| What is viral hepatitis? | It is an inflammation of liver caused by a hep virus.
All hep viruses can cause acute disease, only HBV and HCV can cause chronic infection.
Chronic infection can develop into cirrhosis and hepatocellular carcinoma,, and they remain infectious and may transmit the disease for many years
Infrequent cases of viral heptatitis include adenovirus, CMV, EBV, HSV, other pathogens |
| What are the types of viral hepatitis? | Self-limited: short duration with no carrier state
Chronic persistent hepatitis: Persists without symptoms
Chronic active hepatitis: causes necrosis, fibrosis, cirrhosis and liver failure, may include an asymptomatic period. |
| What is acute viral hepatitis? | may be subclinical to self-limited to fulminant, may progress to acute liver failure marked by poor synthetic function INR 1.5 in absence of other liver disease and hepatic encephalopathy (which is fulminant hepatic failure, attributed to increased permeability of BBB resulting in brain edema, occurs in hepA or B, HepE in asia, HepC controversial)
FHF may resolve but in more than half of cases cause death
Acute viral hepatitis may evolve to chronic one |
| How is the progression of liver disease? | Starts with fibrosis (after inflammation, liver repairs itself and scarring occurs)
Cirrhosis (scars join together, nodules form, blood flow blocked, liver shrinks and becomes hard)
Liver failure (Severe cirrhosis, unable to filter wastes toxins and drugs, and doesn't produce clotting factors) |
| How is the history of presentation of viral hepatitis? | It varies with the individuals and the causative viral agent.
Some are asymptomatic, some are mildly symptomatic at presentation, and others rapidly get FHF
Classically 4 phases, phase I is replication phase (asymptomatic, labs see markers of hepatitis)
Phase II is prodromal phase (nausea, anorexia, alteration in taste, arthralgia, pruritis, aversion to cigarette, dx as gastroenteritis or viral illness)
Phase III is Icteric phase (dark urine, GI symptoms and malaise, RUQ pain with hepatomegaly)
and phase IV is convalescent phase (resolve symptoms and icterus and enzymes) |
| What are the physical exam findings in viral hepatitis? | Low grade fever, vomiting, anorexia, dehydration, icterus, jaundiced skin/ rashes, tender enlarged liver |
| What are the complications associated with viral hepatitis? | Acute or subacute hepatic necrosis, chronic active hepatitis, cirrhosis, hepatic failure, hepatocellular carcinoma in pt with HBV or HCV |
| What are the differential diagnoses in case of hepatitis? | Liver abscesses, drug-induced hepatitis, autoimmune hepatitis, hepatocellular carcinoma, pancreatic cancer. |
| What are the approach considerations in case of hepatitis? | Some benifit from pharmaco (chronic HBV/HCV)
most are outpatients (hydration, followup, refrain from hepatotoxins, avoid physical exertion)
No specific emergency measures except IV and supportive care.
Pt admitted to hospital if severe complications are present, if encephalopathic evaluate it (personality change, sleep-wake cycle...)
Other labs for evaluation (PT >3s, Bi>30, hypoglycemia, comorbidity, immunocomprimised, old age) |
| What is hepA? | Vaccine-preventable liver infection, found in stool and blood of infected people, very contagious, spreads through close contact and feco-oral (highest in stool in IP) |
| How is the presentation of HepA in general? | Symptoms can last up to 2 months, include fatigue, nausea, stomach pain and jaundice, mostly not long lasting, best way to prevent is vaccination or getting infected in young age where it still is harmless. |
| What are the clinical criteria of HepA? | Clinical criteria include: acute illness (hepatitis), jaundice and elevated Bi>3 or ALT>200, absence of a more likely diagnosis |
| What are the lab criteria of diagnosis of HepA? | IgM + (anti-HAV), or PCR + for HAV |
| What are the case classifications of a confirmed HepA? | Case meeting clinical criteria and IgM +, or HepA PCR +, or meets clinical criteria in contact with a confirmed case of HepA within 15-30 days prior to onset of symptoms. |
| How is the evolution of levels of Igs and HAV in feces and blood? | Viremia occurs after 1-2 weeks of exposure, persists through a period of elevated liver enzymes (ALT).
Humoral response occurs prior to symptom onset, IgM detectable before symptoms in about 3-6 months and then decline, and as soon as IgM decline IgG persist after 1 year of exposure to stay lifelong. |
| How is HepA transmitted? | Feco-oral, sexual contact, close contact.
Blood bourne transmission is very uncommon.
Oral entry, crosses intestine to blood stream, then to parenchyma of liver then to bile and finally excreted to stool. |
| Who are pt at risk of acquiring HepA? | People with increased risk of acquisition:
travelers, gay men, IV drug users, healthcare, homeless, people interacting with travelers.
People at risk of severe HAV:
chronic liver disease pt, immunodeficient pt.
highest in developing countries, areas of low socio economic status, areas without sufficient sanitation |
| What are the signs and symptoms of HepA? | Fever, fatigue, anorexia, nausea, abdominal pain, dark urine, clay stool, jaundice, joint pain
(most infections in children are asymptomatic, and if symptomatic no jaundice.
Last less than 2 months, and may relapse up to 6 months
IP is 28 days average (between 15-50 days)
Can live in environment for months |
| How is HepA virus killed? | Temperature >85 C for 1 min (can still spread in cooked food)
Freezing has no effect
Adequate chlorination of water kills it, transmission through contaminated water is rare |
| Can hepA become chronic? Can reinfection occur? | NO and NO (due to IgGs) |
| How is HAV infection prevented? | Vaccination (full two-dose series)
Igs (short term protection after exposure and pre exposure, within 2 weeks after exposure max)
Good hygiene |
| Who should be vaccinated for HAV? | Children (age 12-24 months, unvaccinated between 2-18 years)
People at risk of getting it, and severe risk
Pregnant women at risk
In case of outbreak.
In addition to it a GamaSTAN S/D Ig is recommended coadministered. |
| What is hepB? | Vaccine-preventable liver infection, spread by blood, sex and IV drug users and from mother to baby at birth
Not all people are symptomatic, but ones with symptoms have fatigue, anorexia, pain, nausea and jaundice |
| What is the duration of a hepB infection? | For many it is short-term illness, but can become chronic that can lead to cirrhosis or liver cancer.
Risk of chronicity is related to age, 90% of infants with HepB go chronic (leads to cirrhosis and maybe hepatocellular carcinoma or decompensated liver), for adults only 2-6% become chronic (1% FHF, others go inactive state but may develop into progressive chronic hepatitis and then into cirrhosis.
Best prevention is vaccine |
| How is the epidemiology of HepB? | It is a global pandemic, 350 million cases, one million annual deaths, and can be prevented by vaccination
Infection occurs for 2 billion worldwide, and 350 million are chronic, and 20% die of cirrhosis or cancer.
Lowest prevalence is in high standard countries where vaccination and hygiene is important |
| Give an overview of HBV? | Hepadnavirus, dsDNA, incomplete positive strand ,complete negative strand has 4 overlapping genes
S; HBsAg (viral surface peptide)
C: HBcAg (nucleocapsid) and HBeAg (unknown)
P: polymerase RT
X: X protein transcription regulation activity |
| What are the indications of each of the Ag of HBV? | S: antigen indicating infection
DNA: indicates active infection
ALT: increases in case of liver injury
anti-HBc: (core antibodies) at the onset of symptoms and stay for life (previous or ongoing infection)
anti-HBs: indicates immunity
HBeAg: correlates with replication but not very detectable |
| What are the stages of serological testing in HBV infection? | 3 stages:
Infection: HBsAg detected early (weeks before symptoms), anti-HBc is first Ab to appear, anti-HBe appears to reduce infectivity
Replication: active viral load, increased HBeAg and HBV DNA
Disease activity: increased ALT |
| What are the case definitions of HBV infection? | Acute HepB, Chronic HepB, Perinatal HepB. |
| How is the clinical description of acute hepB? | acute illness with discrete onset of any hepatitis symptoms (fever, headache, nausea, anorexia, abdominal pain, jaundice or increased ALT >100)
Or a negative HBsAg prior to a positive one 6 months later |
| How is the clinical description of chronic hepB? | No symptoms required, maybe no evident liver pathology, or a spectrum to liver cirrhosis or cancer
Labs for dx: IgM anti-HBc negative and positive HBs or HBe or DNA / HbeAg positive 2 times 6 months apart |
| How is the case classification of chronic HepB? | A single HBeAg or DNA only positive or HBsAg positive only and isn't acute HepB is confirmed with chronic HepB |
| How is the clinical description of perinatal HepB? | child <2 year old, from asymptomatic to FHF
Labs (one or more): positive HBsAg (at least 4 weeks after last dose of vaccine)
positive HBeAg
detectable HBV DNA |
| How is the case classification of perinatal HepB? | Probable: positive HBsAg >1 month, or positive HBeAg/DNA >9 months and mother unknown
Confirmed: child borne to infected mother and positive HBsAg >1 month, or positive HBeAg or DNA >9 months |
| How should we manage perinatal HBV? | Infant of infected mothers should receive HBIg and first dose of vaccine within 12 hours of birth, second dose at 1 month and third at 6 months
After completion of vaccine, see HBsAg and antibody 1 months after |
| How is the natural history of HBV infection? | Immune tolerance state: HBeAg positive, DNA positive, HBsAg positive with no antibodies
Immune clearance: decline in DNA, HBs decreases, ALT high, HBe is becoming more negative and antibodies are forming.
Inactive state: Undetectable DNA, anti-HBe positve, HBeAg and HBsAg negative
It is all associated with HBeAg level. |
| How is the pathophysiology of HepB? | chronic: 10-30% are symptomatic (fatigue most common)
Acute flares (similar to acute hep), extrahepatic manifestations (polyarteritis nodosa, cyroglobulinemia and glomerulonephritis)
May have abnormal liver chemistry levels, inflammatory liver biopsy
May be HBeAg positive or negative
If positive (active replication, DNA >2 x104
if negative (precore mutation, HBeAg not produced) |
| What are the factors influencing natural history of HepB? | Viral load HBV, gender, age, host immune system, co-infection with HCV or HIV, alcohol use, HBeAg status, viral mutations |
| How is HBV transmitted? | Sex, injection, birth, blood contact, exposure to needles, sharing of any item that breaks through skin and mucosa
Highest concentration of HBV is in serum, moderate is in semen/vaginal fluid/saliva , low in urine and feces. |
| Talk about perinatal transmission of HBV? | One of the major modes of transmission, may occur intrapartum or utero
Neonates infected are usually asymptomatic, greatest risk is for HBeAg positive women (6 months risk of infection is 70%, 90% develop chronic infection. |
| Talk about other modes of transmission of HBV. | More easily in HIV pt, oral or genital sex, but not through kissing and close contact
Parenteral: IV drug users, more in pt with hemophilia, renal dialysis, organ transplantation
Sporadic cases: unknown cause, 27% of cases. |
| How long does HBV survive outside the body? | Remains for 7 days, should be disinfected by bleach 1:10 dilution + wear gloves |
| Who should be screened for HBV? | People in endemic countries (>2% prevalence), men sex men, IV drug user, HIV pt, history of household infection, immunocompromised pt, renal dialysis pt, blood donors, elevated ALT people, pregnant. |
| What are the age preferences of symptoms of HBV? | <5 years mostly are asymptomatic, 30-50% above age 5 have symptoms
Disease is more severe if >60 years
25% chronic, 15% of them die premauterly from liver cancer or cirrhosis and most stay asymptomatic till inset of cirrhosis. |
| How is the interpretation of HBV serology? | HBsAg: infectious.
anti-HBs: recovery and immunity
anti-HBc: previous or ongoing infection
IgM anti-HBc: positive recent infection
So vaccine give + anti-HBs but not anti-HBc |
| How long after exposure to HBV can HBsAg be detected? | 4 weeks average after exposure, no longer infectious after 7 weeks of onset of symptoms, and 15 weeks after symptoms HBsAg becomes negative (if not chronic) |
| How is HepB reactivation occur? | Sudden rise in DNA with inactive chronic infection, accompanied with acute flares with elevations of liver enzymes with or without symptoms, can be severe and lead to death
risk is for chemo pt, immunosuppressed, HIV, bone marrow transplant, HCV coinfection |
| How is HBV infection treated? | Acute: supportive treatment
chronic: antivirals and monitor liver damage |
| What is HBV superinfection? | preceded by HDV infection leads to acute liver failure |
| Talk about HepB vaccination. | Every one should be vaccinated, adults above 60 with no risk of HepB may not receive a vaccination.
Schedule is 3 IM injections, second dose 1 month and third 6 months after the first dose
Any pt with allergy to prior dose of hepB doesn't receive it
or any contraindication of other coadministered vaccines |
