Alcoholic Hepatitis Jaundice, fever, ascites, HE, AST/ALT > 2 with AST/ALT < 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
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 HBsAganti-HBsanti-HBc IgM anti-HBc IgG HBeAgDX 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 years of infection – 5 %/yr risk to develop HCC in those with cirrhosis 5% sexual transmission over 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
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.IFN- ineligible
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. 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.
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
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 Most common cause is cirrhosis Manifestations: Hepatic Encephalopathy Gastro-esophageal Varices Ascites
Approach to the Patient with 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 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.
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
Liver Biochemistry Pattern DiseaseAPTBiliHistorical Features Diagnostic Evaluation Primary biliary cirrhosis ↑↑↑More common in women, fatigue, pruritus Antimitochondria l antibodies present in 95%, liver biopsy Primary sclerosing cholangitis ↑↑↑More common in men, history of inflammatory bowel disease Cholangiography Large bile duct obstruction ↑↑↑Pain and feverCholangiography Drug-induced cholestasis ↑↑↑History of drug/medication use within 3 months, often of a drug previously associated with liver injury Improvement with cessation Infiltrative liver disease ↑↑CT, MRI, liver biopsy
Liver Enzyme Pattern DiseaseALTASTHistoryDX Viral hepatitis A↑↑↑↑↑Fecal oral exposure (IgM anti-HAV) Viral hepatitis B↑↑↑↑↑Blood/body fluid exposure (IgM anti-HBc) and + (HBsAg) Viral hepatitis C↑↑↑Recent intravenous drug use (HCV RNA); variable presence of (anti-HCV) Alcoholic hepatitis↑↑↑Heavy alcohol use, either binge or chr AST:ALT >2, AST usually <500 Drug-induced hepatitis↑↑↑↑↑↑H/of drug/med use within 3 mo Absence of other liver disease Fatty liver, nonalcohol↑↑↑Late pregnancy, amiodarone History of medication use, absence of other liver disease Ischemic hepatitis ↑↑↑↑ Severe hypotension rapid improvement with resolution of hypotension Acute liver failure↑↑↑↑Ingestion of an associated agent; rapid progression Signs of impaired hepatic synthetic function
Liver Enzyme Pattern DiseaseALTASTHistorical FeaturesDiagnostic Findings Viral hepatitis B↑↑↑Fecal oral exposure, endemic area HBsAg; may have hepatitis B DNA (HBV DNA) Viral hepatitis C↑↑↑IVDA, blood tx prior to 1992, Vert Tx, parenteral expos Anti-HCV, HCV RNA Fatty liver, nonalcohol ↑↑↑Presence of metabolic syndrome (obesity, insulin resistance, hypertriglycer) Absence of other liver dz imaging shows fat Alcoholic liver disease ↑↑↑Remote history of heavy alcohol use Absence of other liver disease Autoimmune hepatitis ↑↑↑More common in womenPositive, ANA and anti– SMA Hemochromatosi s ↑↑Arthritis, diabetes, family history Ferritin (>1000) and iron sat (>55%), HFE gene mutations Wilson disease↑↑ Young, movement disorders, psychiatric disease, KF rings Hemolysis, low ALP, low ceruloplasmin α1-Antitrypsin deficiency ↑↑Lung diseaseLow 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
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 ABNORMAL LIVER TESTS
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