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Liver and Pancreas. AST/ALT. ABNORMAL LIVER TESTS. > 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
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AST/ALT ABNORMAL LIVER TESTS • > 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
HBV Scenarios 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 IFN-ineligible 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
Other liver tests ABNORMAL LIVER TESTS • Autoimmune hepatitis (ANA, ASMA, Anti-liver/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
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