Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.
Egypt has the highest prevalence of HCV infection in the world, estimated nationally at 14.7% [
T4 and T3 regulate the basal metabolic rate (BMR) of all cells, including hepatocytes, and thereby modulate hepatic function. The liver metabolizes the THs and regulates their systemic endocrine effects. Thyroid diseases may perturb liver function; liver disease modulates thyroid hormone metabolism; and a variety of systemic diseases affect both organs [
60 patients with chronic hepatitis C (CHC) infection were selected for the study; they were followed up at outpatient clinics at Beni Suef University Hospital and Beni Suef General Hospital . We excluded the following patient from study; patients who tested positive for serum HBs Ag, patients suffering from previously known thyroid disease, patients who were currently under treatment or were previously treated with thyroid stimulating/ inhibiting agents, patients who were currently under treatment or were previously treated with interferon therapy, patients on medications that could affect the study outcome including Carbamazepine, Phenobarbitone, Phenytoin, Salicylates and Nonsteroidal anti-inflammatory drugs (NSAIDs) and patients with a history of alcohol consumption in the previous six months. The patients who met these criteria were divided into two groups: Group I: 15 patients with CHC infection without liver cirrhosis and Group II: 45 patients with CHC infection with liver cirrhosis. Group II was classified according to the Child-Turcotte-Pugh scoring system into Child A (15 patients) , Child B (15 patients) , and Child C (15 patients) .
All the patients in the study were subjected to the following; informed consent; history taking such as history of HCV infection or thyroid disorder, treatment or history of IFN therapy, or history of other diseases or other special habits; clinical assessment including symptoms and signs of hepatic decompensation (e.g., encephalopathy, ascites and jaundice or manifestations of thyroid disorder or other manifestations in other systems). Investigations including abdominal ultrasound, laboratory tests were performed and included: liver function tests (aspartate aminotransferase or AST, ALT, serum albumin, serum bilirubin, prothrombin time and concentration, INR) , serum anti-HCV antibody, HCV RNA PCR, serum HBs-Ag, complete blood count, thyroid functions (FT3, FT4, and TSH) , using the enzyme linked immunosorbent assay (ELISA) kit provided by ACCU-Bind ELISA kit, USA.
All statistical calculations were done by computer using the Microsoft Excel 2010 program and the Statistical Package for the Social Sciences (SPSS) software version 17 for Microsoft Windows. The following tests were used; descriptive analysis of the results in the form of percentage distribution for qualitative data and calculation of minimum, maximum, mean, and standard deviation for quantitative data, cross tabulation test: for comparison between percentage values, student’s t-test: for comparison between means of two groups, the Chi-square test: used to test the statistical significance of differences in a classification system (one-way classification) or the relationship between two classification systems (two-way classification) , Fisher’s exact test: used to calculate an exact P-value for a 2 × 2 frequency table with a small number of expected frequencies, for which the Chisquare test is not appropriate. Mann-Whitney U test for two independent samples: a nonparametric test for a between- subjects design using two levels of an independent variable and scores that are measured at least at the ordinal level.
Regarding age and gender, there were no statistically significant differences between the non-cirrhotic and the cirrhotic groups, as shown in
Regarding the thyroid profile, there was a statistical highly significant difference in TSH and a statistically significant difference in FT3 and FT4 between the groups, as shown in
Regarding age, there was a statistically significant difference in age between patients in Child A, B, and C; between patients in Child A and C; and between patients in Child B and C. However, there was no statistically significant difference between patients in Child A and B,
P: Comparison between Child A, B, and C;
P1: Comparison between Child A and Child B;
P2: Comparison between Child A and Child C;
P3: Comparison between Child B and Child C.
Variables | Non-cirrhotic group | Cirrhotic group | ||||
---|---|---|---|---|---|---|
Age (years) | ||||||
X ± SD | 47.5 ± 8.8 | 51.8 ± 8.2 | t | P | ||
Range | 27 - 60 | 33 - 65 | 2.1 | 0.089 | ||
Gender | N | % | N | % | X2 | P |
Male | 9 | 60 | 30 | 66.7 | 0.22 | 0.639 |
Female | 6 | 40 | 15 | 33.3 |
Variables | Child A | Child B | Child C | F | P | |||
---|---|---|---|---|---|---|---|---|
Age (years) | 3.7 | P = 0.036* P1 = 0.852 P2 = 0.031* P3 = 0.020* | ||||||
X ± SD | 49.9 ± 8.5 | 49.3 ± 8.9 | 56.2 ± 5 | |||||
Range | 33 - 60 | 38 - 64 | 46 - 65 | |||||
Gender | N | % | N | % | N | % | X2 0.0 | 1 |
Male | 10 | 66.7 | 10 | 66.7 | 10 | 66.7 | ||
Female | 5 | 33.3 | 5 | 33.3 | 5 | 33.3 |
Regarding the thyroid profile FT3, FT4, and TSH there was a statistically significant difference between the cirrhotic groups, except between Child A and Child B as shown in
Regarding the correlation between the thyroid profile and other variables, FT3 showed a statistically significant positive correlation with platelets, albumin, and PC% and an inverse correlation with ALT and T. bilirubin. FT4 showed a significant positive correlation with PC% and an inverse correlation with T. bilirubin. TSH showed a significant positive correlation with ALT and T. bilirubin, and an inverse correlation with platelets, albumin, and PC%, as shown in
Child A | Child B | Child C | F | P | |
---|---|---|---|---|---|
FT3 | 6.3 | P = 0.004** P1 = 0.078 P2 = 0.001** P3 = 0.048* | |||
X ± SD | 2.5 ± 0.6 | 1.9 ± 1.0 | 1.4 ± 1.0 | ||
Range | 1.4 - 3.6 | 0.1 - 3.3 | 0.2 - 3.7 | ||
FT4 | 4.1 | P = 0.023* P1 = 0.420 P2 = 0.046* P3 = 0.008** | |||
X ± SD | 1.1 ± 0.4 | 1.3 ± 0.9 | 0.7 ± 0.4 | ||
Range | 0.6 - 2.1 | 0.3 - 2.6 | 0.2 - 1.9 | ||
TSH | 17.7 | P = ˂0.001** P1 = 0.529 P2 = 0.001** P3 = 0.001** | |||
X ± SD | 1.5 ± 1.2 | 3.3 ± 3.1 | 18.1 ± 14.3 | ||
Range | 0.3 - 4.3 | 0.3 - 8.6 | 0.9 - 45.7 | ||
Median | 0.6 | 1.9 | 21.5 |
FT3 | FT4 | TSH | ||||
---|---|---|---|---|---|---|
r | P-value | r | P-value | r | P-value | |
TLC | 0.01 | 0.909 | 0.01 | 0.965 | 0.1 | 0.489 |
Platelets | 0.4 | 0.005** | 0.2 | 0.291 | −0.5 | 0.001** |
ALT | −0.3 | 0.037* | −0.2 | 0.211 | 0.5 | 0.001** |
Albumin | 0.5 | 0.001** | 0.2 | 0.133 | −0.6 | 0.001** |
T. bilirubin | −0.4 | 0.006** | −0.4 | 0.013* | 0.7 | 0.001** |
PC% | 0.5 | 0.001** | 0.4 | 0.004** | −0.7 | 0.001** |
The liver plays an important role in the metabolism of THs, as it is the most important organ in the peripheral conversion of T4 to T3 by D1 [
T4 and T3 regulate the BMR of all cells, including hepatocytes, and thereby modulate hepatic function. The liver metabolizes the THs and regulates their systemic endocrine effects. TD may perturb liver function; liver disease modulates thyroid hormone metabolism; and a variety of systemic diseases affect both organs [
In our study the total number of patients was 60 patients; the patients were divided into two groups: Group I (15 patients) had CHC infection without liver cirrhosis (non-cirrhotic group); Group II (45 patients) had CHC infection with liver cirrhosis (cirrhotic group) . Group II (cirrhotic group) was further subdivided according to the CTP scoring system into Child A (15 patients) , Child B (15 patients) and Child C (15 patients) .
In the statistical analysis, Group I (non-cirrhotic group) was compared with Group II (cirrhotic group) ; also patients classified as Child A, B and C was compared within the cirrhotic group.
In the present study, when the age and gender of patients in Group I and Group II were compared, there were no statistically significant differences between the two groups.
The results of the present study showed a statistically significant decrease in FT3 level in patients with CHC with cirrhosis (Group II) , when compared to patients with CHC without cirrhosis (Group I) (P = 0.039).
To date, studies and reports unanimously agree that patients with liver cirrhosis have low serum total T3 and FT3.
The present study is in agreement with [
The results of the present study showed a statistically significant decrease in FT4 level in patients with CHC with cirrhosis (Group II) when compared to patients with CHC without cirrhosis (Group I) (P = 0.019).
This is in agreement with [
On the other hand, this disagrees with [
The results of the present study showed a highly significant statistical increase in the TSH level in patients with CHC with cirrhosis (Group II) when compared to patients with CHC without cirrhosis (Group I) (P = 0.001).
This is in agreement with [
However, it disagrees with [
The results of the present study showed that there was a statistically significant difference in the FT3 level between the groups (except between Child A and B) as follows: Child A, B, and C (P = 0.004); Child A and B (P = 0.078); Child A and C (P = 0.001); and Child B and C (P = 0.048). The lack of a statistically significant difference between Child A and B was probably due to the fact that the patients were in the early stages of Child A and Child B.
On comparing the mean serum levels of FT3 in Child A, B, and C, the lowest levels were among the Child C group (1.4 ± 1.0), followed by the Child B group (1.9 ± 1.0), while the Child A group was within the normal range (2.5 ± 0.6). This is in agreement with [
On comparing the mean serum level of FT4 between Child A, B, and C, the lowest levels found were in the Child C group (0.7 ± 0.4), followed by the Child B group (1.3 ± 0.9), while the Child A group was within the normal range (1.1 ± 0.4). However, in the Child B group (1.3 ± 0.9), FT4 was low in four patients and high in three patients. This could be explained by [
The present results are in agreement with [
The present results disagree with [
When comparing the mean serum levels of TSH in Child A, B, and C, it was found to be the highest in the Child C group (18.1 ± 14.3), followed by the Child B group (3.3 ± 3.1), while the Child A group was within the normal range (1.5 ± 1.2).
This is in agreement with [
However, it disagrees with [
Mohamed Abdel-FattahEl-Feki,Nilly HelmyAbdalla,Mohamed IbrahimAtta,Ahmed AminIbrahim, (2016) Serum Level of Thyroid Hormones in Patients with Chronic Hepatitis C Virus Infection. Open Journal of Endocrine and Metabolic Diseases,06,126-134. doi: 10.4236/ojemd.2016.63017