Viral Hepatitis: A C E
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Transcript of Viral Hepatitis: A C E
Viral Hepatitis:A C E
Hepatitis: inflammation of liver; presence of inflammatory cells in organ tissue
Acute Viral Hepatitis: symptoms last less than 6 months Acute Hepatic Failure: Massive hepatic necrosis with
impaired consciousness within 8 wks of onset of illness. Chronic Hepatitis: Inflammation of liver for at least 6
months Cirrhosis: Replacement of liver tissue fibrosis, scar
tissue Fulminant Hepatitis: severe impairment of hepatic
functions or severe necrosis of hepatocytes in the absence of preexisting liver disease
Clinical Terms
PathophysiologyTargets of the Hep viruses are hepatocytes: Hepatocyte uptake involves a receptor on the
plasma membrane of the cell After entry into the cell, viral RNA is uncoated, and
host ribosomes bind to form polysomes. Viral proteins are synthesized, and the viral genome is copied by a viral RNA polymerase
Minimal cellular morphologic changes result from hepatocyte infection
Lymphocytic infiltrate; varying degree of necrosis.
Classic presentation:infectious hepatitis
Phase 1 - Viral replication; Patients are asymptomatic during this phase.
Phase 2 – Prodromal Phase 3 - Icteric phase Phase 4 - Convalescent phase;
symptoms and icterus resolve. Liver enzymes return to normal.
Clinical Evaluation: Acute Viral Hepatitis
1. Prodromal phase: Patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias,
malaise, fatigue, urticaria, and pruritus. Some develop an aversion to cigarette smoke.
When seen by a health care provider during this phase, patients are often diagnosed as having gastroenteritis or a viral syndrome.
2. Icteric Phase Jaundice, Patients may note dark urine, followed by pale-colored stools. In addition to the predominant gastrointestinal symptoms and malaise, patients
become icteric and may develop right upper quadrant pain with hepatomegaly.
Severe cases may result in Fulminant Hepatitis:1.Hepatic Encephalopathy: B/L asterixis, palmar erythema2.Hepatorenal syndrome3.Bleeding diathesis
Clinical Evaluation: Chronic Hepatitis
- Occurs after acute Hepatitis in >80% of people with HCV
- Some are asymptomatic, or have mild symptoms; others may only present with late complications (cirrhosis/HCC)
- Categorized based on grade of inflammation, stage of fibrosis, and etiology of disease
Physical Exam Low-grade fever.
Significant vomiting and anorexia dehydration such as tachycardia, dry mucous membranes, loss of skin turgor, and delayed capillary refill.
Icteric phase: icterus of the sclerae or mucous membranes or discoloration of the tympanic membranes.
The skin may be jaundiced and may reveal urticarial rashes. Liver may be tender and diffusely enlarged with a firm, sharp,
smooth edge.
Imaging Studies No specific imaging studies needed for diagnosis Obtain the appropriate diagnostic imaging studies (eg, ultrasound, CT) if
the differential diagnosis favors gallbladder disease, biliary obstruction, or liver abscess.
Liver biopsy usually in cases of: o The diagnosis is uncertain. o Other coinfections or disease may be present. o The patient is immunocompromised. o Asses severity of chronic hepatitis B or chronic hepatitis C.
Histologic FindingsLymphocytic infiltration, moderate degrees of inflammation and necrosis,
and portal or bridging fibrosis are noted. Regenerative nodules are seen in patients with cirrhosis.
Lymphocytes surround apoptotic hepatocytes
Clustered hepatocytes with ballooning degeneration (clear vacuolated cytoplasm)
•LFT: Elevation of serum transaminases not diagnostic, but usefula)ALT elevated more than ASTb)Acute Hepatitis: ALT > 1000c)Chronic HCV: ALT is generally lower than 1000
* Urine analysis: presence of bilirubin. * Serum bilirubin: Total bilirubin may be elevated in infectious hepatitis. Bilirubin levels higher than 30 mg/dL indicate more severe disease. * Alkaline phosphatase: if elevated significantly, consider abscess or biliary obstruction. * Prothrombin time (PT) if prolonged impaired synthetic function of the liver. * BUN & serum creatinine decreased renal function suggests fulminant hepatic disease. * Serum ammonia in patients with AMS or other evidence of hepatic encephalopathy.* CBC: lymphocytosis
Lab Studies:
Differentials:Abdominal Trauma, Blunt
Obstruction, Small BowelAneurysm, Abdominal
PancreatitisCholangitis
Pediatrics, GastroenteritisCholecystitis and Biliary Colic
Pediatrics, IntussusceptionCholelithiasis
Gastritis and PUDGastroenteritis
Hepatitis A Common cause of acute hepatitis Single-stranded, positive-sense, linear RNA enterovirus
(Picornaviridae) Transmission fecal-oral route; Contaminated water and food The incubation period of hepatitis A virus is 2-7 weeks, AST & ALT levels usually return to reference ranges over 5-20
weeks. High risk Travellers: vaccinations; passive immunoglobins
given to those exposed Mild self-limited disease and confers lifelong immunity to hepatitis
A virus. Chronic infection with hepatitis A virus does not occur. Treatment: supportive
Diagnosis: HAV **Serum Serology: presence of serum
antigens and immunoglobins HAV: IgM anti-HAV: positive at the time of
onset of symptoms; results remain positive for 3-6 months after the primary infection
Anti-HAV IgG appears soon after IgM and generally persists for many years.
Hepatitis C Spherical, enveloped, single-stranded RNA virus
(Flavivirus genus) Incubation period: 7-8 wks 170 million infected worldwide Major cause of chronic hepatitis in U.S. More common in Hispanic, AA population;
females have better outcome Parenteral Transmission: IV drug users Most common indication for liver transplantation
Hepatitis C Usually clinically mild, does not cause significant
acute illness Fluctuating elevations of AST & ALT 20% likelihood of developing cirrhosis 50% likelihood of developing chronic hepatitis Incubation period: 15-150 days, with symptoms
developing anywhere from 5-12 weeks after exposure.
Diagnosis: HCV HCV: Anti-HCV; cannot distinguish acute from chronic infection EIA: antibodies against core protein and nonstructural proteins;
may appear 3 – 5 months after infectionPCR: used to detect viral RNA HCV80% of cases: patients are asymptomatic and do not develop
icterus.Treatment: Interferon alpha, Ribavirin; PEG-IFNs (better sustained
absorption, a slower rate of clearance, and a longer half-life than those of unmodified IFN)
Hepatitis E Hepatitis E virus (HEV) RNA virus of the
genus Hepevirus Enterically transmitted infection; fecal-oral
route, typically self-limited Most outbreaks occur in developing countries. Symptoms of acute hepatitis Incubation period of hepatitis E virus is 2-9
weeks Case fatality rate is 4%
Hepatitis E: diagnosis Serum, liver, and stool samples can be
tested for HEV RNA Anti-HEV antibodies:- IgM (acute)- IgG (chronic)AST & ALT are elevated several days before
the onset of symptoms; return to normal within 1-2 months after the peak severity of disease.
Treatment: supportive
A 61 yo F is brought to the ER, drowsy and disoriented, only able to follow simple commands. On PE, her abdomen is distended and non-tender and she is jaundiced. In her purse, the physician finds prescriptions for peginterferon and ribavirin. When asked to raise her hands, the physician notes a coarse tremor. Lab values show ALT = 93U/L, AST = 89U/L, total bilirubin = 3.1 mg/dL, and ammonia = 124microg/dL. What is the most likely diagnosis?
A. Bleeding esophageal varicesB. Hepatic encephalopathyC. Hepatocellular carcinomaD. Hepatorenal syndromeE. Spontaneous bacterial peritonitis
Hepatitis: B & DRobert Leahy
Hepatitis B(HBV)--EPIDEMIOLOGY HBV is a DNA virus that belongs to the hepadnavirus family.
2 billion people worldwide have past or present infections 400 million people are chronic HBV carriers. Eight genotypes of HBV identified and re-labeled A through H. HBV is the cause of 60% to 80% of worldwide Hepatocellular
Carcinoma(HCC). 500,000 to 1 million deaths worldwide are attributed to it. 5% to 10% of all liver transplants are attributed to HBV.
AT Risk Groups IV drug users People receiving multiple blood transfusions Sexual promiscuity People in contact with HBV carriers Travelers to endemic areas of South
America, Southern Asia, and Africa Resident and employees of residential care
facilities Health Care Workers
PathophysiologyTransmission 3 main ways:
Parenterally/percutaneous route----IV Drug Users, needle sticks, Hemodialysis patients
Sexually
Vertical/ Perinatal route
SerologyHBsAg Present in acute of chronic infection Detectable 1 to 2 weeks after infection
HBeAg Appears shortly after HBsAg Indicates viral Replication and Infectivity
HBsAB(Anti-HBS) Present after vaccination or clearance of HBsAg(Usually 1 to 3
months) Indicates immunity to HBV
Hb core Antibody (IgM anti-Hbc or IgG anti-HBc) Only Serological marker of HBV during "Window Period"
Clinical PresentationAcute Hepatitis B - less than 6 months; Based on significant aminotransferase activity
due to necro inflammatory injury Symptoms are often non-specific symptoms such as myalgia, malaise , nausea,
fatigue , pruritus, abdominal pain, RUQ, jaundice Fulminant Hepatitis--Acute HBV results in Liver Failure
Chronic Hepatitis B - greater than 6 months; Based on grade, stage, and etiology. Fibrosis and Necroinflammatory processes; can last for decades
Immune tolerant--High viral replication, NL liver enzymes, low inflammation and fibrosis. Seen in children or those affected early in life.
Immune active--High Liver enzymes and High HBV DNA and HBeAg, Active Replication
Carrier State with low replication Seroconversion from HBeAg to HBeAB Low HBV levels, NL liver enzymes, Reduced Liver inflammation Low risk for developing of HCC
Clinical Presentation cont.Chronic HbeAg negative HBV DNA high, Liver enzymes high,
No HbeAg Seen in late phase of HBV
Resolution Viral clearance of HBV DNA
Diagnosis Serology
Liver Chemistry tests AST, ALT, ALP, and total Bilirubin
Histology--Immunoperoxidase staining
HBV Viral DNA--Most accurate marker of viral DNA and detected by PCR
Liver Biopsy--to determine grade(Inflammation) and stage(Fibrosis) in chronic Hepatitis
Progression Incubation Period: 30-180 days
Acute HBV Infection: 90% resolve by themselves; less than 1% develop fulminant hepatitic failure
Chronic HBV Infection: 2-10% progress to chronic state 90% in children less than five progress to chronic state Risk of Liver Cirrhosis: 5 year accumulation risk of 8% to
20% 5% to 10% of people progress to HCC with or without
preceding cirrhosis; less than 5% achieve a chronic carrier state
Treatment1) Interferon therapy – First Line
Method of action is the inhibition of viral replication of cells thus assisting the immune system
Interferon alpha: TX: SUB-Q 5 million units q D or 10 million units 3x weekly Sub-Q
Side effects: "Flulike Symptoms", alopecia, rash, diarrhea pINF-alpha(pegylated interferon-alpha): 180ug q weekly SUB-
Q Better Choice than IFN-Alpha--Greater Bioavailability, Longer
half life, Better treatment schedule
Treatment cont.2) Nucleoside Analogues -- Lamivudine, Entecavir, Telbivudine
Method of action is the inhibition of viral reverse transcriptase
Lamivudine Dose : 100 mg PO q daily Good for reducing the risk of progression to hepatic decompensation in patients with cirrhosis or
advanced fibrosis Pregnancy category B--Not teratogenic in animal studies and successful use with pregnant women Problem: High rates of resistant mutations Side effect: lactic acidosis
Entecavir – 1st line 0.5 to 1mg PO very effective; low resistance and greater than 90% HBV DNA clearance rate in HBeAG positive Px's. more effective than lamivudine Side effect: lactic acidosis
Telbivudine Dose: 600mg q daily Worse resistant profile than Entecavir Side effect: lactic acidosis
Treatment cont.3) Nucleotide analogues
Method of action is the inhibition of viral reverse transcriptase Tenovir
Dose: 300mg qd Highly effective with low resistance Well tolerated
Adefovir – 1st line Dose: 10mg daily Resistance less than Tenovir Side effect: nephrotoxicity and lactic acid
Medication Guidelines Optimal treatment duration not yet
defined
Interferon drugs don't have resistance issues unlike the antivirals
When to Treat for Chronic Hepatitis
HBV DNA(copies/ml) ALT Recommendation
<105 Normal No treatment , monitor, considered inactive
>105 Normal No treatment, current tx is limited benefit
>105 Elevated (greater than 2 x ULN)
Oral Agents, not PEG IFN
+ or - and compensated cirrhosis
Normal or elevated Oral Agents, not PEG IFN
+ or - and uncompensated cirrhosis
Normal or elevated Oral agents and refer for treatment
1) HBeAg positive
When to Treat for Chronic Hepatitis2)HBeAG negative
HBV DNA(copies/ml) ALT Recommendation
<104 Normal No tx necessary, inactive carrier
>104 Normal Liver Biopsy , treat if abnormal
>104 Elevated Oral agents or PEG IFN
+ or - w/ compensated cirrhosis
Elevated or normal Oral agents, not PEG IFN
+ or - w/ uncompensated cirrhosis
Elevated or normal Oral agents, not PEG IFN
ProphylaxisHBV Vaccine Indicated for everyone and especially those in high risk groups
IM injection at 0,1,6 months in infants and adults Response greater than 90% after 3rd dose
HBV Pregnant Mothers Give 1st dose of Hip B vaccine and Hip B Immunoglobulin(HBIG) o.5 ml within 12 hours of birth.
2nd dose at 1 month, 3rd at 6 months Recheck at 12 months for active infection 95% lifetime immunity Not Done---leads to 90% chronic HBV Transmitted through birth canal during birth or through umbilical cord.
Others i.e. those receiving a needle stick Should receive 0.04 to 0.7 ml/kg of HBIG and 1st dose vaccine within 48 and no later than a
week.
Transplant
Last resort for those with advanced Liver Disease and HCC due to infection
HEPATITIS DTransmission Only as co-infection with acute HBV or with superinfection in chronic
HBV carrier Requires outer envelope of HBsAG for replication and
transmission Can progress to chronic disease Incubation Period 30to 150 days
Serology Hepatitis D antibody (Anti-HDV)
Indicates HDV superinfection Ab not always present in acute infection---requires repeat testing
HEPATITIS DRisk Factors - Same high risk groups as those for Hip B Prevention - Avoidance of Hip B and/or Hip B vaccine DX - HDV antigen in serum or finding Ab to HDV antigen
Clinical Coinfection-self limited Superinfection-acute HBV carriers present with severe acute hepatitis infection w/
increased risk for HDV infection. Fatality Rate - 2% to 10%
Cirrhosis – None
TX:IFN-alpha
Other Causes of Hepatitis
Alcoholic Hepatitis Drug induced Hepatitis Autoimmune Hepatitis Ischemic Hepatitis
A hepatitis panel is ordered for a 27 year old female as part of a routine workup for abdominal pain. Results of serological testing a negative for HBeAg and HBsAg, but positive for HBsAb and IgG HBcAb. The patient has been exposed to Hep B.
a. Patient has recoveredb. Patient is in acute infective disease statec. Window periodd. Chronically infectede. Patient was never infected
Sources1)The Washington Manual of Medical
Therapeutics
2)Harrison's Principles of Internal Medicine
3)Step up to Medicine