ABIM Review Hepatology

Transcription

1 ABIM Review Hepatology Norah Terrault, MD, MPH Associate Professor University of California San Francisco July 15, 2009 Liver Review Diagnostic algorithms for cholestatic versus hepatitic pattern of liver test abnormalities Viral hepatitis: acute and chronic Autoimmune and cholestatic liver diseases Fatty liver disease Alcoholic liver disease Cirrhosis and its complications Ascites, Encephalopathy, Variceal bleeding Liver transplantation - indications and contraindications

2 Case #1 30 yr female with pruritus and fatigue X 3 months. Only PMH: mild ulcerative colitis, stable. No meds P/E: Scleral icteric, multiple spider angiomata, palmer erythema. Abdomen hepatomegaly. Laboratory tests: Normal CBC, INR, albumin AST 39 (N<40) ALT 51 (N 50) Alkaline phosphatase 890 (N<120) Total bilirubin 3.2 (N 1.3) Ultrasound abdomen: Hepatomegaly Mild dilatation of distal left intrahepatic duct and proximal right intrahepatic ducts Normal common bile duct, gallbladder and spleen Q1 Which of the following is the best test to establish the patient s diagnosis? A. Blood tests: antimitochondrial antibody, antinuclear antibody, IgG and IgM B. Blood tests: anti-hcv, HBsAg, anti-hav IgM C. Liver biopsy D. Cholangiogram (ERCP or MRCP) E. CT scan with pancreatic protocol

3 Q1 Which of the following is the best test to establish the patient s diagnosis? A. Blood tests: antimitochondrial antibody, antinuclear antibody, IgG and IgM B. Blood tests: anti-hcv, HBsAg, anti-hav IgM C. Liver biopsy D. Cholangiogram (ERCP or MRCP) E. CT scan with pancreatic protocol Cholestatic Liver Enzyme Pattern (Elevated alkaline phosphatase ± bilirubin) Sources of elevated alkaline phosphatase are almost always LIVER or BONE Note: In pregnancy, placental alkaline phosphatase increases ~2 X ULN starting month 3 of pregnancy Work-Up Establish hepatic origin GGT or 5 nucleotidase or fractionation of alkaline phosphatase if bilirubin in normal Primary differential is intrahepatic versus extrahepatic disease Abdominal imaging is usual first test

4 Diagnostic Approach for Patient with Cholestatic Enzyme Profile US Abdomen Abnormal Biliary Tree Normal Biliary Tree Stones, Tumors Strictures Cholangiography Primary biliary cirrhosis Drugs/toxins Infiltrative Dz e.g Lymphoma Granulomatous Dz e.g. Mycobacterium, sarcoidosis AMA, IgM (PBC) Liver biopsy Cholestatic Liver Diseases Elevated Alkaline phosphatase ± bilirubin Diagnosis Primary sclerosing cholangitis Primary bilary cirrhosis Drug-toxicity Sarcoidosis Malignancy: lymphoma Infectious Clinical Clues Presence of ulcerative colitis Autoimmune diseases, female History of exposure Lung, lymph node, other systems involvement Hepatosplenomegaly, adenopathy B symptoms Fever, abnormal abdominal imaging First Order Testing Cholangiogram, usually MRCP AMA+, IgM elevated Withdrawal Biopsy: non-caseating granulomas; ACE level Biopsy Cultures other sites, liver biopsy

5 Idiopathic Chronic Cholestatic Liver Diseases Primary Sclerosing Cholangitis(PSC) Symptoms: fatigue, pruritus, weight loss, fatsoluble vitamin deficiencies, cholangitis 70% has ulcerative colitis Dx: cholangiogram is test of choice Intrahepatic ducts involvement ± extrahepatic duct disease panca+ common (but insufficient to establish dx) Biopsy suggestive but not usually diagnostic Treatment: None established Liver transplantation if decompensated liver disease Increased risk of cholangiocarcinoma Idiopathic Chronic Cholestatic Liver Diseases Primary Biliary Cirrhosis (PBC) Clinical presentation: Pruritus, fatigue, fat soluble vitamin deficiencies Assoc. with other autoimmune diseases 90% women! - usually present middle-age Signs: jaundice, xanthelasma, excoriations Diagnosis --> Antimitochondrial Ab (AMA>1:160): present in 95% of patients with PBC IgM elevated, other autoantibodies may be positive Liver biopsy to confirm diagnosis and stage disease Treatment: Ursodeoxycholic acid Improves enzymes, symptoms and prolongs transplant-free survival

6 Case #2 A 42 year old male with 10 day history of fatigue, mild nausea, anorexia and dark urine No significant PMH Social History: Heterosexual partner, no children. Moderate alcohol and marijuana use, no injection drug use Exam: icteric, few cervical nodes, mild RUQ tenderness, no splenomegaly, no asterixis Labs: WBC 3,200 (50 PMN, 32L, 5M, 4E), normal H/H, plts ALT 1804 U/L, AST 1500 U/L, total bilirubin 9.5 mg/dl, ALKP 241, INR 1.1, creat WNL Initial work-up: Case #2 Anti-HAV IgM positive Anti-HCV negative HBsAg negative, anti-hbc positive, anti-hbs positive ANA 1:80 Drug/alcohol screen: positive for cannabinoids and alcohol Ultrasound: patent portal vein and hepatic veins, heterogenous liver of normal size, no splenomegaly or ascites

7 Q2 Which of the following is indicated? A. Vaccinate coworkers B. Vaccinate partner and household members C. Refer to transplant center D. Admit for administration of N-acetyl cysteine E. Start antiviral therapy for hepatitis B Q2 Which of the following is indicated? A. Vaccinate coworkers B. Vaccinate partner and household members C. Refer to transplant center D. Admit for administration of N-acetyl cysteine E. Start antiviral therapy for hepatitis B

8 Hepatitis Pattern of Liver Enzymes Elevation ALT and AST elevated Distinguishing acute versus chronic hepatitis Symptoms: Acute: anorexia, nausea, RUQ discomfort, fatigue, flue-like symptoms Chronic: usually asymptomatic, fatigue Prior history Acute: no prior history of abnormal liver tests Severity of ALT elevation Acute: ALT >500 IU/L Chronic: Usually 250 IU/L Acute Hepatitis Diagnostic Work-Up Differential diagnosis Drugs/toxins (acetaminophen most common) Acute viral hepatitis - A, B, C, D, E. herpes, others Ischemia (shock liver) or hepatic congestion (Budd Chiari syndrome) Other: acute fatty liver of pregnancy autoimmune hepatitis (occasionally) Wilson s disease Work-up Drug/alcohol screen HAV IgM, HBsAg, anti- HBcIgM, anti-hcv, Monospot, other viral Abdominal US to assess hepatic veins ANA, IgG, ceruloplasmin

9 Acute Hepatitis Management Supportive care Admit for management of acute hepatitis symptoms: nausea, abdominal pain, etc Liver transplantation a consideration if: Develops hepatic encephalopathy or Increasing INR or bilirubin Specific antidotes for drugs N-acetyl cysteine for acetaminophen toxicity Penicillin G or Silibinin for Amanita mushroom poisoning Steroids if autoimmune hepatitis Copper chelating agents if Wilson s disease Antivirals in select cases of hepatitis B Prevention of HAV General Hygiene (e.g., hand washing) Sanitation (e.g., clean water sources) Specific Hepatitis A vaccination (pre-exposure) Immune globulin (preand post-exposure) Pre-exposure --> travelers to intermediate and high HAVendemic regions Post-exposure - within 14d to household and sexual contacts Recommendations For Adult HAV Vaccination Men who have sex with men Injection and non-injection drug users International travelers People with clotting factor disorders Patients with chronic liver disease Individuals working with HAV in laboratory setting MMWR 2006;55(RR-7)

10 Case #3 47 yr-old female referred for abnormal liver tests X 6 mos. Asymptomatic. PMH: Hypertension on Atenolol, diet-controlled DM and hypertriglyceridemia. No other meds. Denies alcohol use. No prior blood transfusion, injection drug use. P/E: Body mass index (BMI)=35. Abdomen: liver edge palpable, no splenomegaly LABS: AST 65 (N<40), ALT 75 (N<45) Alkaline phosphatase total bilirubin, albumin, prothrombin time and CBC normal Case #3 Additional Testing Performed Anti-HBc+, HBsAg neg, anti-hbs negative Anti-HCV negative ANA positive 1:80 Antimitochondrial antibody negative IgG and IgM normal Ferritin and transferrin saturation normal Ceruloplasmin normal Ultrasound: diffusely hyperechoic liver, otherwise normal, hepatic vessels patent

11 Q3 The most likely diagnosis is: A. Chronic hepatitis B B. Non-alcoholic fatty liver disease C. Drug-induced hepatotoxicity D. Autoimmune hepatitis E. Hepatocellular carcinoma Q3 The most likely diagnosis is: A. Chronic hepatitis B B. Non-alcoholic fatty liver disease C. Drug-induced hepatotoxicity D. Autoimmune hepatitis E. Hepatocellular carcinoma

12 Chronic Hepatitis Pattern Elevated ALT (and AST) Sporadic, isolated ALT elevations need no further w/u Persistent ( 6 mos) ALT elevation = chronic liver disease For most chronic liver diseases, ALT <300 U/L ALT slightly > AST or approximately same If AST>ALT = consider alcohol (usx. 2:1 ratio) DDx: Hepatitic Liver Enzyme Pattern Diagnosis NAFLD HBV HCV Autoimmune Hepatitis Alcohol, drugtoxicity Hemochromatosis Wilson s dz Clinical Clues Metabolic syndrome Risk factors: sex, injection drug use, + family hx Risk factors: Injection drug use, blood transfusion, occupational Female, other autoimmune conditions pseudogout, DM, heart dz, + family history <40 yrs, neuro or Psy sx, hemolytic anemia, pseudogout History of exposure First Order Testing Abdominal imaging to look for fatty liver HBsAg, anti-hbc Anti-HCV ANA>1:160, antismooth muscle Ab >1:40 Transferrin saturation >45%, ferritin >200 Low ceruloplasmin, high Urine copper (24 h) Abstinence or removal

13 Case #3 Clues in Evaluating AST/ALT AST 65 (N<40), ALT 75 (N<45) PH: Hypertension on atenolol, and diet-controlled DM, hypertriglyceridemia. No other meds; denies use of herbs. Denies alcohol use. Asymptomatic. P/E: BMI=35, no stigmata chronic liver disease. Abdomen obese, liver edge 2 cm below costal margin, spleen not palpable. Testing to exclude other causes all negative: anti-hbc+, HBsAg neg, anti-hbs neg = HBV immune ANA positive 1:40 = not autoimmune dz (titer too low) Ultrasound: diffusely hyperechoic liver, otherwise normal NAFLD: Non-Alcoholic Fatty Liver Most common causes of chronic liver disease in U.S. Histology like alcohol but diagnosis requires absence of significant alcohol Alcohol 2 drinks per day Variable severity evident on liver biopsy Simple steatosis (fat in hepatocytes) --> steatohepatitis (fat plus inflammation) --> steatohepatitis plus fibrosis --> cirrhosis Steatosis alone NOT at risk for cirrhosis Associated with the metabolic syndrome Centrally-distributed obesity (waist circumference) Elevated triglycerides ( 150 mg/dl) Hypertension (BP 130/85) Diabetes (or insulin resistance*)

14 Causes of Non-Alcoholic Fatty Liver Disease Primary Metabolic syndrome Secondary Much less frequent cause but to be considered Nutritional Protein calorie malnutrition TPN, Rapid weight loss JI bypass surgery Metabolic/Genetic Lipodystrophy Abetalipoproteinemia, Weber-Christian Disease Drugs Glucocorticoids, Estrogens, Antiretrovirals Calcium channel blockers, Valproic acid, Amiodarone, Tetracycline,Methotrexate, Others Small bowel bacterial overgrowth HIV infection, Environmental toxins (e.g. petrochemicals) Non-Alcoholic Fatty Liver Disease Diagnosis Laboratory Tests ALT, AST 2-3 X ULN ALT>AST if non-cirrhotic Radiology US-echogenic CT-hypo-dense MRI-bright on T1 Liver Biopsy Gold standard for Dx Distinguishes simple steatosis from steatohepatitis Treatment None established Treat predisposing conditions Weight loss (not rapid!) Control of blood sugars Treat lipid disorders Bariatric surgery if obesity plus complications Liver transplantation if decompensated cirrhosis Can be recur after transplant

15 Case #4 47 yo woman, previously healthy, presents with jaundice and fatigue X 3 weeks PMH: thyroiditis age 30 Meds: Levothyroxine. No herbs or OTC medications SH: No alcohol, injection drug use, new sexual partners or recent travel Exam: Icteric, spider angiomata chest, palmar erythema, Abdomen: hepatomegaly, no spleen tip palpable Neuro: no asterixis Initial Laboratory Results: ALT 850 U/L, AST 770 U/L, Alkaline phosphatase 150 U/L, bilirubin 13.5 mg/dl (indirect 7.7) INR 1.4, albumin 3.2, creatinine 1.1, WBC 5.5, Hgb 11, platelets 150K Case #4 Initial Studies Diagnostic Tests HAV IgM negative, anti-hcv negative, HBsAg negative, anti-hbc negative, anti-hbs positive ANA 1:640, IgG 3220, anti-smooth muscle antibody 1:40, antimitochondrial antibody negative Ceruloplasmin normal, ferritin 505, transferrin saturation 21% Drug screen negative Abdominal imaging: ultrasound Heterogenous, slightly nodular liver; ascites, spleen size upper limits of normal; hepatic veins and portal veins patent

16 Q4 What is the best treatment for this patient? A. Referral for liver transplantation B. Prednisone C. Adefovir D. Phlebotomy E. Ursodeoxycholic acid Q4 What is the best treatment for this patient? A. Referral for liver transplantation B. Prednisone C. Adefovir D. Phlebotomy E. Ursodeoxycholic acid

17 Autoimmune Hepatitis Diagnosis Clinical Clues: Female predominant Presence of other autoimmune diseases Any age Can present acutely Diagnosis: Hepatitis pattern of liver test abnormalities (ALT>> ALKP) Autoantibodies: ANA (>1:160) most common Can be ANA negative and have anti-sma, anti-lkm (>1:80) Elevated IgG (>2 g/dl) Rule out viral hepatitis, hepatotoxicity, other causes Biopsy helpful but not essential Autoimmune Hepatitis Treatment Indications for treatment: Elevated ALT (>3 X ULN) Severe histologic disease Symptomatic liver disease Treatment: Prednisone is first line, alone or with azathioprine Other immunosuppressants if fail to respond Liver transplantation if severe acute or decompensated cirrhosis

18 Case #5: Hepatitis B 27 yo heterosexual male referred for evaluation of HBV status DATA: HBsAg positive, anti-hbs negative HBeAg negative, HBV DNA 500 IU/mL. HIV negative. ALT 25 (N), AST 20 (N) Normal total bilirubin, prothrombin time and alkaline phosphatase Sexually active, single partner. No other risk factors. PH unremarkable. No meds. FH: No known family members with HBV infection, cirrhosis or liver cancer. Q5 Which of the following are indicated in the management of this patient? A. Testing for anti-hbc IgM to exclude acute HBV B. Vaccinate for HBV as lack anti-hbs C. Vaccinate sexual and household members for HBV D. Ultrasound and alpha fetoprotein every 6 mos to screen for hepatoma E. Treatment with HBV antivirals

19 Q5 Which of the following are indicated in the management of this patient? A. Testing for anti-hbc IgM to exclude acute HBV B. Vaccinate for HBV as lack anti-hbs C. Vaccinate sexual and household members for HBV D. Ultrasound and alpha fetoprotein every 6 mos to screen for hepatoma E. Treatment with HBV antivirals Diagnostic Tests for Hepatitis B Test Acute Chronic Chronic HBV HBV HBV (inactive) (active) HBsAg anti-hbs HBeAg + - +/- anti-hbe - + +/- anti-hbc IgM anti-hbc HBV DNA* Elevated low high ALT Very elevated Normal Elevated *HBV DNA >2000 IU/mL defined as HIGH ** ALT 500 U/L typical during acute infection

20 Indications for HBV Vaccination in Adults Men having sex with men (MSM) Illicit injection drug users Persons with >1 sexual parnter last 6 mos or recent STD Healthcare workers, including laboratory personnel Staff/clients of correctional institutes and institutes with mentally handicapped individuals Persons with HIV infection Persons with chronic liver disease, endstage renal disease Travelers to areas where HBV endemnic Recipients of pooled blood products All sexual and household contacts of HBsAg+ persons MMWR, Adult Immunization Schedule in United States, October 2006 Surveillance for Hepatocellular Carcinoma Who: Any patient with cirrhosis In patients with chronic hepatitis B Asian males 40 yrs; Asian females 50 years African born 20 yrs of age Family history of liver cancer How: Abdominal imaging (ultrasound or CT scan) every 6 months Alpha fetoprotein (AFP): insufficient alone as screening test. Can add to imaging but not required. AASLD Practice Guidelines, 2005

21 Chronic HBV Infection Who Should be Treated? Treatment indicated in those with active chronic HBV disease HBsAg+ with: Elevated ALT/AST (>2 X ULN) Elevated HBV DNA levels (>2000 IU/ml) Biopsy not required but can be helpful Presence of moderate necroinflammation in patient with ALT level 1-2 X ULN If cirrhosis: all recommended to be receive treatment Lok and McMahon. Hepatology. 2007;45: Treatment Landscape in US: 2009 Generic Name Dose Duration Interferon alfa-2b 5 MU daily wks Peginterferon alfa- 2a 180 ug weekly 48 wks Lamivudine 100 mg daily HBeAg-positive Adefovir dipivoxil 10 mg daily Until anti-hbe seroconversion Entecavir mg daily HBeAg-negative Telbivudine 600 mg daily Long-term (years) Tenofovir 300 mg daily

22 HBV Management in Patients Receiving Chemotherapy All patients should be tested for HBsAg and anti-hbc Patients may experience exacerbation of HBV disease with chemotherapy Highest risk group = HBsAg positive Treat HBV during chemotherapy and for 6 months after chemo discontinued Use oral agents e.g. lamivudine, adefovir or entecavir Lower risk group = anti-hbc positive only Monitor during chemotherapy and treatment if HBV DNA levels increase or become HBsAg + Case #6 38 yo male with history of injection drug use in his 20s is found to anti-hcv positive PH: otherwise negative Meds: none Exam: Anicteric. No hepatosplenomegaly Labs: CBC normal AST 22 (N), ALT 27 (N), bilirubin 0.7 mg/dl

23 Q6 What is the next step in evaluating this patient? A. HCV RNA test B. Referral for liver biopsy C. Obtain abdominal imaging D. HCV genotype E. Repeat ALT, AST every 6 months Hepatitis C Diagnosis Screen = anti-hcv Confirmatory = HCV RNA by sensitive PCR assay ALT Normal in up to 1/3 of patients Usually <200 U/L in chronic infection Evaluation Liver function tests, platelet count Abdominal imaging Liver biopsy Used to stage disease If considering treatment HCV genotype HCV viral load

24 Who Should be Screened for Hepatitis C? Targeted Screening: Person with chronically elevated liver enzymes All HIV-infected persons History of IDU, even if remote and if only once History of receiving clotting factors prior to 1987 History of HD History of blood transfusion or organ transplantation prior to July 1992 History of percutaneous or mucosal exposure to HCVinfected blood Infants born to HCV-positive mothers MMWR 1998;47: USPHS/IDSA Guidelines Natural History of Chronic HCV Infection Resolved Exposure (Acute Phase) 15-45% Stable 55-85% Chronic 75-95% Risk Factors for Cirrhosis Male gender Heavy alcohol use Older age at time of infection Longer duration of disease HIV coinfection No prophylaxis available Consider antivirals if seroconvert and viremic 5%-25% over years Cirrhosis 3%/yr HCC 5%/yr decomp Liver Decompensation Hepatoma Alter MJ. Semin Liver Dis Freeman, Hepatology 2001

25 Anti-HCV Treatment All patients with chronic HCV should be considered for antiviral therapy HCV Consensus Statement 2003 Treatment of choice: Peginterferon plus ribavirin (combo) If contraindications for ribavirin:can use interferon monotherapy Efficacy: overall 55% achieve viral eradication PREDICTORS OF SUCCESSFUL TREATMENT OUTCOME Genotype 2 or 3 Low viral load (<2 million copies/ml or 800,000 IU/mL) Low fibrosis score (stage <2) Low BMI Non-African-American Case #7 54 yo woman with history of chronic HCV Previously treated with peginterferon and ribavirin but did not respond Exam: BP 105/60, HR 72. Anicteric, Spider angiomata. Abdomen: No fluid wave, splenomegaly Labs: AST 110 U/L, ALT 80 U/L, total bilirubin 1.3 mg/dl INR 1.1, creatinine 1.0 mg/dl, serum albumin 3.4 g/dl Platelet count 97, 000, H/H normal Abdominal US: nodular liver with no focal lesions, splenomegaly, patent portal and hepatic veins.

26 Q7 What is the most appropriate next management step? A. Referral for liver transplantation B. Referral for upper endoscopy C. Referral for liver biopsy D. Referral for HCV treatment E. Monitoring of liver function tests every 6 months Q7 What is the most appropriate next management step? A. Referral for liver transplantation B. Referral for upper endoscopy C. Referral for liver biopsy D. Referral for HCV treatment E. Monitoring of liver function tests every 6 months

27 Diagnosis of Cirrhosis (in absence of clinical signs of decompensation) Laboratory Clues: AST>ALT Low platelets (<140K) Abnormalities of liver function: INR, albumin or total bilirubin Abdominal imaging Nodular, small liver Splenomegaly Recanalized umbilical vein, intrabdominal collaterals Endoscopy: Varices and portal hypertensive gastropathy Biopsy Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency Cirrhosis Portal hypertension Liver insufficiency Variceal hemorrhage Ascites Encephalopathy Jaundice Spontaneous bacterial peritonitis Hepatorenal syndrome

28 Primary Prophylaxis for Variceal Bleeding in Patients with Cirrhosis If cirrhosis present, screening to look for varices using upper endoscopy is recommended Prophylaxis recommended if varices great than small in size Primary prophylaxis options: Non-selective beta blocker (propanolol or nadolol) ±nitrates If intolerant of beta blocker, endoscopic band ligation if varices of moderate to large size Case #7 (con t) 54 yo woman with HCV cirrhosis returns 6 months with 1 month history of progressive abdominal distention Exam: Ascites, splenomegaly, mild peripheral edema. Labs: AST 110 U/L, ALT 80 U/L, total bilirubin 2.1 mg/dl INR 1.6, creatinine 1.0 mg/dl, serum albumin 3.0 g/dl Abdominal US: Moderate ascites, nodular liver with no focal lesions, splenomegaly, patent portal and hepatic veins. Diagnostic paracentesis: albumin 1.5 g/dl, WBC 100/mm 3

29 Q8 In addition to starting diuretics, which of the following is most appropriate at this time? A. Start treatment with pegylated interferon and ribavirin B. Start prophylaxis for spontaneous bacterial peritonitis C. Start propanolol for prevention of variceal bleeding D. Referral for liver transplantation E. CT scan to look for possible hepatoma Q8 In addition to starting diuretics, which of the following is most appropriate at this time? A. Start treatment with pegylated interferon and ribavirin B. Start prophylaxis for spontaneous bacterial peritonitis C. Start propanolol for prevention of variceal bleeding D. Referral for liver transplantation E. CT scan to look for possible hepatoma

30 Decompensated Cirrhosis 100 Probability of survival Median survival ~ 9 years All patients with cirrhosis Gines et. al., Hepatology 1987;7:122 Decompensated Median survival cirrhosis ~ 1.6 years Months 180 Ascites SAAG: Serum-Ascites Gradient SAAG >1.1 g/dl (high gradient) Cirrhosis, any cause Alcoholic hepatitis Fulminant hepatic failure Budd-Chiari syndrome Portal vein thrombosis Venoocclusive disease Severe right heart failure SAAG <1.1 g/dl (low gradient) Peritoneal carcinomatosis TB peritonitis Bowel obstruction/infarction Biliary ascites Nephrotic syndrome Postoperative lymphathic leak Serositis in connective tissue disease

31 Spontaneous Bacterial Peritonitis Definition SBP: 1. Positive ascitic fld culture 2. Ascitic fld cell count 250PMN/mm 3 (0.25 X 10 9 /L) DDX: 1. Secondary bacterial ascites Clue: polymicrobial, PMN count high (>1000/mm 3 ) 2. Partially treated SBP Clue: ascitic fld count inc, but culture negative Treatment of SBP 3rd gen. cephalosporins or quinolones Avoid aminoglycosides Indications for SBP prophylaxis 1. Prior episode of SBP 2. Current active GI bleeding 3. Ascitic fluid albumin <1 g/dl Assessing Liver Disease Severity In Patients with Cirrhosis Child-Pugh Score Ascites Encephalopathy Albumin T. bilirubin INR/PT Range: 5-15 Score 7 used to guide timing of referral Model of Endstage Liver Disease (MELD) Total bilirubin Creatinine INR Range: 4-40 Score determines priority status once on the waiting list

32 Child s Score in Cirrhotics Child-Pugh-Turcotte Score (CPT) Child s B 6-10 Mild- Moderate Mild- Moderate Ascites Encephalopathy Total Bilirubin Albumin Child s A 5 None None <2 >3.5 Child s C Severe Severe >3 <2.8 INR > >2.2 Case #7 2 points 54 yo woman with known HCV cirrhosis presents with ascites Diagnostic paracentesis: albumin 1.5 g/dl, WBC 100/mm 3 No history of encephalopathy or variceal bleeding. Abdominal US: Moderate ascites, nodular liver with no focal lesions, splenomegaly, patent portal and hepatic veins. Exam: BP 105/60, HR 72. Anicteric. 2 points 1 point 2 points Ascites, splenomegaly, mild peripheral edema. Labs: total bilirubin 2.1, INR 1.6, creatinine 1.0, electrolytes normal, serum albumin 3.0 g/dl

33 Case #8 45-yr-old woman presents with jaundice. Admits to drinking 6-8 drinks per day (vodka) for past 10 years up until recent DUI and court-mandated rehab. Last alcohol 3 days ago. Meds: none. PMH: otherwise negative PE: BP 100/55, HR 80, Icteric,+ spider angiomata, muscle wasting. Abdomen non-distended, no spleen tip. No asterixis Labs: Hgb 11 g/dl, platelet 140K, WBC 3.9, ALT 250 (N <45), AST 390 (N<40), bilirubin 4.8 mg/dl, Cr 1.1 mg/dl, INR 1.2, albumin 3.5 g/dl Abdominal US: Slightly nodular, heterogeneous liver. No bile duct dilatation. Spleen = 12 cm. No ascites. Q8 Which are the following are indicated in her management? A. Referral for liver transplantation B. Upper endoscopy to assess for varices C. Liver biopsy and measurement of portal pressures D. Prednisone E. Endoscopic retrograde cholangiogram

34 Q9 Which are the following are indicated in her management? A. Referral for liver transplantation B. Upper endoscopy to assess for varices C. Liver biopsy and measurement of portal pressures D. Prednisone E. Endoscopic retrograde cholangiogram Alcoholic Liver Disease Diagnosis: History. Underreporting frequent. Lab clues: Macrocytic anemia,ast>alt (2:1 or higher) and values usx <300 U/L Acute alcoholic hepatitis Severity assessed using Discriminant Function (DF) = 4.6 X (PT seconds - control) + bilirubin (mg/dl) or encephalopathy If DF>32, predicts 50% mortality Treatment Mainstay is abstinence Liver transplantation a consideration after abstinence established Prednisone a consideration if acute alcohol hepatitis with DF>32, encephalopathy and No GI bleeding, renal dysfunction or infection