99 TOPICS TEACHING ROUNDS

SABRINA SQUIRE, PGY2 FMSEPT 8 , 2015

Viral Hepatitis

Objectives

In a patient presenting with hepatitis symptoms and/or abnormal liver function tests, take a focused history to assist in establishing the etiology (e.g.,new drugs, alcohol, blood or body fluid exposure, viral hepatitis).

  In a patient with abnormal liver enzyme tests interpret the results to distinguish between obstructive and

hepatocellular causes for hepatitis as the subsequent investigation differs.  In a patient where an obstructive pattern has been identified, Promptly arrange for imaging, Refer for more

definitive management in a timely manner.  In patients positive for Hepatitis B and/or C, Assess their infectiousness, Determine human immunodeficiency

virus status.  In patients who are Hepatitis C antibody positive determine those patients who are chronically infected with

Hepatitis C, because they are at greater risk for cirrhosis and hepatocellular cancer.  In patients who are chronically infected with Hepatitis C, refer for further assessment and possible treatment.

In patients who are at risk for Hepatitis B and/or Hepatitis C exposure, Counsel about harm reduction strategies, risk of other blood borne diseases, Vaccinate accordingly.

  Offer post exposure prophylaxis to patients who are exposed or possibly exposed to Hepatitis A or B.  Periodically look for complications (e.g., cirrhosis, hepatocellular cancer) in patients with chronic viral hepatitis,

especially hepatitis C infection.

I N A PAT I E N T P R E S E N T I N G W I T H HEPATITIS SYMPTOMS A N D / O R ABNORMAL LIVER

FUNCTION TESTS , TA K E A FOCUSED HISTORY T O A SS I S T I N E S TA B L I S H I N G T H E

ETIOLOGY ( E . G. , N E W D R U G S, A L C O H O L , B L O O D O R B O D Y F LU I D E X P O S U R E , V I R A L

H E PAT I T I S ) .

Objective 1

Symptoms

AsymptomaticFeverMalaiseAnorexiaNausea/vomitingJaundiceAbdominal painDark urinePale, clay coloured stools

HISTORY

Identify potential risk factors for liver disease

Exposures Alcohol Drug use (identify/quantify all prescription,

herbals and illicit) Occupational/recreational (mushroom picking,

industrial vinyl choride) Risk for viral hepatitis

A = fecal/oral, close contact (household, sexual, daycares), blood exposure (rare)

B = parenteral, sexual, household, vertical C = parenteral (IVDU, tattoo), endemic (Pakistan,

Egypt), blood transfusion before 1992, higher risk sexual activities, vertical

Other disorders associated with liver disease AutoAbs (autoimmune) Tox screen (hepatotoxins) Right sided HF (congestive hepatopathy) Obesity, DM, hyperlipidemia (NAFLD) Systemic disease (hemochromatosis, a1

antitrypsin, wilson’s) Pregnancy (gallstones) IBD (Primary sclerosing cholangitis)

PHYSICAL EXAM

Look for clues to etiology and signs of chronic liver disease

Temporal and proximal muscle wasting Jaundice, icterus Spider nevi Palmar erythema Gynecomastia Caput medusa Hepatic encephalopathy Asterixis Advanced etoh cirrhosis: Dupuytren’s contractures,

parotid enlargement, testicular atrophy Abdominal malignancy: enlarged left supraclavicular

node (Virchow’s node) or periumbilical nodule Hepatic congestion: increased JVP Right sided pleural effusion Ascites (fluid wave, shifting dullness, bulging flanks) Palpable spleen Liver exam:

Grossly enlarged, nodular or obvious mass = malignancy Tender – viral or alcoholic hepatitis + Murphy’s: cholecystitis or ascending cholangitis

EnzymesElevation = damage to liver or biliary obstruction

Serum aminotransferases Alanine aminotransferase

(ALT) Aspartate aminotransferase

(AST)Alkaline phosphatase

(ALP)Gamma-glutamyl

transpeptidase (GGT)Lactate Dehydrogenase

(LDH)

AlbuminProthrombin

time/International normalized ratio (INR)

Bilirubin

Liver Biochemical and Function Tests

FunctionAbnormalities = impaired synthetic function

IN A PATIENT WITH ABNORMAL L IVER ENZYME TESTS I NTERPRET THE RESULTS TO

DISTINGUISH BETWEEN OBSTRUCTIVE AND HEPATOCELLULAR CAUSES FOR

HEPATITIS AS THE SUBSEQUENT INVESTI GATION DIFFERS

Objective 2

Hepatocellular pattern Cholestatic pattern

AST&ALT vs ALP+/- Bilirubin+/- Abnormal

synthetic function

ALP vs AST&ALT+/- Bilirubin+/- Abnormal

synthetic function

Etiology

IN A PATIENT WHERE AN OBSTRUCTIVE PATTERN HAS BEEN IDENTI FI ED, PROMPTLY ARRANGE FOR IMAGING , REFER FOR MORE

DEFINITIVE MANAGEMENT IN A T IMELY MANNER.

Objective 3

Cholestasis

Ultrasonography Ddx: extrahepatic cholestasis:

Choledochololithiasis Malignant obstruction (pancreas, GB, ampulla, bile duct

cancer) PSC Chronic pancreatitis w/ stricturing of distal bile duct AIDS cholangiopathy

ERCP Confirm Dx and facilitate biliary drainage Consider MRCP in chronic or high risk for ERCP

Hepatocellular Pattern

Viral hepatitis serologies IgM & IgG anti-hepatitis A Hepatitis B surface antigen/antibody and anti-

hepatitis B core Anti-hepatitis C antibody and hepatitis C RNA

Other: CMV, EBV, HSV, VZV

IN PATIENTS POSITIVE FOR HEPATITIS B AND/OR C , ASSESS THEIR

INFECTIOUSNESS , DETERMINE HUMAN IMMUNODEFICIENCY VIRUS STATUS.

Objective 4

IN PATIENTS WHO ARE HEPATI T I S C ANTI B ODY POSIT I VE DETERMINE THOSE

PATIENTS WHO ARE CHRONICALLY INFECTED WITH HEPATITIS C , BECAUSE

THEY ARE AT GREATER RISK FOR CIRRHOSIS AND HEPATOCELLULAR CANCER.

Objective 5

Serology Interpretation – Hepatitis B

Surface Antigen(HBsAg)

Surface Antibody(anti-HBs)

Core Antibody(anti-HBc)

Interpretation

- - - Susceptible

- + - Immunity by Vaccination

- + + Immunity by natural infection

+ - +IgM antiHBc

+

Acute infection

+ - +IgM antiHBc

-

ChronicInfection

- - + 4 possibilities-Recovering acute-Distant immunity-Susceptible w/ FP

core-Chronic infxn w/

undetectible Ag

Serology Interpretation – Hepatitis C

Anti-HCV Non-reactive: no further action

If recent exposure: test HCV RNA Reactive: presumptive HCV infection

HCV PCR and genotype Detected: Current HCV infection Not detected: no current HCV infection

Chronic infection 70-90% develop chronic infection Fluctuating or persistently elevated liver enzymes (>6m) 5-20% develop cirrhosis 1-5% develop HCC

IN PATIENTS WHO ARE CHRONICALLY INFECTED WITH HEPATITIS C , REFER FOR

FURTHER ASSESSMENT AND POSSIBLE TREATMENT

Objective 5

HCV Treatment

Indications All patients with chronic hepatitis C who have compensated liver

disease, are willing to undergo therapy and have no contraindications, should be considered candidates for antiviral treatment. Absolute: Pregnancy Strong: Etoh abuse, hepatic decompensation, CAD, solid organ transplant Relative: major depression, major psychosis, autoimmune, renal failure No longer CI: Normal ALT, IVDU, stable methadone maintenance,

neutropenia, anemia, TCP, controlled seizure disorder, >65yo, etoh use

Current PEG-Interferon + Ribavirin Primary objective is complete viral elimination (sustained

virological response) Success and duration of treatment depends on genotype

IN PATIENTS WHO ARE AT RISK FOR HEPATI T I S B AND/OR HEPATIT I S C

EXPOSURE, COUNSEL AB OUT HARM REDUCTION STRATEGIES , R ISK OF OTHER

BLOOD B ORNE DISEASES, VACCINATE ACCORDINGLY.

Objective 6

Prevention and Risk-Reduction

Vaccinations – avoid further hepatic insults Havrix (o,1,6m) HepB Vaccine (0,1,6m) Consider Pneumovax, Influenza

Harm reduction Safe injection sites, crack pipe exchange Safe sex practices (increased progression with co-

infection HDV, HIV)

OFFER POST EXPOSURE PROPHYLAXIS TO PATIENTS WHO ARE EXPOSED OR POSSI BLY

EXPOSED TO HEPATIT IS A OR B .

Objective 7

Hepatitis A Hepatitis B

Ig within 14 daysRoutinely to household

and intimate contactsSelected situations in

institutions or with common source exposure (food prepared by infected food handler)

Vaccination

Ig within 48hVaccination

Post-exposure Prophylaxis

PERIODICALLY LOOK FOR COMPLICATIONS (E .G. , C IRRHOSI S, HEPATOCELLULAR

CANCER) IN PATIENTS WITH CHRONI C V IRAL HEPATI T I S, ESPECI ALLY HEPATIT IS C

INFECTION.

Objective 8

Surveillance

Liver fibrosis Clinical exam Ultrasound

Nodular shrunken liver, splenomegaly or portal hypertensive collaterals

FibroScan measures liver stiffness as a surrogate for fibrosis Traditionally, liver biopsy

Staging fibrosis Serum Markers:

Routine biochem (AST, ALT, platelets) Indirect markers (a-2 macroglobulin and haptoglobin) Direct markers (hyaluronic acid and tissue inhibitor of matrix

metalloproteinase 1)

Hepatocellular Carcinoma Screening at 6-month intervals with ultrasound + AFP

References

Family Medicine Notes: Preparing for the CCFP Exam 2014

UptoDateOverview of Viral Hepatitis Lecture by Dr. Curtis CooperPocket Medicine Fourth EditionCDC WebsiteMultidisciplinary Canadian consensus recommendations

for the management and treatment of hepatocellular carcinoma, Curr Onc 2011

An update on the management of chronic hepatitis C: Consensus guidelines from the Canadian Association for the Study of the Liver, Can J Gastroenterology 2012