The Power of 'Big Data' and the Impact of Screening on Hepatitis C Survival Rates

April 15, 2014
Desiree Cox, MBBS, PhD

A large multinational observational study of patients with hepatitis C reveals etiology does not play a major role in HCV survival rates and that early detection and access to treatment have a greater impact.

There is wide regional variation in hepatitis C virus (HCV) survival around the world, ranging from less than 3 months in some parts of Africa to more than 5 years in parts of Asia such as Japan and Taiwan.

Addressing the audience during a general session at the 2014 EASL International Liver Conference in London, Phillip Johnson, MD, FRCP, Clinical Academic Programme lead (Cancer) at the University of Liverpool, UK, reported results of the analysis of a large database of recorded data from 5,890 patients from 4 major HCV centers from around the world. The study is the result of an international collaboration aimed at examining the influence of various factors on regional HCV survival.

According to Johnson, “Several suggestions have been made to explain these differences, including etiology, stage of the disease at presentation, stage of the underlying liver disease, and differences in access to treatment opportunities.”

He said that previous attempts to examine this issue “have been limited by the absence of closely aligned data sets across the various countries.” The following table lists the 4 centers involved in the study and indicates the incidence and number of patients from which data was taken.

Center/Country

Incidence

Number of patients used in the analysis

UK

(Birmingham and Newcastle)

Low incidence area

(a variety of etiologies)

1,356 patients

Japan

(Ogake Prefecture)

High incidence area

(predominantly HCV, more then 2/3 patients)

2,600 patients

Hong Kong,

(Northeast Region

High incidence area

(predominantly HBV (80% of patients in the data)

1,100 patients

Spain

(Pamplona)

Medium incidence area

(HVC(36%),HBV(9%)

834 patients

The data was analysed in terms of patients’ age, gender, ethnicity, etiology, biomarkers, tumors (including tumor site and stage as explained by TNM), Charles-Pugh (C-P) score for liver function, whether or not the patient had been screened, treatment, and survival.

“The differences in survival from hepatitis in each region were dramatic,” said Johnson. “The survival rate in Japan was nearly 48 months, contrasting starkly with Hong Kong China, which had a survival rate of 7.2 months. The UK and Spain were somewhere in between. Age, and gender did not appear to be significant explicators of this difference in survival rate. C-P scores were similar for each group (the majority of patients were C-PA).”

A univariant analysis of the data showed that following factors influenced survival: bilirubin, albumin, AFP, tumor size, multifocality, whether or not there is vascular invasion, and etiology. However a multivariable analysis showed that etiology did not significantly influence survival; in short, etiology dropped out of the model completely.

“The factors that had the biggest impact on survival were vascular invasion, tumor type, whether or not the disease was multifocal, AFP, and bilirubin,” said Johnson. Access to curative treatment was also a major factor in improving survival, with over 70% of patients in Japan having access to curative or potentially curative treatment.

“The results of the impact of screening on survival were particularly striking when you compare Europe (where we have ad hoc screening), Japan (where you have intensive screening with ultrasound, CT scanning, and serological biomarkers), and Honk Kong (where there is no screening). It suggests that in countries where you have intensive screening survival tends to be long (nearly 4 years in Japan), and in places where there is no screening survival tend to be short.”

Could this simply be that Japanese patients are somehow different? Or could these results be due to lead-time bias? Analysis of the survival rates from 1968 (before any formal screening when the overall survival was 2.6 months and less than 2.5% of patients received curative treatment) to present suggest that ethnic difference was not a factor.

Johnson cautioned that “a study such as this has major limitations” due to the range and differences in the quality of data, treatment patterns, impact of lead-time bias, and differences in the quality, nature, and thoroughness of screening procedures. “It also seems to be the case that patients who have ready access to health care and those undergoing regular follow up are likely to be diagnosed earlier even in the absence of a full HCV screening program, and this will influence the time of diagnosis and the apparent survival rate.”

The most significant finding of this surveillance “big data” study is that etiology does not appear to have a significant influence on survival. Johnson stressed that further collaboration and research is needed in this area of HCV research.