Advanced liver damage is common in people with undiagnosed hepatitis C in US survey

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Around one in five people with hepatitis C in the United States who do not know of their infection may already have advanced liver damage and be in urgent need of treatment, according to a cross-sectional survey of participants in the National Health and Nutritional Examination Survey (NHANES) presented by Prowpanga Udompap at the International Liver Congress in Vienna, Austria, on Saturday.

The United States Centers for Disease Control and Prevention (CDC) recommends that everyone born between 1945 and 1965 – the 'baby boom' generation – should have a test for hepatitis C virus (HCV) at least once, due to the high prevalence of hepatitis C in this age group.

However, primary care physicians have been slow to implement the guidance, and many people who might have been at risk of acquiring hepatitis C during military service, as a result of blood transfusion or through injecting drugs are unaware of the availability of hepatitis C testing and new curative treatment.



Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.


Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

alanine aminotransferase (ALT)

An enzyme found primarily in the liver. Alanine aminotransferase may be measured as part of a liver function test. Abnormally high blood levels of ALT are a sign of liver inflammation or damage from infection or drugs.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.


positive predictive value

When using a diagnostic test, the percentage of those testing positive who are correctly diagnosed. This will vary according the prevalence in the local population.

As people infected with hepatitis C age, their risk of progressive liver damage grows, but without diagnosis many people infected in the 1960s and 1970s will be unaware that they have suffered liver damage.

Without treatment, people with advanced fibrosis may progress to advanced stages of liver cirrhosis, suffer liver failure and serious extra-hepatic symptoms or develop liver cancer.

Treatment guidelines recommend that people with advanced fibrosis (stages F3 and F4) should receive immediate treatment owing to the high risk of liver disease progression.

In order to quantify the scale of advanced fibrosis in people with undiagnosed hepatitis C, Prowpanga Udompap and colleagues of Stanford University used data from the National Health and Nutrition Examination Survey (NHANES II), a cohort of 62,000 American adults. In this cohort 45,000 people have been tested for HCV antibodies, of which 591 were positive and 420 had chronic HCV infection confirmed by RNA testing. Of these, 417 had AST and ALT liver enzyme measurements and 163 of these had responded to questions about HCV awareness, and this subset was used to quantify the prevalence of cirrhosis among undiagnosed people. Forty-nine per cent were unaware of their HCV infection.

The researchers used the FIB-4 system to calculate the risk of advanced fibrosis. FIB-4 is a validated algorithm for calculating the stage of liver damage using ALT, AST, platelet levels and age. It has a high positive predictive value for diagnosing F3/F4 fibrosis.

This study used FIB-4 cut-offs of <1.45 for low probability of fibrosis, 1.45-<3.25 for intermediate fibrosis, and >3.25 for advanced fibrosis (F3 and F4).

Of the respondents with known HCV infection, the proportion with a high, intermediate and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively; in those with undiagnosed HCV the results were 19.1%, 30.9%, 50.0%, respectively.

Using the aspartate aminotransferase/platelet ratio index (APRI) produced a similar result, although the estimate of advanced fibrosis in undiagnosed people was lower (11%).

A recent study by the US CDC, which used FIB-4 to calculate liver fibrosis stage in people with a positive HCV RNA test between 2010 and 2013, found that 40% of all patients, and 46% of those in the 1945-1965 birth cohort, had advanced fibrosis (F3 or F4).


Udompap P et al. Advanced fibrosis is common in individuals whose hepatitis C has not been diagnosed: Results from the National Health and Nutrition Examination Survey 2001-2012. J Hepatology 62 (50th International Liver Congress), abstract 0120, 2015.