Title: Acute Hepatitis C
1Acute Hepatitis C
By
Prof. Dr. Magdi Atta
Department of Hepatology, Gastroenterology And
Infectious Diseases Benha Faculty of Medicine
2Hepatitis C is a major health problem.
- About 175 million chronic HCV cases are found
throughout the world.
- 4 million are in the USA.
- 5 million in Western Europe.
- gt 6 million in Egypt.
- 20 of acute hepatitis cases.
- 70 of cases of chronic hepatitis.
- 40 of cases of end stage cirrhosis.
- 60 of cases of hepato-cellular carcinoma.
- 30 of liver transplants.
3- Single stranded , enveloped RNA virus which
belongs to the flaviviridae family. - Preferential replication in hepatocytes.
- Not directly cytopathic, leading to persistent
infection - High mutation rate which results in considerable
heterogeneity throughout the genome. - Classified into 6 main genotypes and more than 50
subtypes. - Classified into quasispecies.
4TRANSMISSION
- Blood transfusion and other blood products.
(Supposed to have decreased after 1990). - Needle sticks.
- Injection drug use.
- Sexual.
- Vertical.
- Tattooing or acupuncture.
- Intrafamilial.
- Organ transplants from infected donors.
- Dentists.
5Clinical Picture
- Incubation period 7-8 weeks (range 2-26 weeks).
- The disease is anicteric or subclinical in the
majority of cases (70-80). - Only 20-30 of cases show symptoms like malaise,
nausea, anorexia and upper abdominal pain
followed by dark urine and jaundice. - Acute infection can be severe but rarely is
fulminant.
6Laboratory findings
- HCV RNA (positive 1-2 weeks after infection).
- ALT (10-20 folds of the upper limit of normal at
7-8 weeks). - Antibody to HCV is usually but not always present
at the time of symptoms or elevation of ALT. - Anti HCV antibodies persist for many years.
7Criteria of Acute HCV Diagnosis
- Known or suspected exposure to HCV within the
preceding four months. - Documented seroconversion to positivity for
antibodies against HCV. - Serum alanine aminotransferase level of more than
(10-20 times the upper limit of the normal
range). - Positive test for HCV RNA.
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9Natural History of Hepatitis C Virus Infection
10- Our knowledge is limited because of relatively
recent discovery. - HCV-related liver disease is usually slowly
progressive, taking many years to produce
significant hepatic fibrosis. - The most definitive studies suggest that the
average time from infection to the development of
cirrhosis is determined by host factors.
11Factors affecting the progression of HCV
infection
(A) Host factors
- Older age (gt 40 years).
- Male gender.
- Alcohol consumption (gt 50 gm./day).
- Lower T lymphocyte response.
- Overweight, diabetes and hepatic steatosis.
12(B) Virologic Factors
- No evidence that they are directly related to
rate of disease progression
- Viral mutation and virus replication in
hepatocytes without direct cytopathic effect lead
to persistent infection. - High viral load and genotype I were proposed as
markers of more serious liver disease.
13Treatment
- Treating patients with acute disease attempting
to prevent chronicity.
14- Published studies have used standard alfa or beta
interferon monotherapy. - None have evaluated combination therapy of
interferons and ribavirin or peginterferon.
15- Small in size.
- Uncontrolled.
- Heterogeneous in
1- Patient's features. 2- Dose and duration of
treatment. 3- Follow up evaluation. 4-
Criteria used to define efficacy and safety.
16Heterogeneity of Published Studies on Interferon
Therapy of Acute Hepatitis C
Studies
Posttransfusion cases only Non-posttransfusion
cases only Mixed population of cases
7 studies 5 studies 5 studies
Patients included
Symptomatic patients only Symptomatic and
asymptomatic patients Percent of patients with
jaundice Mean pretreatment ALT levels
7 studies 10 studies 25 to 100 80 to 1.400
IU/L
Type of interferon used
Alfa interferon Beta interferon
12 studies 5 studies
17Heterogeneity of Published Studies on Interferon
Therapy of Acute Hepatitis C (cont.)
Dose and duration of therapy
Initial dose Cumulative dose Daily 3 times
weekly Daily and then 3 times weekly Duration of
therapy
0.3-10 MU 8.4-780 MU 4 studies 9 studies 4
studies 4-52 wk
Criteria for assessing response
Biochemical response only Biochemical and
virological response
5 studies 12 studies
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19Meta-Analysis Of 4 Randomized Controlled Trials
Of Interferon Alfa-2b For Acute Posttransfusion
Hepatitis C
- These 4 studies included 74 treated and 67
un-treated patients and were fairly homogeneous. - Alfa interferon therapy was given in a dose of 3
MU 3 times weekly for 12 weeks. - Interferon therapy was associated with a
statistically significant improvement in outcome,
with a 30 increase in the rate of sustained
virological response compared with no treatment.
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21- Several metaanalysis of published studies have
concluded that initiation of interferon
mono-therapy significantly reduces (by 30 to 40)
evolution to chronic hepatitis. - Tolerability of interferon has been excellent
even in symptomatic and icteric patients.
22Side Effects And Adverse Events
Similar type and frequency to those seen when
treating chronic cases.
23Alpha interferons, including alfa-2a or alfa-2b,
cause or aggravate fatal or life-threatening
neuropsychiatric, autoimmune, ischemic, and
infectious disorders. Patients should be
monitored closely with periodic clinical and
laboratory evaluations.
24Patients with persistently severe or worsening
signs or symptoms of these conditions should be
withdrawn from therapy. In many but not all cases
these disorders resolve after stopping therapy.
25Conclusion
- Available data support treatment however they are
still insufficient to get firm conclusions about
- 1- Which patients to teat?
- 2- When therapy should be started?
- 3- What regimen is optimal?
26Recommendations
- Future studies of adequate size and design should
focus on
- 1- Efficacy and tolerability of peginterferons.
- 2- Whether therapy should be started immediately
after diagnosis or delayed for 2 to 4 months to
avoid treatment of patients who spontaneously
recover. - 3- Patients with genotype 4.
27Obstacles
- Difficulties in diagnosis.
- Treatment
- Cost.
- No published studies on patients with
- Genotype 4.
- Schistosomiasis.