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Past, Present, and Future of Hepatitis C Treatments

Discovered in 1989, hepatitis C is a severe disease for which there is still no vaccine today. It is widespread, affecting more than 143 million people worldwide andcausing the death of 399,000 people every year(1). Due to its high death rate, hepatitis C is the topic of much research as scientists strive for a definitive cure.

The Hepatitis C Virus

The hepatitis C virus (HCV) is a member of the Flaviviridaefamily and is responsible for the transmission of the hepatitis C disease. This enveloped, single-stranded RNA virus can be spread by blood-to-blood contact or vertically transmitted from an infected pregnant woman to the baby during the gestation (1,2).

There are seven genotypes of HCV that are divided into many subtypes, of which genotypes 1 and 2 are principally involved in almost all cases of Hepatitis in the United States and Europe. Early determination of the genotype is crucial for defining treatment and understanding disease symptoms (2,3).

In almost all cases, the hepatitis C virus persists in the liver after infection. Despite the fact that patients do not initially show clear symptoms, over the course of years, they can develop liver disease or cirrhosis (3). This is designated as chronic hepatitis C. On the other hand, there are cases of hepatitis C that involve acute infection, which rarely manifests in clear symptoms and resolves spontaneously.

Individuals with chronic hepatitis C may show a vast number of signs and symptoms after just a few years (3). The most common symptoms include fatigue, cognitive issues, fever, abdominal pain, and the skin turning yellow. This is due to structural changes in the liver that can cause jaundice (4). Some individuals may develop cirrhosis and in many cases, subsequently, liver cancer. In most of these cases, liver transplantation is the only possible treatment. These patients often experience the typical symptoms of cirrhosis such as easy bruising, hepatic encephalopathy, fever, and ascites, among others (1,4).

Treatments

Due to the absence of an effective vaccine, prevention is still the main tool for combating hepatitis C today. Patients diagnosed with advanced chronic hepatitis C are advised to follow a strict diet and suppress alcohol consumption (4).

Modern protein characterization methods and purification techniques have also allowed laboratories to develop potent antivirals that have improved the treatment of chronic hepatitis C. The direct administration of the suitable antiviral is related to the the stage of the disease and in a vast number of cases, infected individuals are cured with treatment (5).

New antivirals, like the two commonly combined hepatitis C treatment drugs pegylated interferon-α and ribavirin, also show fewer secondary effects compared to previously employed treatments (5).

One of the most popular direct-acting antiviral (DAA) therapies that has been developed is Sofosbuvir, a uridine nucleotide analog, which inhibits the hepatitis C RNA-dependant RNA polymerase and consequently suppresses viral replication (6). Simeprevir, also known as TMC435 is another antiviral that acts as a hepatitis C virus NS3 protease inhibitor (7). Both drugs have revolutionized the treatment of hepatitis C in the past few years. This is a significant discovery, considering that until recently, this disease was taking the lives of thousands of individuals as there was no efficacious treatment.

The challenge that medicine faces today is the reduction of the costs required to synthesize these and more antivirals in order to make them increasingly accessible to people infected with hepatitis C.

SOURCES:

  1. http://www.who.int/news-room/fact-sheets/detail/hepatitis-c
  2. Gesell J, et al. Design, high-level expression, purification and characterization of soluble fragments of the hepatitis C virus NS3 RNA helicase suitable for NMR-based drug discovery methods and mechanistic studies. Protein Engineering, Design and Selection, Volume 14, Issue 8, 1 August 2001, Pages 573–582, https://doi.org/10.1093/protein/14.8.573
  3. Chan Shiu-Wan. Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence. World J Gastroenterol. 2014 Mar 21; 20(11): 2785–2800. Published online 2014 Mar 21. doi:  10.3748/wjg.v20.i11.2785
  4. Cilio U, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016 Jan 7; 22(1): 232–252.

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