Hepatitis C

hepatitis C clinical research


WCCT Global wishes to deepen its participation in the medical and scientific initiative to more effectively treat Hepatitis C Virus

Hepatitis C (HCV) is a global disease. HCV in combination with Hepatitis B (HBV), now accounts for 75% of all cases of liver disease around the world. WCCT Global has become a leader in helping the research community better understand this disease through WCCT Global’s Hepatitis Center of Excellence.

Understanding the disease is key:

There are six basic genotypes of HCV infection in the worldwide populations, with 15 recorded subtypes, which vary in prevalence across different regions of the world. Each of these major genotypes may differ significantly in their biological effects – in terms of replication, mutation rates, type and severity of liver damage, and detection and treatment options – however, these differences are all not yet clearly understood.

Results from global epidemiological studies demonstrate wide variance in HCV prevalence patterns with the incidence of HCV being higher among less developed nations. The prevalence of hepatitis C is lowest in Northern European countries, including Great Britain, Germany and France. Higher HCV prevalence rates have been reported in Southeast Asian countries, including India (1.5%), Malaysia (2.3%), and the Philippines (2.3%). The incidence in Japan was 1.2%. Alarming rates were reported for many African nations, reaching as high as 14.5% in Egypt.

Thus, the overall data suggest that over 200 million people around the world are infected with hepatitis C – an overall incidence of around 3.3% of the world’s population. Statistically, as many people are infected with HCV as are with HIV. Many public health experts feel that unless large scale efforts to contain the spread of HCV and treat infected populations, the death rate from hepatitis C will surpass that of AIDS in coming years.

Treatment with a combination of pegylated interferon and ribavirin is the current standard of care for chronic hepatitis C. Unfortunately, nearly 50% of individuals fail to respond to this regimen (sustained virologic response [SVR] defined as undetectable HCV RNA by polymerase chain reaction (PCR)-based assay 24 weeks after the end of treatment). More specifically, up to 60% of patients with HCV genotype 1 infection, the most common genotype in the United States and 20%-30% of patients with HCV genotype 2/3 infection do not respond to initial therapy with the current standard of care. Thus, without a more effective therapy, the risk of developing liver-related complications among those who are chronically infected will increase, not peaking until after the year 2030. This has provided the impetus to develop more novel and effective therapies.

Our new and evolving understanding of the HCV lifecycle has allowed development of agents designed to interrupt viral infection and replication. It is hoped that this new knowledge will translate into effective treatment options for nearly all patients with HCV.

The HCV Lifecycle

HCV is a small, enveloped, linear, single-stranded RNA virus. The genome encodes a single polyprotein that is then processed by both host and viral proteases into smaller proteins that assist in viral replication. Research has identified several steps during this replication process that are fundamental to the HCV lifecycle and thus represent excellent Direct Anti-HCV therapeutic targets.

  • Binding, cell entry, nucleocapsid uncoating, and release
    • Viral envelope proteins (E1 and E2) bind to host CD81 allowing internalization
  • HCV translation
    • Amino acid sequencing at RER to form the HCV polyprotein
  • Polyprotein processing
    • Protease cleavage into 6 NS (nonstructural) proteins that support viral RNA replication
  • Assembly of the RNA replication complex
    • NS Proteinsare required for assembling the RNA replication complex (replicase)
  • RNA synthesis (NS5B RNA polymerase)
    • Nearly 1 trillion particles are produced each day
    • An exceptionally high mutation rate
  • Virus assembly and release
    • Phosphorylation of NS5A may trigger the virus to switch from “replication mode” to “assembly mode

World Hepatitis Day, observed on July 28 every year, aims to raise global awareness of hepatitis — a group of infectious diseases known as Hepatitis A, B, C, D, and E — and encourage prevention, diagnosis and treatment. Hepatitis affects hundreds of millions of people worldwide, causing acute and chronic disease and killing close to 1.4 million people every year.
RNA polymerase (RNAP or RNApol), also known as DNA-dependent RNA polymerase, is an enzyme that produces primary transcript RNA. In cells, RNAP is necessary for constructing RNA chains using DNA genes as templates, a process calledtranscription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses. In chemical terms, RNAP is a nucleotidyl transferase that polymerizes ribonucleotides at the 3′ end of an RNA transcript.
Hepatitis C is an infectious disease affecting primarily the liver.[1] The infection is oftenasymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure, liver cancer, or life-threatening esophageal and gastric varices.