Hepatobiliary complications in patients with sickle cell disease: A 30-year review of 1009 patients.

Background: Sickle cell disease (SCD) is the most common hemoglobinopathy. We aimed to identify the prevalence of hepatobiliary injury and its association with mortality in SCD.

Methods: Patients with SCD followed at a dedicated clinic at our tertiary center were retrospectively evaluated with descriptive statistics. Correlations between hepatobiliary complications and SCD complications were expressed as ORs. To evaluate mortality predictors, log-rank testing was used for univariate analysis and Cox proportional hazards for multivariable analysis, with time-dependent covariates for biochemistry.

Results: Between January 1990 and December 2020, 1009 patients with SCD were identified; 63.2% were HbSS. The median age at first clinic visit was 26.4 years (IQR: 18.9-37.1), 44.3% were male, and 62.6% were ever treated with hydroxyurea. The median follow-up was 4.8 years (IQR: 1.9-8.5); mortality was 8.9%. The most frequent hepatobiliary manifestations were cholelithiasis (n=431 [42.7%]) and iron overload (n=121; 12%). Chronic viral hepatitis was reported in only 18 patients. Twenty-nine patients (2.1%) had peak ALT> 2× upper limit of normal, 15 (2.3%) had peak ALP> 2× upper limit of normal, 97 (10.3%) had peak total bilirubin >103 μmol/L, (6.02 mg/dL), and 184 (18.2%) patients had elevated peak direct bilirubin. Hepatomegaly was reported in 37 patients (3.7%), while 24 patients (2.4%) were clinically cirrhotic. Five patients received a liver transplant. In an exploratory multivariate model, age (HR 1.08 [95% CI: 1.05-1.11]), ALT elevation (HR 1.52 [95% CI: 1.29-1.78]), and total bilirubin >103 μmol/L (HR 9.3 [95% CI: 3.95-21.9]) predicted mortality independently.

Conclusions: Hepatobiliary complications are common in patients with SCD and require vigilance for identification.