Infectious Diseases of the Liver

Josyann Abisaab, MD

Department of Emergency Medicine

New York Presbyterian Hospital –

Weill Cornell Medical Center

Overview

• Viral infections

• Pyogenic Liver Abscess

• Fungal and mycobacterial infections

• Parasitic infections

Viral Hepatitis

• Hepatitis A, B, C, D, E, G, “X”

• CMV

• EBV

• HSV

• VZV

• HIV

• Yellow Fever

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

• 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

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

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

Geographic Distribution of HAV InfectionGeographic Distribution of HAV Infection

Anti-HAV Prevalence

High

Intermediate

Low

Very Low

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)

Hepatitis AClinical 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

Hepatitis A

Prevention•Early recognition and isolation of infected patients

•Hygiene- Hand washing

•Vaccination- recombinant vaccine/Havrix,Vaqta

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

Geographic Distribution of Chronic HBV Infection

HBsAg Prevalence

8% - High

2-7% - Intermediate

<2% - Low

Cirrhosis 2%

Chronic hepatitis

5%

Acute hepatitis

35%

Asymptomatic 58%

Hepatitis B

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

Surface

DNA

Core

Hepatitis B Anatomy

Hepatitis B

Diagnosis

• Laboratory findings:

•HepBsAg positive

•HepBcore IgM positive

•HepBeAg positive

•HBVDNA positive

• Hep B surface antibody confers immunity

Acute Hepatitis B Virus Infection with Recovery

Symptoms

HBeAg anti-HBe

Total anti-HBc

IgM anti-HBc anti-HBsHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Typical Serologic Course

Titer

Weeks after exposure

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

Prognosis

• <1% develop fulminant hepatic failure

• 5-10% develop chronic hepatitis

• 30% of chronically infected develop cirrhosis

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

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

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)

“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 KoopFormer US

Surgeon General

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

Hepatitis CClinical 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

Hepatitis C

cirrhosis20%

chronic hepatitis60-80%

acute hepatitis

20%

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

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

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

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

Markers of viral hepatitisMarker 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• 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

High Moderate Low/NotDetectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweat

tearsbreastmilk

Concentration of Hep B virus in Body Fluids

Blood Transfusion Risk

• Hep B: 1/66,000 units of blood

• Hep C: 1/103,000 units of blood

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 ProphylaxisHep 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

Source: CDC

Source: CDC

Hepatitis B vaccine schedule

• 1st dose in ED or UC

• 2nd dose: 1-2 months

• 3rd dose: 4-6 months

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

• 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

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• 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• 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

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

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• 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

– 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• 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

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

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

• 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 AbscessClinical• 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

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

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

Prognosis• Good in uncomplicated cases (<1%

mortality)

• Bad if pulmonary complications (20% mortality)

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• 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