Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA

Abstract

Objectives: Effective oral therapies for hepatitis B and C have recently been developed, while there are no approved pharmacological therapies for alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD). We hypothesise that fewer advances in fatty liver diseases could be related to disparities in research attention.

Methods: We developed the Attention-to-Burden Index (ABI) that compares the research activities during 2010-2014, and an estimate of disease burden of these 4 major liver diseases. The resulting ratio reflects either overattention (positive value) or inadequate attention (negative value) compared with disease burden. The mean research attention and disease burden were calculated from 5 and 6 different parameters, respectively. The efficacy rate of current pharmacological therapies was assessed from published clinical trials.

Findings: The mean research attention for hepatitis B and C was 31% and 47%, respectively, while NAFLD and ALD received 17% and 5%. The overall burden was 5% and 28% for hepatitis B and C, and 17% and 50% for NAFLD and ALD. The calculated ABI for hepatitis B and C revealed a +6.7-fold and +1.7-fold overattention, respectively. NAFLD received an appropriate attention compared with its burden, while ALD received marked inadequate attention of -9.7-fold. The efficacy rate of current pharmacological agents was 72% for hepatitis B, 89% for hepatitis C, 25% for non-alcoholic steatohepatitis and 13% for alcoholic hepatitis. Importantly, we found a positive correlation between the mean attention and the efficacy rate of current therapies in these 4 major liver diseases.

Interpretation: There are important disparities between research attention and disease burden among the major liver diseases. While viral hepatitis has received considerable attention, there is a marked inadequate attention to ALD. There is a critical need to increase awareness of ALD in the liver research community.

Keywords: Hepatitis B virus; Hepatitis C virus; Non-alcoholic fatty liver disease; PUBLIC HEALTH; alcoholic liver disease.

Figure 1

Parameters of research attention to the four major liver diseases. The relative level of attention devoted to each liver disease from different parameters: (A) detailed analysis of all presentations at the two major annual scientific liver meetings (AASLD and EASL); (B) research opportunities offered by public agencies in the USA and in the EU; (C) ongoing registered clinical trials (ClinicalTrials.gov); (D) scientific publications (PubMed). AASLD, American Association Study of Liver Diseases; AH, alcoholic hepatitis; ALD, alcoholic liver disease; EASL, European Association for the Study of the Liver; EU, European Union; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NIH, National Institutes of Health.

Figure 2

Calculation of mean research attention to the four major liver diseases. The mean research attention to the four main liver diseases (HBV, HCV, NAFLD and ALD) was calculated from five parameters: scientific publications (PubMed); research opportunities offered by public agencies in the USA and the EU; ongoing registered clinical trials (ClinicalTrials.gov); detailed analysis of all presentations at the two major annual scientific liver meetings (AASLD and EASL); and number of drugs in development in the pipeline of 38 major pharmaceutical companies. AASLD, American Association Study of Liver Diseases; ALD, alcoholic liver disease; EASL, European Association for the Study of the Liver; EU, European Union; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, non-alcoholic fatty liver disease.

Figure 3

Estimation of mean disease burden to four main liver diseases. The mean disease burden to the four main liver diseases (HBV, HCV, NAFLD and ALD) was calculated from seven parameters: total number of US hospitals discharged, US hospitalisation costs, OLTY-EU, OLTY-US, cirrhosis-US, fibrosis and US mortality. ALD, alcoholic liver disease; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, non-alcoholic fatty liver disease.

Figure 4

ABI for the four major liver diseases. ABI was calculated using the ratio of mean research attention (comprising different parameters shown in figure 1) to mean disease burden (comprising the parameters shown in figure 2) of the four main liver diseases. A value >1 reflects overattention compared with the disease burden, while a value <1 reflects inadequate attention. ABI, Attention-to-Burden Index ALD, alcoholic liver disease; HBV, hepatitis B virus; HCV, hepatitis C virus; NAFLD, non-alcoholic fatty liver disease.

Figure 5

Correlation between the efficacy of current drug therapies for hepatitis and the mean research attention. (A) Current mean rate of efficacy for therapeutic drugs; (B) correlation between the efficacy of current drug therapies for hepatitis and the mean research attention. The efficacy of current drug therapies to treat chronic hepatitis (HCV), chronic hepatitis B (HBV), NASH and AH was calculated based on large published clinical trials (see Methods section). Definition criteria of drug efficacy for each of the four type of hepatitis were: HCV: sustained viral response at 12 weeks; HBV: achievement of end points suppressing viral replication; NASH: reduction in NAS or fibrosis score; AH: effect on short-term mortality rate. AH, alcoholic hepatitis; HBV, hepatitis B virus; HCV, hepatitis C virus; NAS, NAFLD Activity Score; NASH, non-alcoholic steatohepatitis.