Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study

Abstract

Background: Persons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances.

Methods: Data was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI).

Results: At baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement.

Conclusions: More than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

Keywords: Chronic liver disease; Elastography; Hepatitis C; Injecting drug use; Liver stiffness measurement; Opioid agonist treatment; Prospective cohort; Steatotic liver disease; Substance use disorder.

Fig. 1

Overview of the recruitment and inclusion of participants in the study. The figure indicates which treatment facilities the participants were recuited from and the number of persons in the target population. The figure further indicates the number of participants with one or more elastographies

Fig. 2

Distribution of liver stiffness according to age, HCV status, and sex. The figure indicates how the increased risk of liver disease, indicated by liver stiffness ≥ 10 kPa, is distributed between age groups, HCV infection status, and sex. The Pearson χ² test indicates that there were significant differences between age groups (χ² = 33.8, p < 0.001) and by HCV infection status (χ² = 9.4, p < 0.002), but not between females and males (χ² = 3.1, p < 0.078)

Fig. 3

Distribution of liver stiffness measurements and its changes among the 676 patients included in the study. The red line indicates the baseline measurements sorted in incremental order. Spikes away from the red line indicate the change in liver stiffness from the first to the last measurement measured with elastography (in kPa). The black dashed line at 10.0 kPa indicates liver stiffness suggestive of compensated advanced chronic liver disease, whereas the black dashed line at 15.0 kPa indicates the threshold for liver stiffness highly suggestive of compensated advanced chronic liver disease such as liver fibrosis or cirrhosis [27]