|Year : 2014 | Volume
| Issue : 1 | Page : 11-14
Biochemical and ultrasound assessment of the liver in sickle cell anaemia patients in Zaria, Nigeria
Rasheed Yusuf1, Abdulaziz Hassan2, Aliyu Ahmadu Babadoko2, Philip Oluleke Ibinaiye3
1 Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
3 Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Web Publication||18-Sep-2014|
Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Sickle cell anemia (SCA) is frequently associated with liver disease. The constant state of hemolysis due to reduced red cell survival; and multiple blood transfusions, places these patients at risk hepatic sinusoidal congestion, viral hepatitis, cholestasis, and hemosiderosis, all of which may contribute to the development of liver disease.
Objective: The aim was to assess the pattern of biochemical liver function tests and their relationship with liver size in steady state adult SCA patients in Zaria, North-West, Nigeria.
Materials and Methods: Seventy-one adult SCA patients in steady state and 20 hemoglobin AA controls were enrolled into the study. Liver function tests were carried out and liver spans assessed using B-mode ultrasound scan in all subjects.
Results: The serum bilirubin, aspartate transaminase (AST) and AST/alanine transaminase (ALT) ratio were significantly higher in SCA patients than in controls, with P values of 0.04, <0.001, and <0.001 respectively. Thirty-four (48%) SCA patients had AST/ALT ratio of >2. Hepatomegaly was present in 67/71 (94%) of the patients, and absent in the controls. The liver span was significantly greater in SCA patients (P < 0.001). There were no significant difference in the mean values of ALT, alkaline phosphatase (ALP), total protein and albumin. There was no correlation between the liver span and the biochemical parameters.
Conclusion: Steady state SCA patients in Ahmadu Bello University Teaching Hospital, Zaria, have hepatomegaly associated with minimal elevation of ALT and ALP. There was no correlation between the liver span and the biochemical parameters. It is advisable that liver function tests and liver ultrasound scan be interpreted with caution in these patients.
Keywords: Liver function tests, liver ultrasound scan, sickle cell anemia
|How to cite this article:|
Yusuf R, Hassan A, Babadoko AA, Ibinaiye PO. Biochemical and ultrasound assessment of the liver in sickle cell anaemia patients in Zaria, Nigeria. Ann Nigerian Med 2014;8:11-4
|How to cite this URL:|
Yusuf R, Hassan A, Babadoko AA, Ibinaiye PO. Biochemical and ultrasound assessment of the liver in sickle cell anaemia patients in Zaria, Nigeria. Ann Nigerian Med [serial online] 2014 [cited 2021 Apr 18];8:11-4. Available from: https://www.anmjournal.com/text.asp?2014/8/1/11/141023
| Introduction|| |
Aickle cell hepatopathy encompasses a range of hepatic pathology arising from a wide variety of insults to the liver in patients with sickle cell disease.  The incidence of liver disease in sickle cell disorders is difficult to ascertain despite being a component of the multiorgan failure that occurs in sickle cell disease.  This is because dysfunction of the liver in sickle cell disease is multifactorial. 
The hepatic complications of sickle cell anemia (SCA) can be classified into the following: disorders related to hemolysis, the problems of anemia and transfusion management, the consequences of sickling and vaso-occlusions, and defects unrelated to sickle cell disorder.  The clinical manifestation of the different causes of liver failure is also similar and interrelated, thus making the pathophysiology complex. Besides, enlargement of the liver does not connote disease, so also, a normal size liver may be diseased. 
Raised bilirubin levels, predominantly unconjugated, are universal in sickle cell patients due to chronic hemolysis.  Elevation of the different liver enzymes correlates with the different categories; hemolysis raises plasma aspartate transaminase (AST), while plasma alanine transaminase (ALT) levels more accurately reflects hepatocyte injury.  Elevations in serum alkaline phosphatase (ALP) is commonly seen in patients with SCA, particularly during pain crises. Studies, however, suggest that bone ALP is the major enzyme fraction contributing to this increase. 
Abnormal liver function tests are common in patients with SCA, even in the absence of liver disease.  This study therefore attempt to unveil the pattern of biochemical liver function tests and their relationship with liver size obtained on ultrasound scan in steady state adult SCA patients in Zaria, North-West, Nigeria.
| Materials and Methods|| |
This was a cross-sectional study of adult SCA patients in steady state conducted at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, North-West, Nigeria. The study was approved by the Ethical and Scientific Committee of the hospital and was carried out between May and July 2010. Patients from the adult hematology clinic that fulfilled the inclusion criteria and gave informed consent during the study period were recruited. Patients who drink alcohol, smokes cigarette and those with chronic complications of SCA were excluded. Seventy one SCA subjects (39 females and 32 males) and 20 healthy controls (10 females and 10 males) from the community were recruited into the study. Subjects underwent complete history, physical examination, liver function tests, hemoglobin electrophoresis and abdominal ultrasound scan. Biochemical parameters (AST, ALT, and ALP), AST/ALT ratio, total bilirubin, total protein and albumin) were determined by SELECTRA XL ® chemistry autoanalyser with analysis in batches. Each assay was validated using commercial quality control samples and standards.
All subjects were scanned by a consultant radiologist using B-mode ultrasonography with Aloka product (mode SSD-3500, Hitachi Aloka medical limited, Tokyo, Japan) ultrasound diagnostic equipment, with a variable frequency probe at 2-5 MHz or 5-10 MHz. Examination was performed with the patient in supine, right side, or left side position to obtain an optimal view. Measurements of the liver span were performed in all subjects along the long axis of the right lobe. Hepatomegaly was defined as long axis of the organ longer than 155 mm. 
Data obtained were analyzed using Statistical Package for Social Sciences (SPSS Inc., Chicago, USA) 15.0 for windows. Student's t-test was used to compare means of variables between patients and controls while Pearson's linear correlation analysis was used to test significance of association between liver span and biochemical parameters. P ≤ 0.05 (P ≤ 0.05) was considered as statistically significant.
| Results|| |
The mean age of the SCA patients was 23.22 ± 5.35 years, while that of the control group was 22.70 ± 1.22 years. Of the 71 sickle cell subjects, 39 (54.9%) were females; while of the 20 controls, 10 (50.0%) were females. None of the study subjects had a previous history suggestive of liver diseases. All the study subjects were hemoglobin SS homozygotes (SCA), while all the controls were hemoglobin AA homozygotes by alkaline hemoglobin electrophoresis. There was no history of previous blood transfusion in the control subjects.
The biochemical and ultrasound scan results are presented in [Table 1]. The serum bilirubin, AST and AST/ALT ratio (De Ritis ratio) were significantly higher in SCA patients than in controls, with P values of 0.04, <0.001, and <0.001 respectively. There were no significant difference in the mean values of ALT, ALP, total protein, and albumin. Thirty-four (48%) of the patients had AST/ALT ratio of >2.
|Table 1: Liver function tests values in SCA patients and controls (mean ± SD)|
Click here to view
[Table 2] shows the patterns of liver function tests in the study patients. Reference ranges for Zaria are AST (5-22 IU/L), ALT (16-40 IU/L) and ALP (21-92 IU/L). Elevated levels of AST, ALT and ALP were observed in 94.4%, 2.8%, and 31% of patients, respectively. Predominant unconjugated hyperbilirubinemia was present in 16% of the patients. None of the controls had elevated liver enzymes.
Ultrasound scan of the liver revealed hepatomegaly in 67/71 (94%) of the patients, while none of the controls had enlarged liver. The liver span was statistically significantly greater than in controls (P < 0.001). There was no correlation between the liver span and the biochemical parameters. A bright liver (hyper-echogenic liver on ultrasound scan), which may be indicative of hemosiderin deposit was observed in 11/71 (14.9%) of the patients with hepatomegaly.
| Discussion|| |
The findings of this study showed a significantly higher serum total bilirubin, AST and AST/ALT ratio (De Ritis ratio) in SCA patients in steady state when compared with the controls. Other biochemical parameters showed no statistically significant difference. The higher serum total bilirubin could be due to chronic hemolysis and/or ineffective erythropoiesis, which characterize the disease. Hemolysis raises serum AST level, and thus the increased level observed in SCA patients. The above findings are in agreement with previous finding by Johnson et al. and also supported by observation in the present study of elevated level of AST in 94.4% as against elevated level of ALT (better marker of hepatocytes injury compared with AST) in only 2.8%.
De Ritis ratio, which is used to determine hepatic necrosis, is statistically significantly higher in the patients than controls. This is most likely as a result of elevated level of AST found in majority of the patients which may be due to excessive hemolysis as reported in previous studies. ,
Although there was no statistically significant difference in the mean values of ALP in studied patients and controls, 31% of the SCA patients had elevated values. No significant association was found between the ALP values and liver size, and this is consistent with findings of previous studies by Kotila et al. and Brody et al.  This finding suggests that liver pathology may not account solely for the elevation of this enzyme. A similar study by Brody et al. had identified bone ALP as the principal enzyme fraction that increases during sickle cell crises, and there also appears to be concordance between crisis severity, serum levels of ALP and isoenzymes patterns. These abnormalities could also be detected even when the patients are asymptomatic. 
The findings in this study is contrary to that of Akuyam et al., who in a study in 2007 found statistically significant higher values of AST, ALT, ALP, total bilirubin and albumin in the SCA patients studied.  The findings in the present study may be as a result of improved standard of care giving to SCA patients in ABUTH, Zaria; health education, transfusion regimens, and new therapeutic modalities or options such as hydroxyurea. An establishment of a day care clinic and the subsidy of patients' drugs and investigations may have also contributed. All these subsequently improve their clinic attendance and better health status.
There was no evidence to support the fact that the liver enlargement seen in 94% of the patients is due solely to hepatic disease, because abnormality of ALT which is specific for hepatic injury was noted in only 2.8% of the patients, and there was no association between liver enzymes and liver size. This is similar to findings by Kotila et al. in which 77% of their patients had hepatomegaly, but only 19% had abnormality of ALT,  and the findings by Gόrkan et al. in which all their patients had hepatomegaly detected by both physical examination and abdominal ultrasonography.  Green et al. previously suggested that hepatomegaly, which is frequently seen in patients with SCD, is the result of intrasinusoidal sickling and engorgement of Kupffer cells.  The observations in this study suggest that these morphological findings are major contributing factors for the existence of hepatomegaly in patients with SCD. However, those morphologic findings do not necessarily cause hepatic dysfunction. 
Bright liver was found in 14.9% of the patients in the current study. Several features of liver histology in patients with SCD may contribute to the bright liver. These include hemosiderin pigment, periportal fibrosis, and distension of sinusoids with sickle cell.  These were, however, not assessed in this study.
| Conclusion|| |
The majority of steady state SCA patients in Zaria have hepatomegaly associated with minimal elevation of ALT and ALP. It was also noted that there was no correlation between the liver span and the biochemical parameters. Thus, it is advisable that liver function tests and liver ultrasound scan be interpreted with caution in patients with SCA.
| References|| |
|1.||Banerjee S, Owen C, Chopra S. Sickle cell hepatopathy. Hepatology 2001;33:1021-8. |
|2.||Hassell KL, Eckman JR, Lane PA. Acute multiorgan failure syndrome: A potentially catastrophic complication of severe sickle cell pain episodes. Am J Med 1994;96:155-62. |
|3.||Meshikhes AW, al-Faraj AA. Sickle cell disease and the general surgeon. J R Coll Surg Edinb 1998;43:73-9. |
|4.||Kotila T, Adedapo K, Adedapo A, Oluwasola O, Fakunle E, Brown B. Liver dysfunction in steady state sickle cell disease. Ann Hepatol 2005;4:261-3. |
|5.||Mohamed AO, Jansson A, Ronquist G. Increased activity of 5' nucleotidase in serum of patients with sickle cell anaemia. Scand J Clin Lab Invest 1993;53:701-4. |
|6.||Dick R, Watkinson A. The liver and spleen. In: Sutton D, editor. Textbook of Radiology and Imaging. 7 th ed. New York: Elsevier; 2002. p. 737-86. |
|7.||Johnson CS, Omata M, Tong MJ, Simmons JF Jr, Weiner J, Tatter D. Liver involvement in sickle cell disease. Medicine (Baltimore) 1985;64:349-56. |
|8.||Sheehy TW. Sickle cell hepatopathy. South Med J 1977;70:533-8. |
|9.||Schubert TT. Hepatobiliary system in sickle cell disease. Gastroenterology 1986;90:2013-21. |
|10.||Brody JI, Ryan WN, Haidar MA. Serum alkaline phosphatase isoenzymes in sickle cell anemia. JAMA 1975;232:738-41. |
|11.||Akuyam AS, Bamidele AS, Aminu SM, Aliyu IS, Muktar HM, Mamman AI. Liver function tests profile of sickle cell anaemia patients in steady state of health: Zaria experience. Borno Med J 2007;4:1-6. |
|12.||Gürkan E, Ergun Y, Zorludemir S, Baºlamiºli F, Koçak R. Liver involvement in sickle cell disease. Turk J Gastroenterol 2005;16:194-8. |
|13.||Green TW, Conley CL, Berthrong M. The liver in sickle cell anemia. Bull Johns Hopkins Hosp 1953;92:99-127. |
|14.||Ahmed S, Shahid RK, Russo LA. Unusual causes of abdominal pain: Sickle cell anemia. Best Pract Res Clin Gastroenterol 2005;19:297-310. |
[Table 1], [Table 2]