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Hepatocellular carcinoma risk, cirrhosis and hepatitis C

Evidence-based medicine

Gerry Morrow

Monday, 03 December 2018

AdobeStock_176969783_cirrhosis.jpgCirrhosis is a process where normal, smooth liver structure becomes distorted by nodules surrounded by fibrosis. Over several years this affects the liver's synthetic, metabolic and excretory actions.

Over 60,000 people in England and Wales have cirrhosis.1 Liver disease is the only major cause of mortality and morbidity which has been increasing for chronic, non-communicable diseases.  Between 2005–2015, there was an almost 50% increase in the number of admissions with a primary diagnosis of cirrhosis in England.

The most common risk factors for cirrhosis in the UK and Europe include alcohol misuse, hepatitis B and C infection, obesity and type 2 diabetes.

For most patients once cirrhosis has occurred, it is usually irreversible. People with cirrhosis are generally well and have no clinical symptoms or signs. Eventually, complications ensue including jaundice, ascites, variceal haemorrhage, or hepatic encephalopathy, due to portal hypertension and/or hepatocellular failure.

The prognosis of cirrhosis is influenced by several factors, including the underlying cause of the disease and persistence or changes to a harmful lifestyle, including alcohol consumption and/or injecting drugs.

There is one category of patient who has a greater chance of cure but also ominously have an increased risk of cirrhosis developing into hepatocellular carcinoma. 

Hepatitis C infection was previously considered a ‘silent’ disease until it manifested as decompensated liver failure with no prospect of cure. It is still largely hidden as of the 160,000 people with hepatitis C in England, over 50% are undiagnosed.

From recent prevalence studies2 it has been reported that 30% of people with hepatitis C have cirrhosis and worryingly further recent research3 has found a three times greater risk of developing hepatocellular carcinoma in these people than with other causes of cirrhosis.

It is postulated that hepatitis C RNA is carcinogenic4 and is particularly associated with the genotype 3 variant. The reason for this is that the HCV core RNA protein has been shown to play a key role in various oncogenic processes5 including downregulation of tumour suppressor genes, activation of oncogenes, dysregulation of apoptosis, immune modulation, increased inflammation and increased cell turnover.  

However, we now have oral treatment regimen for 8-12 weeks of ribavirin and pegylated interferon alpha which has been found to be effective in over 95% of individuals with hepatitis C infection.6 It is important therefore to raise awareness of the success of treatment and the risks of delays in therapy.

Since the at-risk groups for this infection include people who inject drugs (PWID) and men who have sex with men (MSM), particularly in lower socioeconomic groups, diagnosis and successful therapeutic interventions have proved challenging. Despite this challenge testing rates for hepatitis C virus infection have increased partly because of increasing awareness and focused campaigns on these PWID, MSM groups and the prison population.

The overall aim is to over the next 10 years dramatically reduce complications from cirrhosis and rates of entirely preventable hepatocellular carcinoma in this group of individuals.

Ultimately, it seems essential and appropriate to deploy a high profile public health strategy7 to utilise resources maximally to provide cost-effective and curative drug treatments for these high-risk groups to save lives. 

Related OnMedica content:

Chronic hepatitis C infection: a case history on the differential diagnosis and management of this liver condition.


  1. Cirrhosis. Clinical Knowledge Summaries, 2018
  2. The Uncomfortable Truth. Hepatitis C in England: The State of the Nation. The Hepatitis C Trust, 2013
  3. Ioannou GN. Differences in hepatocellular carcinoma risk, predictors and trends over time according to etiology of cirrhosis. PLOS One, 2018.
  4. Lemon SM, McGivern DR. Is Hepatitis C Virus Carcinogenic? Gastroenterology 2012;142:1274–1278
  5. Won Jeong S, et al. Hepatitis C virus and hepatocarcinogenesis. Clinical and molecular hepatology 2012; 18(4): 347-356
  6. Hepatitis C in England - 2018 report. Working to eliminate hepatitis C as a major public health threat. Public Health England, 2018.
  7. Eliminating Hepatitis C in England. All-Party Parliamentary Group on Liver Health Inquiry Report, March 2018.


Author's Image

Gerry Morrow

With a keen interest in evidence-based medicine and patient involvement, Gerry has over twenty years’ experience working as a GP, based initially in Worcester and then in the rural practice of Allendale. Now Medical Director of Clarity Informatics, a leading IT healthcare solutions provider, Gerry is leading a globally recognised team of clinicians and researchers, and is also directly responsible for the production and delivering of Clarity’s clinical guidance which forms the clinical content of NICE’s Clinical Knowledge Summaries (CKS) service. Gerry is also a clinical non-executive director of the North East Ambulance Service, responsible for operating patient transport and ambulance response services across a region covering 3,200 square miles and a population of 2.7 million people.
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