Lupine Publishers| Journal of Gastroenterology and Hepatology
Abstract
Background: Metabolic bone disorders are frequent in patients with cirrhosis. These two conditions are usually misdiagnosed in Sub-Saharan Africa before the onset of complications. A full evaluation of metabolic bone disorders in patients with liver cirrhosis is difficult in our milieu and osteodensitometry is rarely available. In this preliminary study, we sought to determine the necessity of a cost-effective method, the Nordin’s Index, in the evaluation of osteoporosis in patients with liver cirrhosis.
Methods: This was a prospective cross-sectional study from January to May 2017 in Yaoundé. We compared the data of 19 patients (15 men, 4 women) with post viral liver cirrhosis and 17 controls (13 men, 4 women) paired with age, gender and body mass index (BMI). Data collected included vitamin D levels, serum and urine concentrations of calcium and phosphorus, Nordin’s Index and results of the bone mineral density using an x-ray absorptiometry scan. Statistical analysis was performed using the software SPSS 21. A p value of less than 0.05 was considered to be statistically significant.
Results: The mean age of patients was 38 ±15 years, with a mean BMI of 25 ±8 kg/m². Three of the four women were on menopause. Etiologies of cirrhosis were viral hepatitis B (8 patients), viral hepatitis B and D coinfection (7 patients), and viral hepatitis C (4 patients). The median duration of cirrhosis was 19 [8; 48] months, and 14 patients were classified grade A in Child Pugh classification. There was no statistical difference in the serum and urine concentrations of calcium and phosphorus. Osteoporosis was more frequent in cirrhosis (31.6% versus 11.8%, p<0.05). Nordin’s Index was significantly elevated in patients with cirrhosis compared to controls (0.12 [0.06; 0.13] mg/mg, versus 0.03 [0.01; 0.08] mg/mg, p<0.05), and in patients with cirrhosis associated to osteoporosis compared to those without (0.13 [0.09; 0.13] mg/mg versus 0.07 [0.03; 0.08] mg/mg, p<0.05). Vitamin D deficiency was more observed in controls (13/17 versus 7/19, p<0.05). Factors associated with osteoporosis were disease duration, elevated Nordin’s Index and elevated serum level of transaminases.
Conclusion: The Nordin’s Index, a simple and inexpensive tool for exploration of the phosphocalcic metabolism, could be useful for the evaluation of osteoporosis during viral cirrhosis. However, its performance has to be evaluated in a larger sample.
Keywords: Cirrhosis, chronic viral hepatitis, osteoporosis, Nordin’s Index, Vitamin D.
Abbreviations: ALAT: Alanine Aminotransferase; ALP: Alkaline Phosphate; ASAT: Aspartate Aminotransferase, BMD: Body Mass Density; GGT: Gamma Gluthamyl Transferase
Introduction
Cirrhosis is the outcome of most chronic liver diseases. It
remains a major public health problem in Sub-Saharan Africa
and particularly in Cameroon, where chronic viral hepatitis is
highly endemic [1-3]. In fact, sixty percent of cirrhosis in Africa
are attributable to viral hepatitis B and C [4]. In Cameroon,
70.9% of cirrhosis cases are due to chronic viral hepatitis B and
25.5% to chronic viral hepatitis C [5]. The hallmark of cirrhosis is
hepatocellular insufficiency and portal hypertension, resulting in
impaired liver function and subsequent systemic abnormalities.
Bone damage is one of the systemic abnormalities frequently
seen in cirrhosis, regardless of etiology, and is known as hepatic
osteodystrophy [6].
Hepatic osteodystrophy is a combination of osteoporosis and
osteomalacia, the latter being rare during cirrhosis [6]. According
to the World Health Organization (WHO), osteoporosis is a diffuse
disease of the skeleton, characterized by a decrease in bone mass
and an alteration of the micro-architecture of bone tissue, leading
to increased bone fragility and an increased risk of fractures [7]. Its
pathogenesis during cirrhosis is complex and leads to an increase in
bone resorption by osteoclasts to the detriment of its formation by
osteoblasts [8]. The prevalence of osteoporosis during cirrhosis is
between 12% and 55% [9]. In Africa, more precisely in the Maghreb
region, it has been estimated to 28.26% [10]. Osteoporosis is
almost asymptomatic until complications. It is a real public health
problem as it causes low energy fractures in more than 40% of
cases, affecting the morbidity and quality of life of patients with
cirrhosis [8]. Several factors are associated with the occurrence of
osteoporosis during cirrhosis, including vitamin D deficiency with
a prevalence of 32% in Europe and 32.6% in Africa during cirrhosis
[10,11]; Elevated Child and Pugh Score, duration of disease, etiology
of cirrhosis, low body mass index, with some controversy in the
literature [12].
Considering the risk of osteoporosis being high during cirrhosis,
it is necessary to have an evaluation of bone mineral density in
these patients [13,14]. However, this is rare in our context because
of the cost and accessibility of this examination. With the absence of
hepatic transplantation in our environment to cure cirrhosis, there
is a long duration of cirrhosis and, therefore, an increased risk of
complications including osteoporosis. It is therefore important to
use simple and inexpensive tools to make the diagnosis or at least
to detect high-risk subjects. Nordin’s Index is calculated by the
calciuria/creatinuria ratio. It is an old marker of bone resorption,
which correlates with post-menopausal osteoporosis and its risk
of fracture [15,16]. However, its usefulness in cirrhosis especially
post viral has been little studied to the best of our knowledge. In
this study, we sought to determine the utility of Nordin’s Index as
a cost-effective method in the evaluation of osteoporosis in people
suffering from post-viral cirrhosis in a highly endemic area for
chronic viral hepatitis and limited access to bone mineral density
assessment.
Patients and Methods
Study design
The study used a cross sectional design with a prospective data collection.
Study setting
This study took place from January to May 2017 at the Yaoundé Central Hospital and Cathedral Medical Centre (CMC) at Yaoundé, where the participants were recruited. Laboratory analysis were conducted at the University Hospital Centre of Yaoundé. Bone mineral density measurements were carried out at the Autonomous Centre for Radiology and Medical Imaging (CARIM) at Yaoundé.
Participants
The sample was made up of 19 adult volunteers (15 men and
4 women) followed for a cirrhosis of viral cause (chronic viral
hepatitis B, C, and D). They were matched with 17 adult volunteers
(13 men and 4 women) without any chronic or acute disease/
condition, paired with age (±2 years), gender and body mass index
(BMI; ±2 kg/m²). The diagnosis of liver cirrhosis was based on
clinical and biological signs of portal hypertension and chronic
liver failure, ultrasonographic signs of chronic liver disease and
endoscopic signs of portal hypertension. Ultrasonographic signs
included irregular liver outline, heterogeneous echo structure,
dysmorphic liver, enlarged portal vein and presence of collateral
venous circulations.
The controls were recruited from among the patients’
caregivers to ensure equal exposure to environmental and
nutritional factors that may contribute to osteoporosis. We did not
include any participants who presented pathologies with known
repercussions on bone and/or phosphocalcic metabolism, such as:
chronic renal disease, thyroid and parathyroid disorders, Cushing
Syndrome, diabetes, HIV infection and cancer. We did not include
participants receiving treatment with known effects on bone and/
or calcium phosphorus metabolism such as: hormone replacement
therapy, biphosphonates, calcium, vitamin D, corticosteroids,
antimetabolites, anticoagulants, anticonvulsants, thyroxine.
Pregnant women instead of women with amenorrhea, participants
with diabetes, tobacco and alcohol consumers were not included.
Sample size calculation
The sample size was estimated using the formula in Whitley et al. to compare proportions between groups [17]. The parameters used for the calculation of the standardized difference were derived from the study of Goral et al [18]. They found a mean T-score of -1.6 SD in patients with cirrhosis and -0.25 SD in controls, with a standard deviation of 1.3 SD. In our study, the level of significance was set at p 0.05 and the power at 80%. The minimum sample per group was 15.
Procedure
Ethical considerations
We obtained research authorizations in the selected health care facilities and the approval of the Institutional Review Board of the Faculty of Medicine and Biomedical Sciences. All the participants read and signed an informed consent form.
Clinical data
Sociodemographic (age, gender) and clinical data were collected through a questionnaire. Clinical variables were anthropometric parameters (weight and height) for BMI calculation, the history of cirrhosis (duration, etiology, complications, current Child and Pugh’s Score, treatment), suggestive signs of osteoporosis and its complications (history of pathological and or low energy fracture), comorbidities, menopause for women and its duration, and family history of osteoporosis.
Laboratory Analysis
For laboratory analysis, 10 mL of peripheral venous blood sample was collected from each participant after eight hours of fasting. The blood samples were centrifuged for 5 minutes at 3000 rpm using the Humax 14K Germany centrifuge. 500μl of serum was then extracted for the determination of calcium (mg/L), phosphorus (mg/L), albumin (g/L) by colorimetric method and for the determination of creatinine (mg/l), total alkaline phosphatase (U/L), transaminase (Aspartate amino transferase (ASAT), Alanine amino transferase (ALAT), in U/L), gamma gluthamyl transferase (GGT, U/L) by kinetic method, using the Mindray model BS 120 spectrophotometer. The remaining serum was stored at -20° Celsius and used to determine 25(OH) vitamin D (ng/mL) levels by ELISA using the BioTek EL×800 ELISA chain. Serum creatinine was used to estimate the glomerular filtration rate using four parameters’ MDRD formula in mL/min for 1.72m². The measured calcemia was corrected using albuminemia. Hypercalcemia was defined for a corrected Calcemia > 104 mg/L, while Hypocalcemia was defined below 81 mg/L [19]. Hyperphosphatemia was defined as blood phosphorus > 50 mg/L in adults while hypophosphatemia was defined below 25 mg/L [19]. Vitamin D Status was assessed according to the classification of Holick et al [20].
Laboratory Analysis
After consumption of 200 ml of low calcium water (Volvic® type: Ca<10 mg) in a fasting individual with a previously empty bladder, calciuria and creatininuria was measured on the urine collected 2 hours later. Nordin’s Index was calculated: calciuria/ creatininuria (mg/mg). The normal value of the Nordin’s Index is lower than 0.11 mg/mg. An increase in the index indicates hyperresorption of bone. Calcium, phosphorus and creatinine in urine were determined using the same methods as in the plasma.
Bone Mineral Density (BMD)
Bone mineral density was measured by biphotonic X-ray absorptiometry scan using the Hitachi® lunar prodigy DXA system, with 37 Micro SieVert (μSV) dose per measurement site. Bone mineral density was measured at the lumbar spine, the neck of the left femur and the distal end of the left radius. Data on bone mineral density were expressed in g/cm², T-score and Z-score. Osteoporosis was defined as T-score <-2.5 for patients aged 50 years and older or a Z-score <-2 for patients under 50 years of age for measurement of the lumbar spine, femoral neck or distal end of the radius [21].
Statistical analysis
Statistical analysis was performed using SPSS version 21.0. Quantitative variables were expressed as mean ± standard deviation or median and interquartile range [25th and 75th quartiles]. Qualitative variables were expressed as effectives and proportions. The Mann-Whitney test was used to compare the means, while medians were compare using the Median’s test. Fisher Exact Test was used to compare proportions. We searched for associations between continuous variables and bone mineral density on various sites by calculating the Pearson’s Correlation Coefficient to determine the factors associated with the decrease in BMD. For all the tests, the statistical significance level was set at 0.05.
Results
Clinical characteristics of the study samples
The mean age of patients was 38.6 ±15.9 years, while that of controls was 37.8 ±15.9 years (p>0.05). Participants’ ages ranged from 23 to 73 years. There were respectively 2/4 and 2/4 women on menopause in the patients and control groups. Between cases and controls, there was no statistical difference in body mass index (p>0.05) (Table 1). The median duration of cirrhosis was 19 months, range from one to 120 months. The causes of liver cirrhosis were chronic viral hepatitis B (42%), hepatitis C (31%), and B-delta (37%). There was no coinfection with viral hepatitis B and C. Most of the cases were classified on stage A (n=14), while 3 and 2 cases were respectively on-stage B and C in Child and Pugh classification.
Read More About Lupine Publishers Journal of Gastroenterology and Hepatology Please Click on Below Link: https://currenttrendsingastroenterology.blogspot.com/
No comments:
Post a Comment
Note: only a member of this blog may post a comment.