Infectious Diseases of the Liver

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Infectious Diseases of the Liver Josyann Abisaab, MD Department of Emergency Medicine New York Presbyterian Hospital – Weill Cornell Medical Center

Overview : 

Overview Viral infections Pyogenic Liver Abscess Fungal and mycobacterial infections Parasitic infections

Viral Hepatitis : 

Viral Hepatitis Hepatitis A, B, C, D, E, G, “X” CMV EBV HSV VZV HIV Yellow Fever

Clinical Presentation : 

Clinical Presentation Very mild, asymptomatic to intermittent sx to fulminant hepatic failure 4 phases of infection Asymptomatic phase of viral replication Prodromal phase: N/V, fatigue, malaise, anorexia, arthralgias, urticaria, pruritus, altered sense of taste Icteric phase: dark urine + light stools, jaundice, RUQ pain & hepatomegaly Final phase: convalescence Chronic viral infection

Typical ED patient with Hepatitis : 

Typical ED patient with Hepatitis Hx: young male, c/o fatigue, anorexia, abdo pain, dark urine, light stool, transient rash, arthralgia and pruritus Exam: Jaundiced, dehydrated, with an enlarged tender liver, possibly a rash + low grade fever Labs: nl WBC, nl alkaline phosphatase, bili 9.0, AST 700, ALT 1200, Gluc 60. Imaging: sono or CT rarely indicated Rx: supportive

Indications for Admission : 

Indications for Admission Encephalopathy PT > 15 Fluid or electrolyte imbalance Intractable vomiting Hypoglycemia Bili > 20mg/dl Severe underlying disease Age > 50 years Immunosuppression

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Hepatitis A Epidemiology 125,000-200,000 cases/yr in U.S. 100 deaths/yr from fulminant hepatitis A 15% of infected individuals develop prolonged or relapsing disease Accounts for 20-25% of clinical hepatitis Most often affects persons 5-14 years-old Causes acute hepatitis, no chronic state Transmission: fecal-oral route

Risk Factors for Hepatitis A : 

Risk Factors for Hepatitis A Close personal contact with an infected individual Association with daycare centers or young children International travel Water borne outbreaks with raw oysters and clams IV drug use & transfusion (rare)

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Hepatitis A Clinical course Most cases asymptomatic, esp. children If symptomatic fatigue, nausea, myalgias, jaundice, fever More severe presentation in adults vs. children Diagnosis Elevated ALT>AST, total bilirubin, hepatitis A IgM + Prognosis Complete recovery in almost all patients <1% develop fulminant liver failure

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Hepatitis A Prevention Early recognition and isolation of infected patients Hygiene- Hand washing Vaccination- recombinant vaccine/Havrix,Vaqta

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Hepatitis B Epidemiology 350 million carriers worldwide More than 1 million HBV related deaths annually (WHO) 10% of adults and 90% of children become carriers Transmission: parenterally, sexually, vertical transmission Risk factors: IV drug use, prostitutes, homosexual men, Asian population, hemodialysis patients, health care workers

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Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ³8% - High 2-7% - Intermediate <2% - Low

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Hepatitis B

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Hepatitis B Clinical course Symptoms of fatigue, myalgias, jaundice, nausea, vomiting, rash Jaundice for 1-2 months, elevated ALT, AST, T. bili Fulminant hepatitis- rapid clinical decline, marked elevation of liver function tests, encephalopathy Extrahepatic manifestations- polyarteritis, glomerulopathy, Guillain Barre

Hepatitis B Anatomy : 

Surface DNA Core Hepatitis B Anatomy

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Hepatitis B Diagnosis Laboratory findings: HepBsAg positive HepBcore IgM positive HepBeAg positive HBVDNA positive Hep B surface antibody confers immunity

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Acute Hepatitis B Virus Infection with Recovery Total anti-HBc IgM anti-HBc anti-HBs HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Typical Serologic Course Titer Weeks after exposure

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Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Weeks after Exposure Titer IgM anti-HBc Total anti-HBc HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe 0 4 8 12 16 20 24 28 32 36 52 Years

Hepatitis B : 

Hepatitis B Prognosis <1% develop fulminant hepatic failure 5-10% develop chronic hepatitis 30% of chronically infected develop cirrhosis

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Hepatitis B Prevention Early recognition and education Adequate hygiene and universal precautions Vaccination- health care workers, high risk groups, children born to infected mothers (HBIG) Vaccine- recombinant vaccine given at 0, 1, 6 months, ?booster at year 7

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Hepatitis B Chronic Hepatitis B Failure to clear Hep B s Ag after 6 months Cause of cirrhosis and hepatocellular carcinoma Treatment includes interferon 5 million units daily for 16 weeks ~30% sustained response Lamivudine 100mg daily- high relapse rate once discontinued Liver transplantation for patients with cirrhosis

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Hepatitis D Only occurs with hepatitis B~10% of cases Superinfection vs. coinfection Highest incidence in IV drug users Results in greater morbidity and decreased response to interferon Prevented with vaccination against hepB

Hepatitis C (the silent epidemic) : 

Hepatitis C (the silent epidemic) “We stand at the precipice of a grave threat to our public health… It affects people from all walks of life, in every state, in every country. And unless we do something about it soon, it will kill more people than AIDS.” C. Everett Koop Former US Surgeon General

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Hepatitis C Epidemiology 200 million carriers worldwide, 4.5 million in US 80% of infected patients develop chronic infection Transmission: parenterally, low vertical and sexual transmission Risk factors- IV drug use, blood transfusion history, hemophiliacs, dialysis, prison, inhalational cocaine?, tatoos? #1 indication for liver transplantation 1-4% incidence of hepatocellular carcinoma

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Hepatitis C Clinical course Only 25% of infected individual report symptoms 10-20 years may elapse from infection to diagnosis 80% of infected individuals develop chronic hepatitis and 20% develop cirrhosis Diagnosis Measure ALT Hepatitis C antibody Hepatitis C viral titer (HCVRNA) Liver biopsy if elevated ALT and candidate for therapy

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Hepatitis C

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Hepatitis C Therapy Interferon plus ribavirin for 6-12 months 35% sustained response Side effects Interferon- flu like symptoms, lowering blood counts, thyroid disease, depression, hair loss Ribavirin- teratogenicity, hemolytic anemia

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Hepatitis E and G Hepatitis E RNA virus similar to hepatitis A Spread by fecal oral route, 2 week incubation Rare in U.S. , more common in Africa and India Severe course in pregnancy, no chronic state Hepatitis G 0.2% acute hepatitis, 900-2000 infections/yr Exact role not known, probably not a pathogen

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Review of Viral Hepatitis A B C E genome RNA DNA RNA RNA age young all all adults onset abrupt insidious insidious abrupt incubation 15-50 28-160 14-160 15-45 rash no yes no yes fever yes no no yes jaundice yes possible no yes Pregnancy mild mod mild severe

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Review of Viral Hepatitis A B C E chronic no yes yes no liver cancer no yes yes no Transmission oral yes unlikely no yes IV rare yes yes no sexual uncommon yes yes no perinatal no yes low no

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Markers of viral hepatitis Marker Significance HAV IgM acute hepatitis A infection HAV IgG prior hepatitis A infection, immunity HBVsurface antigen acute or chronic hepatitis B HBV core IgM acute hepatitis B HBV core IgG prior hepatitis B infection HBV surface antibody immunity to hepatitis B HBV e antigen infectious hepatitis B HCV Ig G antibody infection with hepatitis C HBVDNA viral titer of HBV HCVRNA viral titer of HCV

Risk for Occupational Transmission : 

Risk for Occupational Transmission HBV If HBsAg & HBeAg + : 22-33% If HBsAg + only: 1-6% HCW with antibodies have no risk Risk less with body fluids HBV can survive in dried blood at room temp on environmental surfaces for at least 1 week HCV Needlestick: 1.8% Rarely from mucous membrane exposures to blood No transmission from intact or nonintact skin exposures to blood Exposure to body fluids not quantified but expected to be low

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High Moderate blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk Concentration of Hep B virus in Body Fluids

Blood Transfusion Risk : 

Blood Transfusion Risk Hep B: 1/66,000 units of blood Hep C: 1/103,000 units of blood

Post Exposure Prophylaxis : 

Post Exposure Prophylaxis Hep A Household & sexual contacts of known cases Exposure to contaminated water or food before cases begin to appear All staff and attendees of daycare centers caring for children in diapers with any known case among children or staff Hygiene Dose: IG 0.02 ml/Kg IM

Post Exposure Prophylaxis : 

Post Exposure Prophylaxis Hep B Wash wound or skin with soap & water/flush mucosa Human Bites: reciprocal exposure Rape victims: Rx has to be <14 days Pregnancy & Lactation: HBIG + vaccine safe Efficacy of HBIG + Hep B vaccine > 90% (preferably within 24 hours) Side effect of vaccine: pain + mild fever/anaphylaxis 1 in 600,000 doses HBIG prepared from pooled human plasma: no transmission of HBV, HCV or HIV Side effect of HBIG: local pain,urticaria, angioedema, rarely anaphylaxis Testing of needles or sharps is not recommended

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Source: CDC

Hepatitis B vaccine schedule : 

Hepatitis B vaccine schedule 1st dose in ED or UC 2nd dose: 1-2 months 3rd dose: 4-6 months

Postexposure Management of HCV : 

Postexposure Management of HCV Prevention of HCV by IG is not indicated No clinical trials conducted to assess use of Interferon Antivirals are not FDA approved Early identification of chronic disease Source: check anti-HCV Person exposed: baseline anti-HCV + ALT, f/u at 4-6 weeks, 4-6 months

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess Background Relatively rare Described since the time of Hippocrates (400 BC) Frequency 8-16 cases per 100,000 hospitalized patients Increased rates in specific populations eg. Crohn’s Disease Age Most common toward the sixth and seventh decades of life

Anatomy of the Liver : 

Anatomy of the Liver

Pyogenic Liver Abscess : 

Pathophysiology Most common source is Biliary Tract Disease (60%) Cholecystitis, ascending cholangitis, stricture, malignancy, congenital diseases Portal pylephlebitis (24%) Hematogenous dissemination (15%) Endocarditis, pyelonephritis Contiguous spread Cryptogenic Trauma Secondary infection Amebic abscess, hydatid cystic cavities, metastatic and primary hepatic tumors Pyogenic Liver Abscess

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess History Fever (90%) Chills Anorexia + malaise Weight loss Abdo pain (50%) Cough or hiccoughs Exam General appearance Jaundice (25%) Tender hepatomegaly Hypochondrial or epigastric mass Decreased breath sounds at the RLL

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess Lab studies High WBC (77%) High ESR High Alkaline Phosphatase is the most common abnormality Elevations of AST, Tbili variable Blood cultures + (50%) Imaging studies CXR: raised right hemidiaphragm & pleural effusion (50%) Ultrasound (sensitivity 80-90%): hypoechoic masses with irregularly shaped borders CT scan (sensitivity 95-100%): well demarcated hypodense areas, gas seen in 20%

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess Microbiology Polymicrobial involvement with aerobes and anaerobes Biliary tree: enteric gram – bacilli and enterococci Pelvic or colonic source: mixed flora incl. Aerobic and anaerobic especially B. fragilis Hematogenous spread: Staph aureus or Strep milleri

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess Management Antibiotics: cephalosporin and flagyl Duration: 4-6 weeks for solitary lesions with adequate drainage Up to 12 weeks for multiple abscesses Procedures: Percutaneous needle aspiration under ultrasound guidance Percutaneous catheter drainage Surgery: peritonitis, diverticular abscess, failure of drainage attempts, complicated multiloculated, thick walled abscess

Pyogenic Liver Abscess : 

Pyogenic Liver Abscess Consultations Diagnostic interventional radiology General surgery GI ID Prognosis Mortality: 5-30% Indicators of poor prognosis: Multiple lesions Severity of underlying medical conditions Presence of complications Delay in diagnosis Hgb < 11, bili > 1.5, WBC >15, alb < 2.5, elevated PTT

Fungal & Mycobacterial Infections : 

Fungal & Mycobacterial Infections Fungal Immunocompromised patients Hematogenous dissemination Most occur in leukemic patients: Candida albicans Aspergillus, Actinomyces, Cryptococcus, Histoplasma Mycobacterial Usually a miliary process High suspicion if multiple 1cm or less liver lesions, especially in HIV + patient

Parasitic infections : 

Parasitic infections Amebic Liver Abscess Echinococcal or Hydatid Disease Liver Flukes Clonorchis sinensis Opisthorchis species Fasciola hepatica (Fascioliasis) Schistosoma species (Schistosomiasis) Ascariasis Toxoplasmosis Strongyloides Malaria

Amebic Liver Abscess : 

Amebic Liver Abscess Pathogenesis - Protozoan parasite: Entamoeba histolytica Exposure via fecal-oral route Humans are the principal host Source of infection is the cyst-passing chronic patient or asymptomatic carrier

Amebic Liver Abscess : 

Amebic Liver Abscess Epidemiology Highest endemic activity in Mexico, India, East and South Africa, portions of Central & South America. 40 to 50 million people worldwild become symptomatic with amebic colitis or ALA (WHO 1995) 40,000 to 100,000 deaths /year Increase in male homosexuals with/without HIV

Amebic Liver Abscess : 

Amebic Liver Abscess Typical patient in US: young hispanic male with a travel hx to an endemic area or emigration from Mexico or Southeast Asia Age: 20-40 Male:Female ratio = 10:1 Liver is the commonest extraintestinal site of infection 10% of affected patients develop liver abscesses 80% of abscesses develop in the right lobe Hx of Alcohol abuse is common

Amebic Liver Abscess : 

Amebic Liver Abscess Clinical Most common: fever, chills, nausea, weakness, malaise and RUQ or epigastric pain Diarrhea (20%) Jaundice is uncommon Exam: RUQ tenderness, hepatomegaly, decreased BS in the Right lung base or a pleural rub Labs: High WBC + ESR, hct < 35, abnormal LFT’s Latex agglutination assay + (90%) Stool microscopy or stool antigen tests helpful only in < 30% Imaging: CXR, Sono, CT, MRI, A99m Tc nuclear hepatic scan

Amebic Liver Abscess : 

Amebic Liver Abscess Management Metronidazole 750mg po tid for 10 days (90% cure rate) Luminal agent for Rx of asymptomatic colonization state Ultrasound guided aspiration: Cavity size > 5cm Left lobe liver abscess No response to drug Rx within 5-7 days Aspiration produces a typical “anchovy sauce” appearing pus

Amebic Liver Abscess : 

Amebic Liver Abscess Complications Rupture into peritoneum, pleural cavity, pericardium Peritonitis, paralytic ileus, fulminant colitis, colonic perforation or toxic megacolon Compression of biliary tree causing obstructive jaundice Inferior vena cava obstruction Bacterial superinfection ARDS & sepsis Brain abscess

Amebic Liver Abscess : 

Amebic Liver Abscess Prognosis Good in uncomplicated cases (<1% mortality) Bad if pulmonary complications (20% mortality)

Echinococcal disease : 

Echinococcal disease Due to infection with the helminth Echinococcus Granulosa Man is an accidental intermediate host Adult worm found normally in the dog and sheep intestine Seen in Mediterranean areas, Australia and South America Liver is the commonest organ involved Cysts are unilocular, can be up to 20cm in diameter and may be multiple

Echinococcal Disease : 

Echinococcal Disease Clinical RUQ pain (60%) Jaundice (15 %) Skin rashes, pruritus, allergic reactions Cysts can rupture causing bronchobiliary fistula Eosinophilia (30%) Dx confirmed by indirect haemagglutinin assay Cyst can be imaged by sono or CT Management Aspiration/high failure rate Pharmacological treatment is not curative: albendazole, mebendazole Surgical removal is preferred Recurrence rate 5% at 5 years