HEPATITS PROFILE

KHO, Jeanne LORENZO, Lara Mae 4-BMT HEPATITIS A PROFILE Picornavirus Transmission: fecal-oral route Benign, self-limited disease Incubation period: 15-49 days - HAV RNA is present in stool and plasma & detectable for average of 18 days after clinical onset Viral shedding (days 14 to 21): the time when viral infectivity is highest 3 Tests for HBV 1. ACute HBV hepatitis: HbsAg, IgM anti-HBc 2. Chronic HBV hepatitis: HbsAg, anti-HBc IgG, anti-HBs igG 3. Monitoring chronic HBV infection: HBs, HBeAg, anti-HBs IgG, anti-HBe IgG and HBV DNA LUA, Gemma

Figure 1.1 Time after exposure to HAV HAAg (incubation to early acute) - Occurs early so it doesnt appear during acute phase -Jaundice may develop Incubation period -HAV RNA replicates -Viral particles can be detected in stool Titers: 1. IgM anti-HAV -Most effective diagnostic determination of acute infection - Accompanies the initial rise in ALT & AST - Develops 2-3 weeks after infection and persists 36 mos. 2. IgG anti HAV - Confirmation of past infection - Develops w/in 1-2 weeks of IgM anti-HAV - Remain positive for life Total anti-HAV - Detection of IgM and IgG antibodies HEPATITIS B PROFILE Hepadnavirus Transmission: perinatal, sexual and parenteral routes Incubation Period: 1 to 6 months

Figure 1.2 Timeline of chronic hepatitis B infection (no late seroconversion)

Figure 1.3 Timeline of acute hepatitis B virus (HBV) infection without progression to chronic phase infection Core Window - gap of about 6 months between the time the titer of HBsAg falls and the titer of anti-HBV immunoglobulin IgG (anti-HBs) rises - titers anti-HBc IgM and IgG rise, indicating acute HBV infection - anti-HBe also rises Titers: 1. HBsAg (Hepatitis B surface antigen) - protein present on the surface of the virus - present in the blood with acute and chronic HBV infections - earliest serologic marker of acute infection - detectable 23 months after infection

- undetectable in the blood during the recovery period IgM Total AntiAnti- primary way of identifying those with chronic infections Interpretation Anti- Anti- HBsAg HBeAg
HBc HBc HBs HBe

2. IgM anti-HBc (Anti-hepatitis B core) - 46 weeks after the appearance of HbsAg - first antibody produced after infection with HBV - used to detect acute infection - rises during window period - accompanied by increases in AST and ALT 3. Total anti-HBc (Anti-hepatitis B core) - IgM and IgG antibodies to hepatitis B core antigen - produced in response to the core antigen - usually persists for life - detect acute and chronic HBV infections 4. Anti-HBs (Hepatitis B surface antibody) - levels in the blood rise during the recovery phase - test is done to determine the need for vaccination - used to detect previous exposure to HBV - acquired from successful vaccination 5. HBeAG (Hepatitis B e-antigen) - protein produced and released into the blood by actively replicating hepatitis B virus - found in the blood only when the HBV virus is actively replicating - often used as a marker of infectivity - used to monitor the effectiveness of treatment - there are some types (strains) of HBV that do not make e-antigen; these are common in the Middle East and Asia 6. Anti-HBe (Anti-hepatitis Be antibody) - produced in response to the hepatitis Be antigen - present along with anti-HBc and anti-HBs in patients that recovered from acute hepatitis B infection - used to monitor the infection and treatment in chronic infection HBV DNA (Hepatitis B DNA) - uses PCR; 200 copies/ml to 2 000 000 copies/ml -primary use is to monitor antiviral therapy in patients with chronic HBV infections
IgM Total AntiAntiInterpretation Anti- Anti- HBsAg HBeAg HBs HBe HBc HBc

Recent, resolving HBV infection Acute HBV infection in core window Active chronic HBV infection Chronic HBV carrier state Resolved

+ +

+ + HBV infection HBV immunity + after vaccination Table 1.1 Interpretations of Patterns of HBV Markers

HEPATITIS C Etiologic agent: Hepatitis C virus (HCV) - RNA virus of the flavivirus group consisting of an icosahedral protein coat - Formerly known as non-A non-B hepatitis - Also called transfusion hepatitis - Consists of two core proteins, E1 and E2; and series of proteins labelled NS1-5 o NS2 transmembrane protein o NS3 contains protease and RNA helicase activities o NS4A and B known as cofactors o NS5A- interferon-resisting protein o NS5B RNA polymerase - Six genotypes (1-6) have been identified further divided into subgroups (e.g. 1a, 1b, 2a, 2b) o 1a- predominates in North America o 1b- predominates in Europe o 4 and 5 are unique to Africa Mode of transmission: - primarily through blood transfusions and transplantation - 60% of new cases occur in injection drug users - Sexual transmission accounts for at least 10% of new cases - Can also be transmitted through accidental needle punctures in healthcare workers, dialysis procedure in patients and rarely, transmission from mother to infant

Incubation period of HBV infection Acute HBV infection

Patient presentation: - Chronic infection with HCV occurs in about 85% of infected individuals - Half of chronically infected individuals will have elevated ALT levels - As the disease progresses, inflammation and liver cell death can lead to fibrosis - 20% of those who have fibrosis will progress to cirrhosis - 1-5% of patients with chronic HCV will progress to hepatocellular carcinoma Immunoassays: - second-generation anti-HCV assay o major diagnostic test for HCV infection o detects presence of antibody antigens at an average of 10-12 weeks after infection - third-generation anti-HCV assay o detects antibody at an average of 7-9 weeks after infection - second-generation RIBA-2 assay o the presence of two or more (out of four) antibodies to HCV antigens is considered a positive result. One antibody is indeterminate. No antibody is negative - primary test for confirming persistence of HCV infection is HCV RNA - WHO developed a standard based on an international unit or IU/mL of serum or plasma
INTERPRETATION

Mode of transmission: - Occurs primarily in injecting drug users and haemophiliacs - 20 million individuals may be infected with HDV Disease: - Coinfection o Infection with both HBV and HDV occurs at about the same time o Infection is more severe o Cause of acute fulminant hepatic failure o Has higher fatality rate then HBV infection alone - Superinfection o HDV occurs in the presence of persistent HBV infection o Progression of disease may be faster Immunoassays: - Major diagnostic test is the presence of antiHDV INTERPRETATION COINFECTION SUPERINFECTION ANTI-HBc IgM Present absent

AntiHCV + + + +

RIBA + + Indete rminat e

HCV RNA + + -

Acute HCV infection Active HCV infection Possible HCV clearance False positive HCV test Requires further study

HEPATITIS E Usually presents as an acute, self-limiting hepatitis without progression to a chronic carrier state clinical presentation of hepatitis E is comparable to hepatitis A Type/Family: non enveloped, SS-RNA Hepeviridae Transmission: Fecal-oral route Progression to Chronic State: No Complications: Fulminant liver failure in pregnant women Incubation period: following exposure to HEV ranges from 3 to 8 weeks Severity: HEV>HAV Symptomatic Hev Infection Common in young adults aged 15-40 years and is uncommon in children Asymptomatic Hev Infection Frequent in children and is anicteric Symptoms/Physical Findings: a. With worsening hepatitis E Jaundice: o Abnormally yellow skin or eyes Bruising of the skin Dark urine Pale skin from anemia

HEPATITIS D Etiologic agent: Hepatitis D virus - RNA virus that can replicate only in the presence of HBsAg - Viral particles have viral RNA inside a shell of HbsAg

Liver enlargement Liver tenderness

HEV RNA

Current hepatitis E infection

b. With severe hepatitis E Blood in the stools Blood in the vomit Confusion Lethargy: o A condition of excessive sleepiness or drowsiness. Dehydration Tests Used To Evaluate Hepatitis E: a. Liver profile: - May show elevated liver enzymes and bilirubin Urine bilirubin and urobilinogen Total and direct serum bilirubin ALT and AST ALP Total protein Albumin b. Complete blood count c. Serology tests: HEV Antibodies Screening: EIA or ELISA tests Confirmatory: o Western blot assays - to detect IgM and IgG anti-HEV in serum o Immunofluorescent antibody blocking assays - to detect antibody to HEV antigen in serum and liver IgM anti-HEV is typically present during the acute infection but rapidly declines in the early recovery period d. Molecular tests: HEV RNA Identified by means of polymerase chain reaction (PCR) immune electron microscopy - to visualize viral particles in faeces Detected in feces of most patients for about 2 weeks after the onset of illness, but may persist longer in some cases Serological/ Molecular Markers: IgM anti-HEV IgG anti-HEV Clinical Significance:

e. Coagulation profile: - Hepatitis can disturb blood clotting prothrombin time Imaging Tests To Evaluate Hepatitis E: a. Ultrasound of the abdomen b. CT scanning of the abdomen c. MRI scan of the abdomen Treatment: No commercially available vaccines exist for the prevention of hepatitis E However, recombinant vaccines and subunit HEV vaccines are currently undergoing clinical trials
VIRUSES WITH UNCERTAIN ASSOCIATION WITH HEPATITIS HEPATITIS G Also known as GB virus type C or GBV-C An eveloped, single-stranded RNA virus Family: Flaviviridae Transmission: o Bloodborne route o Perinatal route o Sexual contact Test Used To Evaluate Hepatitis G: a. Molecular Test Reverse transcription polymerase chain reaction (RT-PCR) methods has been based primarily for the detection of the virus Amplify HVG RNA b. Serologic Test EIA largely used as a research tool TORQUETENOVIRUS (TTV) Also known as transfusion-transmitted virus A single stranded non-eveloped DNA virus Genus: Annellovirus Has a trememdous amount of genetic diversity Transmission: o Parenteral transmission o Fecal-oral route o Respiratory route Test Used To Evaluate TTV: a. Molecular Test Detection of TTV Primarily for research purposes *No validated serological tests to detect antibody to TTV

Current hepatitis E infection Current or past hepatitis E infection