MAFLD Considerations as a Part of the Global Hepatitis C Elimination Effort

An International Perspective

Yasser Fouad; Jeffrey V. Lazarus; Francesco Negro; Markus Peck-Radosavljevic; Shiv K. Sarin; Peter Ferenci; Gamal Esmat; Hasmik Ghazinian; Atsushi Nakajima; Marcelo Silva; Samuel Lee; Massimo Colombo

Disclosures

Aliment Pharmacol Ther. 2021;53(10):1080-1089. 

In This Article

Abstract and Introduction

Abstract

Background: The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD).

Aims: To review the potential interaction of HCV and MAFLD.

Methods: We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD.

Results: In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV.

Conclusions: This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.

Introduction

The health, economic and societal burden of end-stage liver disease is immense. A recent estimate suggests that 844 million people have chronic liver disease, exceeding other major health problems such as cardiovascular disease (540 million), diabetes (422 million) and pulmonary disease (650 million).[1] Liver disease is projected to surpass ischaemic heart disease, with regard to years of working life lost.[2] The economic burden of end-stage liver disease is substantial, with direct annual costs estimated to be $2.5 billion and indirect costs as much as $10.6 billion in the United States.[3]

Although declining, chronic hepatitis C (CHC) is currently still one of the major aetiologies of cirrhosis and hepatocellular carcinoma (HCC) in the world.[4] It has been estimated that around 71 million individuals have CHC worldwide, with a prevalence rate of 1.0%.[4] The development of highly effective direct-acting antivirals (DAAs) for CHC encouraged the World Health Organization (WHO) to set a target to eliminate HCV infection globally by 2030, with the aim to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%.[5] DAAs can lead to sustained virological response (SVR) in more than 95% of patients, suggesting that these targets are achievable, particularly if they are supported by global political commitment. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease, HCC burden and dropout rate from the liver transplant waiting list.[6]

The various types of fatty liver disease led to a difficulty to define this disease condition by a single term.[7–9] A panel of international experts proposed a new definition for the diagnosis fatty liver diseases that is both comprehensive and simple, and is independent of other liver diseases. The evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus or evidence of metabolic dysregulation, constitute the diagnosis of metabolic-associated fatty liver disease (MAFLD)[7–9] which replaces to still common term non-alcoholic fatty liver disease (NAFLD). Not using "non alcoholic" allows including moderate alcohol consumption in the characterisation of such patients. Moderate ethanol consumption above "safe" levels is part of standard nutrition in many societies and may increase the risk to develop advanced liver disease. Some patients may have a dual aetiology fatty liver disease (concomitant MAFLD and other liver disease; ie alcoholic hepatitis).[10]

The decrease in CHC prevalence has been countered by a marked increase in the prevalence MAFLD, which is estimated to affect about a quarter of the global population.[11] This increase is fuelled by rising prevalence of obesity and type 2 diabetes, even among those who are non-obese.[12] MAFLD is on track to become the primary indicator for liver transplantation and HCC development, globally.[13,14] The burden of end-stage liver disease due to MAFLD is projected to increase by 200% to 300% over the next two decades across different regions worldwide.[15] Thus, although much progress has been made towards elimination of CHC,[16] the increasing burden of MAFLD among those cured of HCV could play a detrimental role and hinder this progress. Given this burden, consideration of the impact of MAFLD on viral hepatitis elimination should be a priority.

The interplay between MAFLD and CHC is very complex,[17] and is not fully characterised yet. According to the current guidelines of the American Association for the Study of Liver Diseases (AASLD),[18] the diagnosis of NAFLD requires a set of exclusion criteria, including "significant alcohol consumption, competing aetiologies for hepatic steatosis and coexisting causes of chronic liver disease". This combination of "negative" criteria, and relying on the exclusion of other liver diseases, including viral hepatitis for diagnosing NAFLD, represents a challenge for proper understanding of the interaction between the two diseases. This underscores the importance of the recent influential shift towards "positive" criteria for the diagnosis of MAFLD in the CHC population,[7–9] since overlooking MAFLD would likely not allow for the realisation of the full financial benefits, including any healthcare cost savings obtained through successful HCV treatment.

Clinicians working in the viral hepatitis field are becoming concerned about MAFLD being overlooked in patient populations and the impact of MAFLD on achieving the goals of elimination of viral hepatitis by 2030.[19] Therefore, an international expert group was assembled to review the interactions between MAFLD in patients achieving HCV cure and provide recommendations to help maintain the gained health and economic benefits after HCV eradication with DAA.

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