Acute Hepatitis C

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Acute Hepatitis C
By
Prof. Dr. Magdi Atta
Department of Hepatology, Gastroenterology And
Infectious Diseases Benha Faculty of Medicine
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Hepatitis 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.

• HCV accounts for

• 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.

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• HCV virus

• 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.

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TRANSMISSION

• 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.

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Clinical 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.

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Laboratory 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.

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Criteria 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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Natural History of Hepatitis C Virus Infection
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• 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.

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Factors 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.

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(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.

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Treatment

• Rationale

• Treating patients with acute disease attempting
  to prevent chronicity.

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• Types

• Published studies have used standard alfa or beta
  interferon monotherapy.
• None have evaluated combination therapy of
  interferons and ribavirin or peginterferon.

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• Published Studies

• 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.
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Heterogeneity 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
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Heterogeneity 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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Meta-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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• 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.

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Side Effects And Adverse Events
Similar type and frequency to those seen when
treating chronic cases.
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Alpha 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.
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Patients 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.
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Conclusion

• 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?

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Recommendations

• 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.

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Obstacles

• Difficulties in diagnosis.
• Treatment

• Cost.
• No published studies on patients with

• Genotype 4.
• Schistosomiasis.

• No available vaccine.