Liver and Pancreas ABNORMAL LIVER TESTS AST/ALT • > 300 – Viral, toxin-induced, ischemia, meds • < 300 – EtOH Hepatitis, cholestasis • AST/ALT ratio – > 2 = EtOH – < 1 = Viral or obstructive Alcoholic Hepatitis • Jaundice, fever, ascites, HE, AST/ALT > 2 with AST/ALT < 300-400.Increased WBC • PATH: Steatosis, Fibrosis,Mallory bodies • Treatment: • If MDF > 32 start prednisone 40 mg X 4 wks • After 7 days on steroids if no improvement and Lillie score >.45 Stop Steroids. • If steroids are C/I add pentoxifiline to prevent HRS DILI • • • • • • Acetaminophen Antibiotics: Bactrim, Augmentin, E-cin Phenytoin Valproic acid Immunomodulators INH Viral Hepatitis: Transmission • Fecal-Oral: Hepatitis A and E • Sexual: Hepatitis B and D; also C (to a lesser extent) • Note: Hepatitis D requires coexisting Hep. B infection Viral Hepatitis: Clinical • Symptoms include fatigue, anorexia nausea and vomiting • Lab shows elevated AST/ALT and bili • May resolve, turn fulminant, or become chronic Hepatitis A • • • • • • • Fecal-oral transmission Symptoms: Adult > children Transplacental transmission occurs No carrier states, rarely fulminant Can have cholestasis for up to 6 mos Vaccine: Patients with liver dz/risks/ travelers Acute infection: + IgM anti-HAV, Vaccination: + IgG anti-HAV • IG prophylactic for Hep A • HAV Vaccination 2 doses 6-12 months apart. Hepatitis B • Incubation 1-6 months • Transmitted sexually, parenterally, mucous membrane exposure • Can present with serum sickness (fever, arthritis, urticaria, angioedema) • Associated with polyarteritis nodosa (PAN) Extra intestinal Manifestations of Hep B • • • • • • Polyarteritis Nodosa Arthritis Glomerulonephritis Urticaria Mixed Cryoglobulinemia Polyneuropathy Hepatitis B Serology HBV Scenarios HBsAg anti-HBs anti-HBc IgM anti-HBc IgG HBeAg DX + - + - + Acute infection + - - + + Carrier - + - - - Vaccinated - Exposed Immune - Acute Window - Exposed Ab lost - - + - - + - + - + HepB vaccine/prophylaxis • 95% of immunocompetent pts develop antibody (anti-HBs) • Only 50% of HD pts develop antibody • May be given to pregnant pts • 3 doses at 1, 2 and 6 months • HBIG Alone: – sexual contacts of carriers and household members of acute Hep B • HBIG + vaccine (exposed is HBsAg negative) – blood exposure to pt w/acute Hep B – newborns of Hep B mothers Treatment of CHB • HBeAg + HBV DNA > 20000, ALT > 2 x ULN • Observe for 6 months and treat if no spontaneous conversion. • Consider Liver Bx • Rx: Peg IFN o • Entecavir, tenofovir, telbivudine • Continue Rx for 6 months after seroconversion Treatment of CHB • • • • HbeAG – HBV DNA > 20000 , ALT > 2 x ULN RX Continue till HBsAG loss Hepatitis C • Most common liver disease in the US • IVDU, cocaine use, prisons, blood products prior to 1990, tattoo • Genotype 1 most common in the US • 85 % of Hep C infected become chronic – 25% cirrhosis post 20-25 years of infection – 5 %/yr risk to develop HCC in those with cirrhosis • 5% sexual transmission over 10-20 yrs • <5% trans placental transmission. HIV co-infection increases transmission rate. Serological Tests • Third generation anti-HCV+ >95% sensitive • If high pre-test probability and anti-HCV negative can do PCR testing (more often in renal failure or transplant) • Genotype testing required for treatment candidates only Extrahepatic Manifestations • • • • Glomerulonephritis/MPGN Cryoglobulins Porphyria cutanea tarda (PCT) Thrombocytopenia – Autoantibody – ITP • • • • Neuropathy Thyroiditis Sjogren’s Syndrome Inflammatory arthritis Recommended regimen for treatment-naive patients with HCV genotype 1 who are eligible to receive IFN. Daily sofosbuvir RBV plus weekly PEG for 12 weeks is recommended for IFN-eligible persons with HCV genotype 1 infection, regardless of subtype. Recommended regimen for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN. Daily sofosbuvir RBV for 12 weeks is recommended for IFNineligible patients with HCV genotype 1 infection, regardless of subtype. Recommended regimen for treatment-naive patients with HCV genotype 2, regardless of eligibility for IFN therapy: Daily sofosbuvir RBV for 12 weeks is recommended for treatment-naive patients with HCV genotype 2 infection. Recommended regimen for treatment-naive patients with HCV genotype 3, regardless of eligibility for IFN therapy: Daily sofosbuvir RBV for 24 weeks is recommended for treatment-naive patients with HCV genotype 3 infection. Hepatitis D • Requires coexistent B • Usually found in IVDA • Coinfection: does not worsen acute Hep B or risk for chronic state • Superinfection: frequently severe/fulminant • Dx: Anti-HDV IgM Hepatitis E • • • • Monsoon flooding Fecal-oral route No chronic forms Fulminant hepatitis in 3rd trimester of pregnancy • A 30 y/o female presents with c/o fatigue,arthralgias,weight loss, amenorrhea. PE reveals Icterus and HSM. No h/o alcohol or drug abuse. No FH of Liver disease.Labs: T.Bili 6mg/dl, AST 300 U/L,ALT350 U/L, ALP 100 U/ml, Albumin 2.9 g/dl. Iron studies are normal. Hepatitis profile and HIV is negative. Which of the following are correct: • • • • 1. ANA and ASMA are likely to be positive 2. Liver Biopsy should be done to confirm Dx 3. She will likely respond to steroid therapy 4. All of the above are correct. Autoimmune Hepatitis • • • • • • • • • • AIH: Asymptomatic mild disease to Fulminant Liver failure. Fatigue, Jaundice, Maliase Type I:ANA +, ASMA +, Increased IG,SLA/LP Ab Common in USA Type II: LKM1 Common in Europe, poor prognosis, Rx failures RX: Steroids Immunomodulators. Primary Biliary Cirrhosis • • • • • Usually middle aged women Pruritis, fatigue Increased alk phos The clue: elevated Antimitochondrial Antibodies (AMA) – Anticentromere antibodies – Associated with sicca syndrome and scleroderma • Treat with ursodiol Primary Sclerosing Cholangitis • An autoimmune fibrosis of large bile ducts • Clinical: RUQ pain, fatigue, weight loss • 70% of cases associated with ulcerative colitis • Increased risk of cholangiocarcinoma • Diagnose with ERCP – Beading of the bile ducts on ERCP/MRCP – 10-15% get bile duct carcinoma NAFLD • • • • • • • • • • • NAFLD: Steatosis NASH: Steatohepatitis Characteristics: Metabolic Syndrome Elevated AST/ALT Liver Biopsy Dx of exclusion: RX: RF Modification Antioxidants Oral hypoglycemics ABNORMAL LIVER TESTS Other liver tests • Autoimmune hepatitis (ANA, ASMA, Antiliver/kidney microsomal, anti-SLA) • PBC (AMA) • PSC (p-ANCA 70%) • Hemochromatosis Iron Saturation >45% • Wilsons Disease (low ceruloplasmin, incresed serum and urine Cu) • Alfa 1 antitrypsin def Hemochromatosis • Most common genetic disease in Caucasians • Iron deposits in liver, heart, pancreas, pituitary, Joints • Bronze pigmentation, new onset DM,arthritis,hypogonadism. • Can lead to cirrhosis and HCC • Iron Sat > 45% • Increased Ferritin • Abnormal Lft’s • HFE gene mutation C282Y and H63D • RX: Phlebotomy • Goal ferritin < 50 Wilson’s Disease • Rare Autosomal Recessive d/o 1:30000 • Increased cooper uptake and decreased biliary excretion. • May present as fulminant liver failure • Neuropsychiatry symptoms • Increased AST/ALT • Low ALP • Low Cerruloplasmin • Increased urinary copper excretion • KF rings on slit lamp Liver Diseases in Pregnancy 1st Trimester 2nd Trimester 3rd Trimester Acute viral hepatitis A-E Acute viral hepatitis A-E Acute viral hepatitis A-E Hyperemesis GV Gallstones Gallstones Gallstones Herpes Hepatitis Herpes Hepatitis ICP ICP AFLP Pre-eclampsia HELLP Portal HTN • Increased portal blood flow: Increased cardiac index Splanchnic vasodilation Hypervolemia • Increased resistance to portal blood flow: Fixed resistance from fibrosis Dynamic resistance • RX: • • • • NSBB Octreotide Diuretics TIPS Portal HTN • • • • • Most common cause is cirrhosis Manifestations: Hepatic Encephalopathy Gastro-esophageal Varices Ascites Approach to the Patient with Ascites ASCITES Workup • Need to know if ascites is CHF, cirrhosis or malignancy (exudate) • Serum-ascites albumin gradient > 1.1 = transudate (Portal HTN) • If ascites protein > 2.5, then CHF • If ascites protein < 2.5, then cirrhosis • <1.1 = ascites is NOT from portal hypertension – “Higher SAAG = higher pressure” ASCITES Workup Tap all new ascites • Tap all ascites in cirrhotics with clinical change • Labs – < 250 cells/μl – 1 neutrophil/250 RBC – 2 lymphocyte/750 RBC – Innoculate cultures at the bedside – Gram stain • If TB is suspected, you need a peritonal bx ASCITES • • • • • Treatment 2g Na restriction/day No benefit in restricting fluids Spironolactone 100mg/day + Lasix 40mg/day Large volume paracentesis TIPS for paracentesis-resistant ascites SBP • Translocation of bacteria across they bowel wall into susceptible ascites. • Subclinical • Fever, Abd pain,encepahlopathy • DX: • PMN > 250 • GN organisms E.coli most common • Treat SBP with 3rd generation cephalosporin IV for 5 day and then PO Abx • Pplx with oral quinolones after SBP • IV Albumin to prevent HRS. Hepatic Encephalopathy • Ppting Factors: • GI bleed, SBP, Sepsis, sedatives, constipation, electrolyte abnormalities, acute liver injury, HCC, surgery. • RX: • Recognize and Correcting ppting factors • Correct electrolytes. • Lactulose • Rifaximin. Hepatorenal syndrome (HRS) • • • • • • HRS Type I: Rapid decline in renal function HRS Type II: Chronic usually due to refractory ascites. DDX: ATN, Pre-renal DX: Sr Creatinine > 1.5 No improvement after holding diuretics and volume expansion with IV Albumin • Absence of shock, hypotension,proteinuria,nephrotoxics • Low urine sodium. HRS • • • • • • Rx: Avoiding and holding all nephrotoxics. Hold diuretics IV Albumin Midodrine and octreotide OLT is the definitive treatment Fulminant Hepatic Failure • Jaundice and hepatic encephalopathy in the absence of chronic liver disease. • Acetaminophen is the most common cause in US ( worsened by alcohol, malnutrition and fasting state) • Acute viral hepatitis is the most common cause world wide. • Other meds: INH, NSAIDS, herbal meds • Other causes: AIH, BCS, AFLP, HELLP, Amanita Phalloids Fulminant Hepatic Failure • Complications: Hypoglycemia, Cerebral edema,coagulopathy,infection • RX; • Supportive care in ICU • Early recognition and transfer to the transplant center. • NAC for acetaminophen toxicity • Acyclovir for HSV hepatitis. • Pen G for mushroom toxicity • Antiviral for acute hepatitis B Disease Liver Biochemistry Pattern AP TBili Primary biliary cirrhosis ↑↑ ↑ Primary sclerosing cholangitis ↑↑ ↑ Large bile duct obstruction Drug-induced cholestasis ↑↑ ↑ ↑↑ ↑ Infiltrative liver disease ↑↑ Historical Features More common in women, fatigue, pruritus Diagnostic Evaluation Antimitochondria l antibodies present in 95%, liver biopsy More common in Cholangiography men, history of inflammatory bowel disease Pain and fever Cholangiography History of Improvement drug/medication with cessation use within 3 months, often of a drug previously associated with liver injury CT, MRI, liver biopsy Liver Enzyme Pattern Disease Viral hepatitis A ALT ↑↑↑ AST ↑↑ Viral hepatitis B ↑↑↑ ↑↑ Viral hepatitis C ↑↑ ↑ Alcoholic hepatitis ↑ ↑↑ Drug-induced hepatitis ↑↑↑↑ ↑↑ Fatty liver, nonalcohol ↑↑ ↑ Ischemic hepatitis ↑↑↑↑ ↑↑↑↑ Acute liver failure ↑↑↑ ↑ History Fecal oral exposure Blood/body fluid exposure Recent intravenous drug use DX (IgM anti-HAV) (IgM anti-HBc) and + (HBsAg) (HCV RNA); variable presence of (anti-HCV) Heavy alcohol use, AST:ALT >2, AST either binge or chr usually <500 H/of drug/med Absence of other use within 3 mo liver disease Late pregnancy, amiodarone History of medication use, absence of other liver disease Severe rapid hypotension improvement with resolution of hypotension Ingestion of an Signs of impaired associated agent; hepatic synthetic rapid progression function Disease Liver Enzyme Pattern ALT AST Viral hepatitis B ↑↑ ↑ Viral hepatitis C ↑↑ ↑ Fatty liver, nonalcohol ↑↑ ↑ Alcoholic liver disease Autoimmune hepatitis ↑ ↑↑ ↑↑ ↑ Hemochromatosi ↑ s ↑ Wilson disease ↑↑ ↑↑ α1-Antitrypsin deficiency ↑ ↑ Historical Features Diagnostic Findings Fecal oral exposure, endemic HBsAg; may have area hepatitis B DNA (HBV DNA) IVDA, blood tx prior to 1992, Anti-HCV, HCV RNA Vert Tx , parenteral expos Presence of metabolic syndrome (obesity, insulin resistance, hypertriglycer) Remote history of heavy alcohol use More common in women Arthritis, diabetes, family history Absence of other liver dz imaging shows fat Absence of other liver disease Positive , ANA and anti– SMA Ferritin (>1000) and iron sat (>55%), HFE gene mutations Young, movement disorders, Hemolysis, low ALP, low psychiatric disease, KF rings ceruloplasmin Lung disease Low serum A1AT, liver biopsy ABNORMAL LIVER TESTS History Pearls • Pruritus/Cholestasis • PBC, PSC • Undercooked food, oysters, daycare – Hep A • ICU, hypotension, Rt. Sided heart failure – Hepatic congestion • Chronic pancreatitis – Stenosis of CBD ABNORMAL LIVER TESTS History Pearls • Neurological/Psych findings – Wilson’s disease • Metabolic syndrome – Fatty liver • Hyperpigmentation – Hemochromatosis or PBC • Kayser-Fleischer rings and sunflower cataracts – Wilson’s disease ABNORMAL LIVER TESTS History Pearls • Splenomegaly – Portal HTN or infiltrative process • Pulsatile liver – Tricuspid insufficieny • Hepatic bruits – HCC Acute Pancreatitis • • • • • • Alcohol Biliary Tract Disease Trauma Post ERCP Hyperlipidemia Pancreatic Malignancy Causes of Acute Pancreatitis Obstructive Toxins/Drugs Metabolic Infectious Vascular Gallstones (45%) Pancreas divisum Malignancy Choledochocele Parasites (Ascaris lumbricoides) Alcohol (35%) Azathioprine Sulfa drugs Aminosalicylates Metronidazole Pentamidine Didanosine Hyperlipidemia Hypercalcemia Viral (Cytomegalovirus, Epstein-Barr virus) Parasites (Toxoplasma, Cryptosporidium) Ischemia Vasculitis Poor Prognostic Indicators In Pancreatitis • • • • • • • • • SBP < 90 , HR > 130 PO2 < 60 mmHg Urine out put < 50ml/hr or BUN/Cr Elevation GI Bleeding Pancreatic necrosis HCT > 44 CRP > 150 Apache score > 8 Ranson score > 3 Complications of Pancreatitis • Sepsis; Necrosis, infected pseudocyst,Abscess • Early: Shock, ARDS, GIB, DIC, Uremia,hypocalcemia Splenic infarction & rupture, Pl Effusion. Late: Phlegmon, Pseudocyst, abscess Ascites, Pleural Effusion Splenic Vein thrombosis– GV--GIB Ranson Criteria Admission • Age > 55 • WBC > 15K • Glucose > 200 • AST > 250 • LDH > 350 During 48 hrs • PO2 < 60 mmHg • Drop in HCT > 10 % • BUN increases > 5mg/dl • Calcium < 8 mg/dl • Fluid sequestration Pearls • Acute Pancreatitis is a clinical and lab Dx and not imaging • Alcohol and Gall Stones most important causes • Prophylactic Abx (Imipenum) in necrotising pancreatitis • Early enteral Feeding is preferred. Pancreatic Adenocarcinoma • Risk Factors: Age, Smoking, Chronic pancreatitis,Hereditary pancreatitis, Obesity, Fatty diet • Manifestation: Pain radiating to back, Wt Loss, jaundice, Painless jaundice due obstruction of CBD by pancreatic head mass Diagnosis: CT-Scan pancreas protocol, EUS, MRI, ERCP GOOD LUCK !