Patients with Sickle Cell Disease Show High Prevalence of Liver Complications

Konstantinos Manganas, PhD Candidate

credit: https://en-uoa-gr.academia.edu/

New research conducted across various Thalassemia and Sickle Cell Units in Greece highlighted the burden of chronic liver complications in individuals with Sickle Cell Disease (SCD).¹

The study aimed to identify the main predisposing factors for advanced liver fibrosis in individuals with SCD. The findings showed complications and cirrhosis as major causes of morbidity in patients with SCD, with implications for treatment and care.

Konstantinos Manganas, from the Thalassemia and Sickle Cell Unit, Hippokration General Hospital, and a team of investigators from various Thalassemia and Sickle Cell Units across the country conducted a comprehensive investigation involving 219 patients with SCD.

The team collected and analyzed data on the patients' history of liver-related disease complications, conducted laboratory tests, and used imaging analysis to assess liver function.

Prevalence of Advanced Liver Fibrosis:

Results revealed a concerning 13.6% of patients with SCD exhibited advanced liver fibrosis. The presence of liver fibrosis was significantly correlated with certain factors, including advanced age, male gender, cholelithiasis or gallstones, and elevated levels of LDH, γ-GT, INR, direct and indirect bilirubin.

For the analysis, patients were divided into 2 groups based on the presence or absence of advanced liver fibrosis (≥F3). Of the patients studied, 29 (13.6%) exhibited indications of advanced liver fibrosis, and 185 (86.4%) did not have indications of advanced fibrosis.

Factors significantly associated with advanced liver fibrosis included higher levels of AST, γ-GT, INR, LDH, direct and indirect bilirubin, lower levels of albumin, Hb, and platelet count, as well as higher Liver Iron Concentration (LIC) and ferritin levels.

The patient cohort consisted of 84 men (38.4%) and 135 women (61.6%), with a median age of 47 years (SD, 19 - 86 years).

The genotypes of the patients were characterized and reported:

• 181 patients had HbSβthal (82.6%)
• 33 had HbSS (15.1%)
• 2 had HbS/HbD (0.9%)
• 2 had HbS/Lepore (0.9%)
• 1 had HbSδβthal (0.5%)

Among HbSβthal patients, 115 were HbSβ+thal (63.5%), 32 were HbSβ0thal (17.7%), and data were insufficient for 34 patients (18.8%).

Investigators also observed a link between advanced liver fibrosis and specific medical occurrences. Patients with liver fibrosis had experienced significantly more episodes of liver crises and acute intrahepatic cholestasis.

However, the investigation exhibited no correlation between advanced liver fibrosis and right heart failure or previous viral hepatitis.

Of all patients, 108 (52.9%) had a history of cholelithiasis, while 2 patients (1.4%) had experienced an acute liver crisis, 1 patient (0.7%) had acute intrahepatic cholestasis, and 10 patients (7%) had 1 or more acute liver sequestration events in the past 5 years.

Investigators also observed 28 patients (15.7%) with ultrasound indications of liver cirrhosis, and 2 patients (1.4%) had portal hypertension. Echocardiographic evidence of right heart failure was found in 13 patients (6.6%), and 36 patients (26.7%) showed indications of pulmonary hypertension.

A noteworthy association between advanced liver fibrosis and the type and duration of transfusion therapy was demonstrated. Patients who were receiving a more intensive transfusion therapy for a longer period of time were more likely to show the presence of liver fibrosis.

More than half of patients (n = 129, 58.9%) were not on a regular transfusion program, while 90 patients (41.1%) were receiving regular transfusions or exchange transfusions for conditions such as secondary stroke prevention, acute chest syndrome (ACS) prevention, pulmonary hypertension, congestive heart failure, and renal failure.

The mean duration of transfusions in regularly transfused patients was 14.1 years (ranging from 1 - 70 years), with an average of 14.3 units of packed red blood cells transfused per year (ranging from 1 - 36 transfusions/year).

Furthermore,the study stated higher liver iron concentration levels were observed in patients with advanced liver fibrosis, indicating a secondary association with iron overload in these cases.

Liver complications and cirrhosis were primarily associated with intravascular hemolysis and vaso-occlusive crises (VOC) or phenomena–both processes play a crucial role in the development of liver complications among SCD patients.

Investigators suggested the study's findings have significant implications for the treatment and care of individuals with SCD. The high prevalence of liver complications and cirrhosis underscores the importance of regular liver function monitoring in SCD patients, particularly in those with identified risk factors such as advanced age, male gender, and cholelithiasis.

References:

1. Manganas K, Delicou S, Xydaki A, et al. Predisposing factors for advanced liver fibrosis in patients with sickle cell disease [published online ahead of print, 2023 Jul 12]. Br J Haematol. 2023;10.1111/bjh.18970. doi:10.1111/bjh.18970