Viral Hepatitis

• Orofecal: A, B (possible)
• Sexual: A, B, C (rare)
• Blood: A (rare), B, C

A: travelers to regions with high rates of Hep A, sex contacts, MSM, household members or caregivers of infected person, illegal drug users (injection and non injection), pt with clotting factor disorders

B: infants of infected mothers, sex partners (or those with multiple partners or MSM), those with STDs, IVDUs, household contacts of infected person, healthcare workers exposed to blood on the job, hemodialysis patients, residents and staff of facilities for developmentally disabled persons, travelers to endemic regions

C: Current or former IVDUs, recipients of clotting factors prior to 1987 or of blood transfusions or organ donations before 1992, long-term hemodialysis pts, persons with known exposures to HCV, HIV pts, infants of infected mothers

• Asymptomatic - Rise in LFTs and serologic markers present
• Symptomatic - 4 phases - 1. incubation period, 2. pericteric phase, 3. icteric phase, 4. convalescent phase
• Fulminant - severe liver failure that develops w/in 8 weeks of sx onset. Liver cell destruction leading to coagulopathy and hepatic encephalopathy

• 1. incubation period - time from infx to onset of sx
• 2. pericteric phase - lasts days to 3 weeks - nonspecific influenza like sx - malaise, aches, fever - conjugated bilirubin rises, dark urine
• 3. icteric phase - lasts 7-30 d - jaundice in sclera, pale stools, pruritis reported in 40% of pts
• 4. convalescent phase - may take up to 6 mo - fatigue and weakness

• A: 28 d
• B: 120 d
• C: 45 d

• hepatocellular necrosis and inflammation, often with fibrosis, lasting 6+ months
• not caused by HAV
• mild to severe
• can result in cirrhosis, portal HTN, hepatocellular carcinoma
• liver injury is d/t cytolytic t-cell response to virus-infected hepatocytes (not from the virus itself being cytopathic)

• Enterally - A, E (not in chronic carrier state)
• Parenterally - B, C, D (exist in chronic carrier state)

• HBc (core particle) - indicates replicating HBV
• HBsAg (surface antigen) - the immunogenic component of the vaccine

If pt is negative for HBsAg, anti-HBc, and anti-HBs they are susceptible

If pt is negative for HBsAg, but positive for anti-HBc and anti-HBs, they are immune d/t natural infection (have cleared the infx)

If pt is negative for HBsAg and anti-HBc, but positive for anti-HBs, they're immune d/t HBV vaccine

If pt is positive for HBsAg, anti-HBc, IgM anti-HBc, and negative for anti-HBs, they are acutely infected (can tell b/c IgM goes up first)

If pt is positive for HBsAg and anti-HBc, and negative for IgM anti-HBc and anti-HBs, they are chronically infected

If the HBsAg is negative, the anti-HBc is positive, and the anti-HBs is negative, the interpretation is unclear. Most likely a resolved infection, but could be susceptible, low level chronic infx, or resolving acute infx.

• Defined as presence of detectable HBsAg, HBeAg, and HBV DNA for > 6 months.
• The HBsAg peaks around 2 weeks post exposure and then levels out and stays high.
• The total anti-HBc and IgM anti-HBc begin to rise around 6 weeks and peak around 16 weeks. The IgM then drops off while the total anti-HBc remains high and levels off.

Immune tolerant (4-10 weeks) - viral replication is active, but little or no evidence of disease. HBsAg are produced and IgM anti-HBc are produced before sx onset

Immune active - symptomatic - flares of hepatitis and increased ALT. Presence of HBeAg. Development of cirrhosis and hepatocellular carcinoma occurs in this phase. Repetitive cycle of inflammation, damage, healing, inflammation, damage, healing, etc.

Inactive carrier - levels of HBV DNA are present in liver, but undetectable. Seroconversion - anti-HBe develop and clear HBeAg.

• No drugs therapies
• Supportive tx only - bed rest, anti-nausea meds (avoid chlorpromazine d/t cholestasis), correct fluid imbalance, pain control with APAP, cholestyramine for pruritis

• Acute - just supportive tx
• Chronic - interferons, lamivudine, adefovir, entecavir, tenofovir, telbivudine
• Only interferons have a defined duration of teatment - the rest are for at least 6 months after appearance of anti-HBe

• infants born to infected mothers
• decompensated cirrhosis
• compensated cirrhosis
• cirrhosis or advanced fibrosis and HBV in serum
• reactivation following immunosuppression
• acute liver failure

• acites
• hepatic encephalopathy
• hemorrhage d/t portal HTN

• Bilirubin </= 2
• Albumin stable and WNL
• PTT < 3 sec (prolonged)
• WBC >/= 3,000
• Platelets >/= 70,000

• compensated
• cannot use interferons if decompensated d/t incr risk of liver failure

• goal = complete resolution of s/s and eradication of HCV
• tx indicated for previously untreated pts with chronic HCV, circulating HCV DNA, increased ALT, and histologic evidence of moderate to severe hepatitis and fibrosis

• fever
• fatigue
• loss of appetite
• nausea
• vomiting
• abdominal pain
• clay-colored stool
• joint pain
• jaundice

• inhibit viral replication and cell proliferation
• immunomodulation

alone or in combo with ribavirin for chronic HCV

• alone or in combo with ribavirin for chronic HCV
• chronic HBV with compensated liver disease

• alone or in combo with ribavirin for chronic HCV in pts > 3 years with compensated liver disease
• chronic HBV in pts > 1 year with compensated liver disease

Depression, flu-like sx, insomnia, bone marrow suppression - neutropenia, irritability, alopecia

• nucleoside analogue inhibits reverse transcriptase of HBV
• indicated for treatment of chronic HBV
• AEs - lactic acidosis and severe hepatomegaly with steatosis, malaise, fatigue, GI

Resistance may develop

• lamivudine
• adefovir
• entecavir
• tenofovir
• telbivudine
• They inhibit reverse transcriptase of HBV

lactic acidosis and severe hepatomegaly with steatosis

• nucleoside analogue - MOA vs. HCV unknown
• indicated in combo with peginterferon alpha2a or alpha2b to treat chronic HCV infx
• AE - hemolytic anemia within 1-2 weeks of initiation of tx
• Pregnancy category X

• peginterferon-alpha2b: 1mcg/kg/wk x 52 wk
• peginterferon-alpha2a: 180mcg/wk SQ x 48 wk
• interferon-alpha2b: for HBV, 30-35 million IU SQ TIW; for HCV, 3 million IU SQ TIW
• Lamivudine: 100 mg PO QD
• Adefovir: 10 mg PO QD
• Entecavir: 0.5 - 1 mg PO QD (depend on if tx naive or not)
• Tenofovir: 300 mg PO QD
• Telbivudine: 600 mg PO QD
• Ribavirin: genotypes 2,3 give 800 mg po qd; genotypes 1,4 give 1000 mg po qd if , 75 kg or 1200 mg po qd if 75 kg +