Screening for liver fibrosis in the general population: a call for action

Summary

Liver cirrhosis is one of the main causes of death and disability-adjusted life-years worldwide. Generally, cirrhosis develops after a long period of liver-cell injury that leads to the deposition of collagen, leading to progressive fibrosis and nodule formation in the liver tissue. Most patients are diagnosed in late stages when liver decompensation or liver cancer develops. The diagnosis is rarely made in early stages—when liver fibrosis is mild to moderate but cirrhosis is not yet established—because the disease is asymptomatic. No strategies for detection of liver fibrosis at these early stages have been developed, but therapies are more effective in early stages than late stages of chronic liver diseases, so enabling early detection is an important research topic. Non-invasive methods for assessing liver fibrosis have been developed, of which the most commonly used are transient elastography—which estimates liver fibrosis by measuring liver stiffness—and serum biomarkers of fibrosis. Studies have shown that 6–7% of the adult population without known liver disease have liver fibrosis, mostly associated with non-alcoholic fatty liver disease. These data suggest that programmes of screening for liver fibrosis in the general population should be assessed.

Introduction

Chronic liver diseases are very common worldwide and have become a major global health issue. Data from the Global Burden of Disease Study 2013¹ showed that cirrhosis is one of the main causes of death worldwide, both in men and women. Cirrhosis was estimated to account for 1 221 100 deaths globally in 2013, and is the 12th most common cause of death, accounting for 2·2% of all deaths worldwide.¹ Deaths due to cirrhosis increased by 46% between 1990 and 2013, indicating an increasing incidence of the disease. The number of deaths due to cirrhosis was close to the number due to tuberculosis (1 290 300), AIDS (1 341 000), and diabetes mellitus (1 299 400), and higher than that of other major diseases, such as malaria (854 600), colorectal cancer (771 100), and breast cancer (471 000). If deaths due to hepatocellular carcinoma—which mostly occurs with an underlying cirrhosis—are added to those of cirrhosis, the number of deaths increases to 2 039 100, becoming the fifth leading cause of death worldwide, accounting for 3·7% of all deaths in 2013.¹ Additionally, cirrhosis is one of the leading causes of hospital admissions because of the recurrent nature of its complications.2, 3 Therefore, cirrhosis represents a major health issue worldwide because of the high associated mortality and notable burden on health-care systems. However, despite its importance, liver cirrhosis has not received the required attention by policy makers, public opinion, and even physicians.

Cirrhosis is the final consequence of chronic liver disease, and can be caused by several factors, including hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol abuse, and metabolic syndrome, or a combination of these factors.⁴ Because these factors are common worldwide, chronic liver diseases are highly prevalent. The use of highly effective antiviral drugs is likely to dramatically reduce HCV infection; however, the other causes are at best predicted to remain steady, but will most likely increase. Epidemiological studies suggest that the incidence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly in many areas of the world, particularly associated with the epidemics of obesity and diabetes.⁵ Furthermore, the average alcohol consumption in the world increased from 2005 to 2010 and is expected to continue to increase until 2025. Therefore, the overall prevalence of cirrhosis is not expected to decrease markedly unless action is taken to diagnose and treat chronic liver diseases as early as possible.

The major histological consequence of chronic liver diseases is the unrelenting deposition of collagen fibres due to activation of hepatic stellate cells that causes progressive liver fibrosis and, eventually, cirrhosis.4, 6 Although this process occurs very slowly over decades, the disease is rarely diagnosed in the precirrhotic stage or in early cirrhosis because it is asymptomatic and thus patients do not seek medical attention. Diagnosis most commonly occurs once the disease has reached the later stages with decompensation of cirrhosis or when hepatocellular carcinoma develops. Liver transplantation is the only curative therapy for end-stage cirrhosis, and unfortunately can only be done in a minority of patients because of the small number of organs available.

Given the high prevalence and related mortality of cirrhosis in many countries, chronic liver diseases should ideally be diagnosed before cirrhosis develops or at the stage of early cirrhosis. This early diagnosis would allow identification of causal factors responsible for liver inflammation and subsequent application of specific targeted interventions (eg, antiviral therapy for HBV or HCV infection, psychosocial interventions for alcoholic liver disease, and lifestyle changes and treatment of diabetes and obesity for NAFLD).⁷ The elimination of the causative factor halts hepatic inflammation and leads to fibrosis regression.⁶ However, the identification of patients in early stages of chronic liver diseases raises two important questions that we discuss in this Viewpoint: are any reliable methods for early diagnosis available, and, if so, could these methods be used for screening in the general population?