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Hepatitis C Virus Complications and Treatments

Amylee Martin
University of California Riverside
School of Medicine - Class of 2021

Hepatitis C (HCV), along with Hepatitis A and B, are the most common of the hepatitis viruses.6 Hepatitis C differs from Hepatitis A and B in that it often results in a chronic infection. This chronic infection from HCV is the most frequent reason a person would need a liver transplant.4 Although a large percentage of the cases of Hepatitis C are asymptomatic, 50% to 80% of HCV infections will result in chronic hepatitis.1 Since the virus is often subclinical or presents with mild generalized prodromal symptoms, 50% of individuals with the disease are unaware they are infected.6 Moreover, a chronic HCV infection progresses very slowly; therefore, not all cases will result in symptomatic liver disease.1

Hepatitis C belongs to the Flaviviridae family of viruses.4 All Flaviviridae viruses are enveloped positive sense single stranded RNA viruses with an icosahedral capsid.4 The virally encoded RNA polymerase lacks 3’ to 5’ exonuclease proofreading activity, which results in high antigenic variability for the virus, which creates a challenge for engineering a vaccine.5 Another notable feature of HCV is the presence of cryoglobulins in the blood.5 Presence of HSV is first detected with anti-HSV ELISA. However, in order to confirm an active infection, HCV RNA must be detected via RT-PCR for HCV RNA.4

Hepatitis C is often referred to as non-A, non-B post-transfusion hepatitis.4 The reason for this is that HCV is transmitted in the blood and was often transmitted through blood transfusions prior to 1992.6 Besides blood transfusions, common routes of infection include IV drug use, accidental needle sticks, and hemodialysis.4 Although less likely, HCV can also be transmitted via sexual intercourse.4

Due to chronic inflammation and infection of the liver, cell death and fibrosis often leads to cirrhosis. Of those with chronic infections, 5 – 30% will develop cirrhosis over a 20-30 year period.1 Development of cirrhosis is often silent.1 Laboratory findings of cirrhosis include: increased serum bilirubin, hypoalbumenia, decreased platelet count, elevated ALT/AST.1 Elevated AFP is often associated with cirrhosis and HCC and is an indication for imaging the liver.1 Cirrhosis often leads to variceal hemorrhage, ascites, and/or encephalopathy.1 The best clinical predictor for development of cirrhosis is the amount of inflammation and fibrosis present in the liver, when first diagnosed with HCV. This can be done through a liver biopsy. According to UpToDate: “Patients with mild inflammation (portal inflammation alone or with only focal periportal extension) and no fibrosis had only a 1.2 percent annual risk of progressing to cirrhosis. Patients with moderate chronic hepatitis (periportal inflammation usually involving more than 30 percent of the limiting plate) had a 4.6 percent annual risk of developing cirrhosis; more than 90 percent developed cirrhosis within 20 years of the time of the biopsy (which was not the onset of infection). Nearly all patients with severe inflammation or bridging fibrosis developed cirrhosis within 10 years.”1 Excessive alcohol intake can accelerate the cirrhotic process.1 Due to the ability of the liver to regenerate itself, hepatic cirrhosis can often lead to cancer due to constant attempts to replace dying cells.5 In the USA, HCV accounts for 33% of HCC cases.1

Several studies have found that between 40 to 70 percent of HCV patients will develop one or more extrahepatic manifestations, which affect body systems outside the liver.7 Therefore, clinicians must consider this risk factor for HCV patients. The cause of these extrahepatic manifestations is unknown, despite being very common.1Symptoms to be alert for include fatigue, joint pain, numbness and tingling in limbs, muscle pain, severe itching, dry mouth and eyes, insulin resistance, kidney disease, thyroid disease, and other conditions. These symptoms lead to clinical complications including cyroglobulinemia, renal disease, dermatologic disorders, diabetes, and lymphomas. Some experts feel that cryoglobulin, an abnormal blood protein, is the key area to research in regards to improving the treatment for patients with extrahepatic manifestations.7 Extrahepatic manifestations have a major impact on patient morbidity, mortality, and medical costs.7 However, curing the Hepatitis C infection appears to lower the patient’s risk for developing extrahepatic manifestations.

Modern day antivirals can be used to effectively treat HCV.2 However, oral anti-viral vaccines are expensive.2 Tailored anti-viral treatments are used depending on HCV genotype.4 Most of these antiviral drugs inhibit viral proteases and polymerases.4 Interferon should be avoided due to side effects (flu­like symptoms, fatigue, neuropsychiatric symptoms, and hematologic effects).2 Ribavirin is a common antiviral used.4 If prescribed, however, development of anemia must be monitored, and while being treated, reproduction should be avoided by both males and females.2 Patients who are not immune to HAV and BAV should be vaccinated against these viruses.2

Funding: None.
Conflict of Interest: None.
Authorship: Author is entirely responsible for the content of this manuscript.
Requests for reprint should be addressed to Amylee Martin, University of California School of Medicine, 900 University Ave., Riverside, CA 92507

1. Bloom, Allison. Clinical Manifestations and Natural History of Chronic Hepatitis C Virus Infection. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed August 13th, 2018.

2. Bloom, Allison. Overview of Management of Chronic Hepatitis C Virus Infection. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed August 13th, 2018.

3. Kanda T, Nakamoto S, Nakamura M, et al. Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection. Journal of Clinical and Translational Hepatology. 2014;2(1). doi:10.14218/jcth.2013.00025. (figure)