatments of Cirrhosis Propranolol Somatostatin/Octreotide Nitric Oxide Endothelin History of Liver Disease Gastrointestinal symptoms Anorexia Nausea/vomiting Alteration of bowel function Pain/itching/jaundice Family hx/past medical hx Drug hx Foreign travel Etoh and smoking hx Clinical exam: Presence or absence of the stigmata of chronic liver disease Jaundice Spider nevi Hepatosplenomegaly Pruritis Caput medusae Ascites 8

9 Clinical features of hepatocellular failure Weakness Fatigue Wt loss Ascites Jaundice Hyperdynamic vasculature/ flushed extremities Peripheral cyanosis Fetor hepaticus(sweet musty odor of the breath) Cont. Clinical Features of Liver failure Gynecomastia Testicular atrophy mild confusion/shortened attention span Marked intellectual deterioration Turner s sign Cullen s sign 9

10 Cirrhosis and Portal Hypertension Pathologic aspects: Top 10 cause of death in the Western world Progressive deposition of fibrous tissue and vascular remodeling Fibrogenesis(triggered by liver injury) mediated by cellular necrosis,inflammation,apoptosis,and cytokines release. 10

11 Role of Liver Biopsy Liver biopsy evaluation remains as a primary diagnostic tool despite its level of invasiveness Establishing or confirming the diagnosis Assessing the possible cause Analyzing the grade of ongoing necroinflammatory activity Detecting dysplastic lesions or HCC Provides tissue for molecular, chemical, & biochemical studies Morphology According to the size of the nodules cirrhosis can be characterized as micronodular vs macronodular or mixed nodularity Mixed micronodular and macronodular is common in end stage liver disease regardless of the underlying etiology. 11

12 Acute Liver Failure Develops after a catastrophic insult to the liver and results in encephalopathy,usually cerebral edema in acute liver failure. Hyperacute liver failure- encephalopathy w/in 7days of the onset of jaundice Acute liver failure encephalopathy w/in 8-28 days of jaundice Subacute liver failure -enceph> 28 days of jaundice Viral Infection Hepatitis A infections occur 0.14% to 0.35% of hospitalized cases- in 0.4% in all cases seen in US Hepatitis B leads to 1-4% of cases hospitalized per year Hep C and D and E are much lower Drugs Acetaminophen-most common cause of acute liver failure in United Kingdom and US Usually overdose -attempts at suicide but 8-30% of cases follow therapeutic dosing Used in conjunction with antiepileptic medication and alcohol 12

13 Acetaminophen Overdose Poor prognostic indicators: Arterial Ph <7.25 after 24 hrs Serum lactate>3.5 Prothrombin time>100sec Creatinine >3.5 or anuria Grade 3-4 encephalopathy More Drugs Nonsteroidal antiinflammatories INH/Rifampicin Halothane Sulfonamides Flutamide Valproate Carbamazapine Ecstacy A.phylloides(mushrooms)-Europe and Calif coast! Statins Overall Strategy Management of acute liver failure N-aceylt cysteine is the antedote for acetaminophen overdose PCN, or silymarin is used for A. phylloides (mushroom) toxicity Pentoxifylline or corticosteroids are used for severe acute alcoholic liver failure 13

14 Portal HTN Portal HTN treatment Beta blockers, isosorbide mononitrate 35 to12% decrease in bleeds 18 to 10% reduction in fatal bleeds Compliance with medications Neurologic Complications Encephalopathy Grade 1,2,3 Drowsiness, disorientation, respond to verbal stimuli Short period of extreme agitation, then becomes confused, obeys simple commands Grade 4.deep coma, life threatening and disqualifies patient for a transplant Encephalopathy: precipitants and treatment Precipitants include Infection, Constipation, GI bleed, Increased Protein intake, Narcotics, Benzos Treatments include: Dietary Protein Restriction Lactulose Phosphate Enemas 14

15 Infection Major precipitant in chronic liver disease..even the most trivial of infections can trigger acute on chronic liver failure H/O SBP should be treated with prophylactic antibiotics Norfloxacin 400mg/QD Infection Most common cause of death in acute liver failure patients Frequently disqualifies patient from a liver transplant Bacterial 80% Fungal 20% Hemodynamics of Liver Failure Similar to SIRS or Sepsis Hyperdynamic at first then hypodynamic Circulatory collapse that then leads to Multisystem Organ Failure 15

16 Esophageal varix bleeds Octreotide Vasopressin Endoscopic variceal ligation is much better than endoscopic variceal sclerotherapy EVL mortality rates lower than sclerotherapy and Coagulopathy Thrombocytopenia present in 70% of patients with acute liver failure Decreased synthesis of all major coagulation proteins Prothrombin, fibrinogen,v,vii,ix,x Esophageal Varices Massive bleeding from pronounced veins in distal esophagus. Treatment..TIPS Transjugular Intrahepatic Portosystemic Shunt Less rebleeding, more encephalopathy and effective treatment of ascites.. 16

17 Portasystemic shunts vs medical management TIPS vs. Medical Management 17

18 Indications for TIPS #1 Continued variceal hemorrhage after banding or sclerotherapy #2 Prevention of rebleeding or tx of ascites while waiting for transplant #3 Prevention of bleeding in patients not a candidate for transplant Esophageal Varix Bleeding Old days-surgery, surgical shunt procedures rarely offered due to advent of TIPS Surgical devascularization procedures have extremely high mortality-esophageal transection or Sugiura procedure Liver transplant for patients of Child B or C TIPS as a bridge to transplant Must be abstinent from alcohol for 6 months Kidney Failure Acute on Chronic Liver Failure that leads to Kidney failure Type 1 Doubling of Creatinine or decreasing GFR by 50% in 2 weeks time Type 2 Hepatorenal syndrome not fulfilling above parameters Hepatorenal syndrome improves after transplant- but getting to that is the difficulty 18

19 Dialysis vs. Continuous Filtration Systems The metabolic complexity of liver and kidney failure at one time mandates a early intervention and is prudent in the setting of acute liver failure Dialysis no longer the mainstay- replaced by CVVH or MARS (molecular absorbents recirculation system) Decreased swings of volume status/fluid shifts, maintain better hemodynamics, and run a lower risk of aggravating cerebral edema 19