Post on 04-Jun-2020
Acute Hepatitis
Dr Monem Alshok
12/3/2017
Viral Hepatitis
NoneInterferon +Interferon
Ribavirin
IFN
Lamivudine
NONETherapy
NONEHBV vaccineNONEImmune globulin
Recombinan vacc
Immune globulin
Inactivated vacc
Prophylaxis
+++HCCancer
1 – 2%
None
5 – 20 %
Common
0.1 %
Infect 80-90%
Hepatitis –70%
0.1 – 1 %
Neonates 90%
Adults 1-10%
0.1 %
None
Clinical
Fulminant
Progression to
chronicity
Fecal - oral+++
+
++
+++
variable
+
Parenteral +++
Perinatal +++
Sexual ++
Fecal – oralTransmission
AcuteAcute / insidiousInsidiousAcute / insidiousAcuteOnset
6 weeks4 – 12 weeks7 weeks4 – 12 weeks4 weeksIncubation
HEVHDVHCVHBVHAV
HEPATITIS A
RNA Virus
Fecal-oral
Incubation 15-50 days
Anti -Hepatitis A IgM present during acute illness.
TX/Prevention: Vaccine, Immune serum globulin for contacts
Px: Good – doesn’t become chronic rarely fulminant liver failure.
Hepatitis A
RNA virus with 4 genotypes but one serotype.
Fecal-oral route but also sexual (homosexual!), IVDA, and most common in USA international travel.
Incidence has significantly decreased with vaccination.
Hepatitis A
Usually acute self limited rarely fulminant especially if associated with chronic hep C.
Manifestations vary with age, more silent in children.
Incubation period of 30 days followed by abrupt prodromal symptoms then jaundice.
Extrahepatic manifestations : vasculitis, optic neuritis, thrombocytopenia, aplastic anemia, transverse myelitis.
Hepatitis A
IgM anti HAV is the gold standard for diagnosis.
Start at the onset of symptoms and remain positive 4-6 months.
Infected individuals are contagious during incubation and for a week after jaundice appears.
Handwashing is very important !!! As HAV survives for up to 4 hrs on fingertips.
Hepatitis A
Treatment is usually supportive.
Prevention is mainly by good hygiene and vaccination ( travel to high risk areas).
IM Immunoglobulin are available for people allergic to vaccine and immunocompromised, they provide passive immunity for up to 6 months.
HBV infection
Introduction HBV infection
More than 2 billion people have been infected with the hepatitis B virus, and this
includes 350-400 million chronic carriers of the virus. Of the 400million
chronically infected 15% to 40% get complication or sequel
Transmission of hepatitis B virus results from exposure to infectious blood or body
fluids such as semen and vaginal fluids, while viral DNA has been detected in
the saliva, tears, and urine of chronic carriers with high titer DNA in serum.
Vertical or Perinatal infection is a major route of infection in endemic (mainly
developing) countries.
Other risk factors for developing HBV infection include working in a health care
setting, transfusions, and dialysis, acupuncture, tattooing. Capping .
However, Hepatitis B viruses cannot be spread by holding hands, sharing eating
utensils or drinking glasses, kissing, hugging, coughing, sneezing, or
breastfeeding.
HEPATITIS B
DNA Virus
Consists of surface and core
Core consists of Core antigen and e-antigen
Most infections are subclinical, but can present with arthralgias, glomerulonephritis, urticaria
Parenteral or sexual transmission.
Hepatitis B continued
Hepatocellular necrosis occurs due to the body’s reaction to the virus rather than due to the virus itself . Therefore patients who have a severe illness from hep B are more likely to clear the virus.
SEROLOGY: Remember Acute infection has IgM , chronic has IgG
Anti Core IgM is present during acute phase( Window period ) , Anti Core IgG indicates chronic infection.
Patients with Hep B e Ag have continued active replication
Immunized or previously exposed people have Negative HBsAg and HBeAg, they have IgG Anti HB Core, and Positive anti Hep Bs and e.
HBV Serology
Genotypes : A – J
( Genotype A North Europe & US , Genotypes B and C are confined to populations in eastern Asia and the Far East, but changes in immigration patterns have resulted in an influx of Asian HBV carriers with these genotypes into the United States,Genotype D is found worldwide but is especially prevalent in the Mediterranean area, Middle East, and south Asia.Genotype E is indigenous to western sub-Saharan areas, and Genotype F prevails in Central America. Cases of genotype G have been reported in the United States and France. Genotype H has been described in Mexico. Genotypes I and J are the most recently discovered and have been observed in Vietnam and the Ryukyu Islands in Japan, respectively
Serological Patterns of Acute & Chronic Hepatitis B
Question
A 48 yo woman plans to travel to Abroad ( South America ) with her husband and 11 year old child. The family have no known history of liver disease or hepatitis and no members of the family have had immunizations for hepatitis. What immunizations would you recommend:
A . Hepatitis A vaccination for both parents and child
B . Hepatitis A Vaccination for parents and child and Hepatitis B vaccination for the child
C . Hepatitis A and Hepatitis B vaccination for both parents and the child
D . Screen parents for previous Hep A infection, and recommend Hep A vaccination for the child
E . Screen all members of the family for Hep A and B exposure.
ANSWER B
All children should now get Hep B. vaccination as babies, if they miss this they should have catch up vaccination as 11-12 year olds
Previous Hep A infection is unlikely in children and adults not in high risk populations therefore it is safe to vaccinate without antibody testing.
QUESTION
A 40 yo married man with two children was recently evaluated for fatigue and elevations of liver function tests and was found to have chronic Hep B. Physical examination reveals a few spider angiomata on his chest and upper extremities.
Labs:
HBsAg Pos
HBeAg Pos
HBV DNA90 (low)
ALT156 U/L
Albumin3.8
INR 1.5
A liver biopsy is performed and shows cirrhosis with moderate inflammatory activity
The most appropriate recommendation for this patient isA . He should receive the Hepatitis A Vaccine
B . His Wife and Childern should receive the Hepatitis B Vaccine
C . He should be treated with Interferon Alpha
D . All of the above
ANSWER: D
All patients with Liver disease should have the Hepatitis A vaccine as they have decreased hepatic reserve and the mortality of Hepatitis A in a patient with Hepatitis B is considerably increased
Household contacts of patients with Hepatitis B should be vaccinated
Patients with HBeAg are candidates for Interferon therapy, this is most likely to benefit patients with HBV DNA <200 and evidence of ongoing immune mediated liver cell damage on biopsy.
Hepatitis C
Structure of hepatitis c
Dr.T.V.Rao MD20
Hepatitis C- global infection
More than 200 million infected worldwide(the (WHO)
estimates about 3% of the world’s population has been
infected with HCV)
In 2000 that Egypt had the highest number of reported
infections22%, largely attributed to the use of
contaminated parenteral antischistosomal therapy.
Many do not experience symptoms
Chronic HCV is the only Chronic Viral infection that can be
cured by Antivirus
21
Genotypes
The sequences cluster into 6 major genotypes (designated by numbers), with sequence similarities of 60% to 70%, and more than 70 subtypes (designated by a lower-case letter) within these major genotypes,with sequence similarities of 77% to 80%.
In a study in Iraq on 230 HCV patients , Genotype 1b 44.6 % , genotype 4 36.9% ( Akram etal )
Global geographic differences exist in the distribution
ofHCV genotypes, as well as in the mode of acquisition
United States, genotype 1a is the most prevalent, accounting for approximately 57% of HCV infections, followed by genotype 1b in 17%, genotype 2 in 14%, genotype 3 in 7%, and genotype 4, 5, or 6 in less than 5% .
Genotype 1 also may be associated with more severe liver disease and a higher risk of HCC
In Europe, the most prevalent genotype is 1b (47%), followed by 1a (17%), 3 (16%), and 2 (13%)
HCV genotypes
Genotype 4 is found mainly in Egypt, the Middle East, and Central Africa. In Egypt,approximately 15% of the population is infected with HCV, and more than 90% have HCV genotype 4.
Genotype 5, although originally isolated in South Africa, is also seen in specific regions of France, Belgium, and Spain
Genotype 6 is found predominantly in Asia.
Hepatitis C
Flaviviridae family; the prototype Hepacivirus
Rapid replication rate
High mutation rate that allows him to escape the immune recognition.
Hep C infection can present as acute hepatitis, chronic hepatitis, cirrhosis, HCC or extrahepatic
Hepatitis C
Incubation period : 6-7 weeks and seroconversion time 8-9 weeks.
Acute symptomatic cases occur in 10-30% while fulminant hepatitis occurs almost exclusively in patients with HBV.
Most cases progress slowly to chronic infection. Mechanism is unknown. Viral, host and other factors play role.
Hepatitis C
Host factors:
HLA-DRB1, DQB1
Low peak levels of HCV during acute infection
Age
Ethnicity
Coinfections (HIV, Hep B)
High BMI
Hepatitis C
Viral factors:
Genotype 1B
Coinfection with >1 HCV genotype
Other Factors:
Marijuana
Alcohol
Amount of inflammation and fibrosis on liver biopsy
Corticosteroids
Hepatitis C
RNA virus
Blood Bourne i.e. Transmission from IV drug use and transfusion of blood products prior to 1990.
Can also be transmitted by snorting cocaine.
Vertical transmission and Sexual transmission is low.
Testing involves Anti HCV Antibody, and then viral load if positive.
85% of patients develop chronic infection.
Extrahepatic manifestations
Hematologic (mixed cryoglobulenimia, lymphoma)
Renal (membranoproliferative GN)
Autoimmune (thyroiditis)
Dermatologic ( porphyria cutanea tarda, Lichen palnus)
Diabetes mellitus.
Hepatitis C Diagnosis
Who should be tested? AASLD recommendations
Abnormal ALT
IVDU hx
Blood transfusion < 1992
Clotting factors <1987
Kids to HCV infected mothers
Current sexual partners to HCV infected subjects
Needle stick
Hepatitis C Diagnosis
Elisa
RIBA
PCR-RNA
Genotype
Liver biopsy
Management of Hep C
Interferon alpha with ribavirin for 6 to 12 months clears virus in approx 40% of patients.
There is an algorithm which is used to decide who is treated, but basically anyone with Hep C, high ALT and less than 40 yo. If older than 40 should have biopsy first which should at least show periportal inflammation or fibrosis.
Treatment
Counseling
Diet: NO alcohol . Smoking: controversial
Zofran( Ondansetron ) for fatigue 4 mg bid
The mainstay of treatment is Interferon and ribavirin, DAAD
Goals of treatment: eradicate HCV infection, slow disease progression, improve hepatic histology (function) and prevent hepatocellullar carcinoma
Interferon
Glycoproteins produced by cells in response to infection
Biological properties of interferons:
anti-viral , immunostimulatory , anti-proliferative anti-angiogenic
Pegylated Interferon
covalent attachment of variably configured polyethylene glycol (PEG) chains to sites on the interferon molecule delays absorption , decreases clearance rate , allows once per week dosing ,alters properties and activity of parent compound
prolongs immune activation and cytokine-derived antiviral effects
two pegylated interferons are now FDA-approved
peginterferon alfa-2a (Pegasys® - Roche)
peginterferon alfa-2b (PEG-Intron® - Schering)
Ribavirin
Guanosine analogue
active against many viruses in vitro and in vivo
mechanism of action against HCV uncleardepletion of intracellular triphosphate pools
inhibition of viral-dependent polymerase
Immunomodulatory & mutational deletion
Indications for treatment1 . stage 2-3 fibrosis and/or grade 3-4 necrosis/
inflammation on liver biopsy
2 . stage 4 fibrosis (cirrhosis) with compensated liver function
3 . genotype 2 or 3, viral load < 2 million IU/mL
4 . severe symptoms related to cirrhosis or extrahepatic symptoms (e.g., cryoglobulinemia)
5 . desire to be pregnant without risk of vertical transmission
Other issues regarding Hep C
Once pt with Hep C is cirrhotic their risk of developing hepatocellular Ca is 1-4% per year
Alcohol increases risk
Other viral hepatitis
Hep E: Acute hepatitis just like hep A unless you are PREGNANT in which case can progress to fulminant hepatitis
EBV, CMV, Herpes viruses can all cause acute hepatitis especially in immunocompromised.
QuestionA 38 yo woman was found to be Hep C positive 6 months ago after evaluation for raised AST. The infection was attributed to blood transfusions received during a car accident 15 years ago. She was pleased to learn last month that she is pregnant with her first child.
The physical examination is within normal limits . She would like further information concerning her prognosis and the risk of transmission of HCV to her husband and her child.
All of the following statements about HCV infection are true except:
A . The chance of transmission of HCV to the newborn is low in the 5% range.
B . Barrier precautions including safe sex are recommended for all couples in a monogamous relationship because of high risk of transmission to the partner
C . Low level transmission of Hep C is recognized within households (5-10%), and the risk for such transmission should be minimized by practices that avoid blood-blood exposure such as sharing dental implements and razors
D . In patients with Hep C the chance of developing cirrhosis over several decades is 20-35%
Answer B
Maternal-fetal HCV transmission is approx 5%, however if mother is co-infected with HIV then risk increases to 30%
Risk of sexual transmission between monogamous spouses is also low approx 5%
Transmission can occur between non-sexual household contacts therefore should be told to avoid sharing razors etc.
20-35% of patients with Hep C develop cirrhosis
23-year-old man was referred for abnormal LFT’s . HPI: The patient was
admitted for severe depression. His psychiatrist had obtained blood tests to
follow valproate (Depakote) therapy. Liver chemistries were abnormal (see
below). The patient was asymptomatic and denied any jaundice, fever,
abdominal pain, nausea and vomiting. He has never had blood
transfusions. He denies the use of medications other than those prescribed by
his psychiatrist. Patient admits using illicit drugs IV starting about 8 weeks
ago and has continued use to the present. PMH: Bipolar disorder
Medications: Depakote 500 mg XR qd, fluoxetine 40 mg qd, clonazepam 1 mg
prn. PH and SH: no excessive alcohol and tobacco use, no travel, recent IV
drug abuse as above
FH: father suffers from depression
Labs: Direct bili 1 mg/dL, Alk phos 188 u/L, ALT 1178 u/L, AST 746 u/L (all
significantly elevated); Anti-HCV negative on hospital day 1 and positive on
day 3, HCV-RNA PCR positive (done only on day 3); Hep A, B and D markers
are negative. Patient is diagnosed with Acute Hepatitis C
Questions:
In this case, what are the some clinical features that are typical for acute HCV?
How is the diagnosis of acute hepatitis C made?
What is the natural history for HCV infection?
What are the treatment strategies for acute HCV infection.
When is therapy initiated in chronic HCV patients and what is an example of a treatment regimen?
What are some of the limitations of available therapies?
what are the some clinical features that are typical
for acute HCV?
Most often, Hep C transmission occurs parenterally. Recent h/o of IV drug abuse suggests the possibility of hepatitis B, C, and D infection in this patient. For hepatitis C, the incubation period between the exposure and the appearance of clinical and serological evidence of acute hepatitis is between 4 and 20 weeks. The majority of patients, 40-75 %, remain asymptomatic or have mild symptoms not leading to medical attention. Our patient was asymptomatic and would not have been identified if he had not required lab follow-up for his valproatetherapy.
How is the diagnosis of acute hepatitis C made?
Clinically, acute hepatitis C is indistinguishable from other types of viral hepatitis; therefore it is important to exclude the possibility of other types of viral hepatitis by testing for HAV, HBV, and HDV markers, as was done in our patient. Laboratory diagnosis of acute HCV infection is made by documenting HCV antigen being present (going from anti-HCV negative to anti-HCV positive supports the diagnosis but can take up to 1 year to occur!).
What is the natural history of HCV infection?
An important feature of HCV is that up to 80% of patients will develop chronic hepatitis C. Chronic disease is usually diagnosed 10 or more years after the acute illness. More than 20% of those with chronic hepatitis C infection will progress to cirrhosis and eventually will develop end-stage liver disease in about 20 years. Some patients will develop hepatocellular carcinoma ~30 years after initial infection.
What are the treatment strategies for acute HCV infection?
Management of acute hepatitis is mostly supportive. Patients need to be advised to maintain healthy diet, avoid alcohol and hepatotoxic drugs. In our patient, consideration of discontinuation of valproate should be discussed with the psychiatrist. It is important to monitor patients with acute HCV for development of chronic disease (seropositive for anti-HCV> 6 months.). Interferon therapy has been tried for the treatment of acute HCV, and results have been mixed and unimpressive. Immune serum globulin does not work either.
When is therapy initiated in chronic HCV patients? and what is an example of a treatment regimen?
When the patient is seropositive for anti-HCV for greater than 6 months, patient is also seropositive for HCV RNA and patient has evidence of liver disease (LFTs are elevated).
One example: PEG INF alpha-2a or 2b + ribavirin is “standard of care” today (ribavirin dose used depends on genotype)
What are some of the limitations of available therapies?
Not all patients respond to interferon +
ribavirin therapy. Response is usually
monitored by HCV RNA testing. If patient
is not HCV RNA negative after 12 wk.of
therapy, treatment should be D/C.
Treatment must be continued for 2-4 years
to produce reasonable sustained response
rates (i.e. response after therapy has been
D/C'd).
THANK YOU