Acute Hepatitis C: Timely and Effective Treatment
Identifying the nature of the disease and educating patients on the warning signs of an acute bout of hepatitis C
By Kelly V. Fitzpatrick, OMS IV
ABSTRACT: Hepatitis C affects an estimated 4.1 million Americans according to the Centers for Disease Control. It is the number one cause of liver transplants and liver related deaths in the United States. The diagnosis of this disease is not one of easy acquisition due to the common benign nature of the asymptomatic prodromal phase. However, once the diagnosis has been made, there is promising data that demonstrates effective treatment for acute hepatitis C. Treatment with interferon alfa-2b has revealed a 98 percent success rate in one particular study. Clinicians should be aware of the nature of this disease and effectively educate their patients on the warning signs of an acute bout of hepatitis C. During this review of literature, it becomes apparent that additional research is needed to provide more accurate diagnostic tools to quickly identify this potentially debilitating disease.
Hepatitis C was formerly known as “non-A, non-B” hepatitis. In 1988, one of the first molecular diagnostic tools was developed to identify the hepatitis C virus (HCV), creating a lab test that provided an accurate and precise diagnosis of the disease.1 The investigators utilized polymerase chain reaction (PCR) to isolate the HCV RNA, which lead to the advent of a useful diagnostic laboratory tool via a patient’s blood serum. This immense finding has saved many lives by allowing researchers to develop more specific treatment and screening tools for this disease.
Initially identified as a significant health problem among post-transfusion patients prior to 1992, currently a large portion of the hepatitis C community is comprised of intravenous drug abusers. Once the screening test became available, the acquisition of HCV from blood products began to dwindle. The current American Association for the Study of Liver Diseases (AASLD) recommendation for screening for hepatitis C are limited to intravenous drug abusers, individuals ever receiving clotting factors prior to 1987 or receiving blood/organ products before 1992, chronic dialysis patients and patients with any evidence of hepatic disease. It is also recommended that health care workers with a possible needle stick or mucosal exposure to hepatitis undergo screening. The same is true for children born to HCV-positive women. Sexual transmission is also a possibility and should be considered in those with HCV-infected partners2. The previous population groups mentioned are those at risk for transmission of this disease and careful observation and screening should be administered by the individual’s physician.
Acute Symptoms
The predominant cases of acute diagnosis are from patients that have a high suspicion of their exposure to hepatitis C due to their professional or recreational lifestyle. There are a few molecular diagnostic tools on the forefront for making the acute diagnosis.
Unfortunately, these tests are imperfect at this point. In addition there are few warning signs in the acute phase of the disease. Although, there are a few symptoms that the patient and clinician can look for during a hepatitis infection. Jaundice, fatigue, dark urine, pruritus, abdominal pain, nausea and loss of appetite are among the more common symptoms of HCV infections. These non-specific findings make the diagnosis difficult. A clinician should be aware of these symptoms, especially in a high risk patient.
Eighty percent of Hepatitis C patients are commonly asymptomatic until the disease has taken on a severe and chronic manifestation of the liver. Much like Human Immunodeficiency Virus (HIV), once the disease has progressed to a symptomatic state, the prognosis becomes drastically worse than that of an early diagnosis.
Diagnostic Confirmation
The current mode of initial diagnosis is by Anti-HCV antibodies, which is then followed by a HCV RNA quantitative level using polymerase chain reaction (PCR) to assess the extent of the infection before starting treatment.2 The HCV RNA will typically be revealed in about one to three weeks. The Anti-HCV antibodies will be present approximately 50 days after infection.3 Therefore, a patient may be negative for the antibodies, but positive for the HCV RNA in an acute bout of hepatitis C. From a clinical perspective, if a clinician suspects an infection and there is a negative antibody test, a qualitative HCV RNA should be ordered to rule out the disease.
Diagnosis of hepatitis C should also be followed with genotyping. There are six different genotypes, all of which have their own geographical distinction. The genotype is a good prognostic tool to assess the response to treatment. Genotypes 2 and 3 have been shown to achieve a sustained response to treatment of chronic hepatitis C. Genotype 1 accounts for the majority (71.5 percent) of hepatitis C cases in the United States.4 It has demonstrated a 55 percent sustained virologic response (SVR) and Genotypes 2 and 3 have shown greater than 80 percent SVR.5
According to the Jaeckel et al. study, the diagnostic inclusion criteria for acute hepatitis C are determined by a few biological markers. The patient must be positive for HCV RNA and elevated alanine aminotransferase (ALT). There must also be at least one of the following present in the infected individual to be considered in the acute phase: an elevated ALT above 350 U/L with a documented negative test the year earlier, a known or suspected HCV exposure in the previous four months, or seroconversion of anti-HCV antibodies.6 These tests are sensitive during the acute phase of the disease, but non-specific. The same markers are present in the chronic phase of the disease as well, which makes the determination of treatment a little more difficult. If lab data is unavailable on a patient, the only information that can be provided to the clinician is from the patient themselves. Due to the nature of transmission, patients may feel uncomfortable discussing high risk behavior with their physician. This compromises the reliability of subjective evaluation, which is a very important tool in early recognition.
Immunity
Approximately 15 percent of patients will spontaneously shed the virus and become free of HCV RNA and Anti-HCV antibodies. It has also been shown that the acute icteric state of this disease has a higher incidence of resolution than the asymptomatic acute hepatitis state.3
The degree of effective CD4+ helper T cell response has been shown to directly correlate with the likelihood of spontaneous disease resolution. An effective T cell response to the HCV surface antigens, nonstructural proteins (NS3, NS4, and NS5), has shown a significant association to the probability of a spontaneous resolution of acute hepatitis C.7 This significant finding may lead researchers in the right direction to establish a vaccine or an effective prophylactic regimen.
Treatment
Many studies have demonstrated effectiveness in acute hepatitis C using interferon alpha-2b (INF a-2b).6, 8, 9, 10 Success with this product have ranged anywhere from 75 to 98 percent sustained virologic response. The study that demonstrated the most effective virologic response in patients treated the acute hepatitis C group for a total of 24 weeks. They began treatment with 5 million U of INF a-2b subcutanously every day for four weeks. The therapy then progressed to administration three times per week for 20 weeks. Forty-two out of 43 (98 percent) patients who completed the study revealed undetectable levels of HCV RNA in their serum. The average time of infection from the start of therapy was 89 days. This study was not biased to genotype, sex, icteric state or mode of transmission.6 This demonstration for effective treatment of acute hepatitis C is very encouraging to the medical community. The only major concern for clinicians is the ability to recognize the acute phase of the disease, especially in the asymptomatic patient. Patients may be unaware of possible symptoms or may be frightened to seek medical attention due to the nature of their attainment of the disease.
At this point, there are no large scale studies observing the effect of ribavirin in addition to interferon. In 2005, a case study was reported that revealed successful treatment with this combination.11 Perhaps this combination therapy will be considered for analysis in the near future.
Current clinical trials are being conducted in an effort to find a superior treatment to the present standard. One hopeful combination is therapy with thymosin and interferon.12 Thymosin is a product of the thymus gland that promotes the production of T cells. This increase in T cell activity may amplify an individual’s immunity to the virus presumably leading to a decreased manifestation of the disease.
Prevention
Patient and blood product screening are important preventative tools in order to avoid future infections. This has been done on a regular basis since the arrival of the molecular diagnostic tools. This screening process has eliminated a number of cases of hepatitis C. Blood product distribution does not appear to contribute significantly to the etiology of this disease.
The source of true prevention becomes apparent. The clinician can play a crucial role in averting the incidence of hepatitis C. When trying to prevent this disease, patient education is very critical. Many patients who participate in the high risk activity that is associated with this infectious process are either unaware or unconcerned with the potential outcome. The physician should be able to identify these risk factors and encourage the patient to participate in counseling. Community education is also a key aspect in prevention. The solution might include classes given to high school students in order to educate them on the potential outcomes of risky behavior and what to look for if they do choose to engage in high risk behaviors.
Promising Research for the Future
In 2000, Shioda A et al. found a correlation between IgM hepatitis C core antibody and ALT elevation in chimpanzees.13 Even though this study is not a human model, it does provide some promising results. Hopefully in the near future we may be able to utilize a molecular marker, such as IgM, to provide clinicians a definitive diagnosis of hepatitis C in its acute phase. An early diagnosis would possibly lead to a more effective treatment and turn this pandemic disease into a trend of decreasing prevalence.
Summary
Early recognition of hepatitis C, within four months of exposure, appears to allocate effective treatment with interferon a-2b. It has been demonstrated that treatment can be up to ninety-eight percent effective, thereby preventing progression to chronic disease6. It does, however, become difficult when the patient is asymptomatic and does not seek medical attention. Clinicians should be aware of the potential risk factors of this disease. They should actively participate in patient and community education in order to decrease the incidence of the potentially debilitating sequelae, chronic hepatitis C.
Kelly Fitzpatrick is a fourth year medical student at the Edward Via Virginia College of Osteopathic Medicine, Blacksburg, Virginia. He will be graduating this June and will pursue an Orthopeadic Surgery residency in the U.S. Army.
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