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ORIGINAL ARTICLE
Year : 2015  |  Volume : 12  |  Issue : 3  |  Page : 87-92

Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients due to chronic hepatitis C


Department of Internal Medicine, Gastroenteology and Hepatology Unit, Tanta University Hospital, Tanta, Egypt

Date of Web Publication16-Oct-2015

Correspondence Address:
Mohamed Abd El-Raouf Tawfik
Department of Internal Medicine, Gastroenteology and Hepatology Unit, Tanta University Hospital, Tanta
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.157935

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  Abstract 

Background and Aim: Liver and thyroid hormones are powerfully correlated so thyroid hormone abnormalities are seen in patients of liver diseases We evaluated serum thyroid hormone levels in chronic hepatitis C cirrhotic patients with and without hepatic encephalopathy. Patients and Methods: Our study was carried out on one hundred patients with chronic hepatitis C (CHC) related liver cirrhosis (66 male and 34 female). they were divided to three groups: Group I which included 40 patients proved to have liver cirrhosis due to CHC with hepatic encephalopathy (26 male and 14 female), Group II which included 60 patients proved to have liver cirrhosis due to CHC without hepatic encephalopathy (40 males and 20 females), Group III which included 20 healthy subjects was taken as control group (12 males and 8 females). Free tri-iodothyroinine (FT3), free thyroxine (FT4), total T3, total T4 and thyrotropine stimulating hormone (TSH) were tested. Results: (Group I) and (Group II) showed a significant decrease in T3 and FT3 levels compared to controls (Group III) whereas there was no difference in serum T4, TSH and FT4 levels. all (Group I) had significantly reduced levels of T3 and FT3 compared to (Group II), whereas there was no difference in T4, FT4 and TSH levels. Conclusion: Patients with chronic CHC have significant lower serum FT3 and T3. Patients with hepatic encephalopathy were found to have exceedingly low serum T3 and FT3 levels. Depressed serum T3 and FT3 levels, together with a prolonged prothrombin time and hypo-albuminemia, therefore appear to be characteristic of decompensated cirrhotic patients prone to develop hepatic encephalopathy.

Keywords: Cirrhosis, hepatic encephalopathy, thyroid function tests


How to cite this article:
El-Sawy AA, Tawfik MA. Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients due to chronic hepatitis C. Thyroid Res Pract 2015;12:87-92

How to cite this URL:
El-Sawy AA, Tawfik MA. Low serum free and total tri-iodothyronine hormones as possible prognostic factors in liver cirrhotic patients due to chronic hepatitis C. Thyroid Res Pract [serial online] 2015 [cited 2020 Sep 21];12:87-92. Available from: http://www.thetrp.net/text.asp?2015/12/3/87/157935


  Introduction Top


Liver cirrhosis is a slowly progressing disease in which healthy liver tissue is replaced with scar tissue. It is the end result of the fibrogenesis that occurs with chronic liver injury. The destruction of hepatic normal architecture and loss of liver cells prevent the liver from functioning normally. [1]

Liver cirrhosis may results from multi-factorial liver diseases mainly chronic hepatitis C virus (HCV), chronic hepatitis B virus (HBV), alcohol, drug induced, hemochromatosis, Wilson disease, non alcohol fatty liver disease (NAFLD) and Alpha-1-antitrypsin deficiency. [1]

In western countries the prevalence of alcoholic cirrhosis, non alcohol fatty liver disease (NAFLD), and autoimmune liver diseases are increasing, while in developing countries hepatitis viruses B and C are the predominant risk factors for liver cirrhosis. [2] In Egypt, the prevalence of HCV infection among general population has been estimated to be around 14%. [3],[4]

Liver cirrhosis may be compensated or decompensated. Decompensated cirrhosis may be manifested by jaundice, ascites, hepatic encephalopathy, bleeding varices, hepatorenal syndrome, hyponatraemia and spontaneous bacterial peritonitis. [5]

Liver and thyroid hormones are powerfully correlated so thyroid hormone abnormalities are seen in patients of liver diseases, although they are clinically euthyroid. [6] The liver plays an important role in thyroid hormones metabolism, being involved in their conjugation, excretion and peripheral de-iodination, and in synthesizing thyroid binding globulin (TBG). [7],[8] The association between chronic liver diseases and thyroid dysfunctions has often been reported, but the association between thyroid dysfunctions and decompensated liver cirrhosis with hepatic encephalopathy has limited available reported information. The available reported studies have revealed that thyroxine (T4) levels are usually within normal limits, but, as cirrhosis progresses, free T4 (FT4) levels increase secondary to decreased serum levels of T4 binding protein [9] and at the same time other studies reported that triiodothyronine (T3) and free T3 (FT3) concentrations are usually decreased in correlation with the severity of liver cirrhosis, but this is still controverted. [10]

To our knowledge, there have been limited studies comparing thyroid dysfunctions in patients with decompensated cirrhosis and those with cirrhosis complicated with hepatic encephalopathy.

In this study we will investigate thyroid hormone levels in chronic hepatitis C related cirrhotic patients with and without hepatic encephalopathy. At the same time we will attempt to determine whether or not thyroid function tests may be a useful prognostic indicator for the development of hepatic encephalopathy in decompensated cirrhotic patients.


  Patients and Methods Top


Our study was carried out on hundred patients with chronic hepatitis C related liver cirrhosis (66 male and 34 female, mean age 54.5 ± 17.5 years, range 37-72 years); they were consecutively admitted to hepatology unit of internal medicine department at Tanta university hospitals.

An informed consent was taken from all participants. All the records were confidential. The results of this research will be used only in scientific purpose. Any unexpected risks appeared during the course of the research were be cleared to participants and the clinical committee on time.

The studied patients and the control subjects were divided to the three groups

Group I which included 40 patients proved to have liver cirrhosis due to chronic hepatitis C with hepatic encephalopathy (26 male and 14 female, mean age 59.5 ± 12.5 years, range 47-72 years), this group will be divided to two subgroups: Subgroup Ia which included 20 cirrhotic patients having hepatic encephalopathy and still survive (survivors) (mean age 59.5 ± 12.5 years, range 47-72 years), and subgroup Ib which included 20 cirrhotic patients having hepatic encephalopathy but died during the course of treatment (non-survivors) (mean age 60 ± 7 years, range 53-67 years).

Group II which included 60 patients proved to have liver cirrhosis due to chronic hepatitis C without hepatic encephalopathy (40 males and 20 females, mean age 47.5 ± 10.5 years, range 37-58 years); this group was divided to three subgroups according to Child's Pugh classification: Subgroup IIa that included 20 patients with Child's Pugh class A (mean age 56.5 ± 9.5 years, range 37-56 years), subgroup IIb which 20 patients with Child's Pugh class B (mean age 50.5 ± 7.5 years, range 43-58 years), and subgroup IIc which included 20 patients with Child's Pugh class C (mean age 49.5 ± 8.5 years, range 41-58 years).

Group III which included 20 healthy subjects was taken as control group (12 males and 8 females, mean age 51.5 ± 15.5 years, range 36-67 years).

All studied patients will be proved to have chronic hepatitis C related liver cirrhosis. Exclusion Criteria of our study were as following: Liver cirrhosis with negative HCV PCR, abnormal findings on clinical thyroid examination, a present or past history of thyroid disease, taking any drug known to affect thyroid function including recent or past history of interferon therapy, abnormal findings in thyroid ultarsaound and finally patients with antithyroid AB positive.

The diagnosis of cirrhosis related hepatitis C was based on: Full case history, full clinical examination, liver biochemical profile, ultra-sound findings, liver fibroscan or liver biopsy (if possible), anti HCV antibodies.

The functional severity of the liver injury was determined on the basis of the Child-Pugh grading system.

Thyroid hormones dysfunctions: In all cases, blood samples for hormone determinations were drawn in the morning after overnight fasting for measurement of FT3, FT4, total T3, total T4 and thyrotropine stimulating hormone (TSH).

Statistical analysis

All patients' data were tabulated and processed using SPSS 10.0 (Statistical package for science and society). Student's t test was used to compare the continued variables between two groups. The analysis of variance (ANOVA) was used to test the significance of continued variables within groups. All values are reported as mean ± standard deviation. In all tests P value was considered significant if < 0.05.


  Results Top


As illustrated in [Table 1] and [Figure 1] and [Figure 2] our studied patients with hepatic encephalopathy (group I) and all cirrhotic patients (group II) showed a significant decrease in T3 and FT3 levels compared to controls (group III) (63.55 ± 15.66 ng/dl vs 95.55 ± 25.72 and 70.44 ± 21.76 vs 95.55 ± 25.72 with P < 0.0001 for T3 and 1.023 ± 0.2005 pg/ml vs 3.061 ± 0.5245 and 2.151 ± 0.6698 vs 3.061 ± 0.5245 with P < 0.0001 for FT3 respectively), whereas there was no difference in serum T4, TSH and FT4 levels.
Figure 1: Comparison between both all cirrhotic patients and all hepatic encephalopathy patients with control subjects as regards total T3


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Figure 2: Comparison between both all cirrhotic patients and all hepatic encephalopathy patients with control subjects as regards (FT3, FT4, T4 and TSH)


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Table 1: Comparison between both all cirrhotic patients and all hepatic encephalopathy patients with control subjects as regards thyroid functions


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At the same time, as illustrated in [Table 2] we found that all cirrhotic patients with hepatic encephalopathy (Group I) had significantly reduced levels of T3 and FT3 compared to all cirrhotic patients without hepatic encephalopathy (group II) (P = 0.0392 for T3 and <0.0001 for FT3) whereas there was no difference in T4, FT4 and TSH levels.
Table 2: Comparison between all cirrhotic patients and hepatic encephalopathy patients as regards thyroid functions


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Decompensated Child C cirrhotic patients had significantly lower serum T3 and FT3 levels than Child A and Child B groups (P < 0.0001). No significant differences were observed when serum T4, FT4 and TSH levels were compared among Child A, Child B and Child C groups as illustrated in [Table 3].
Table 3: Comparison between all cirrhotic patients as regards thyroid functions and Child's classification


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Our results as illustrated in [Table 4] showed that no significant differences in T3, T4, TSH, FT3and FT4 levels were observed between survivors (Group Ia) and non-survivors (Group Ib) with hepatic encephalopathy.
Table 4: Comparison between survivor and non survivor hepatic encephalopathy patients as regards thyroid functions


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At the same time both survivors (Group Ia) and non-survivors (Group Ib) with hepatic encephalopathy patients had significantly decreased T3 and FT3 where there was no significant difference as regard T4, FT4 and TSH levels as illustrated in [Table 5] and [Figure 3] and [Figure 4].
Figure 3: Comparison between survivor and non survivor hepatic encephalopathy patients as regards total T3


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Figure 4: Comparison between survivor and non survivor hepatic encephalopathy patients as regards (FT3, T4, FT4 and TSH)


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Table 5: Comparison between survivor and non survivor hepatic encephalopathy patients with Child's C patients as regards thyroid functions


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  Discussion Top


The liver plays an important role in thyroid hormones metabolism, being involved in their conjugation, excretion and peripheral de-iodination, and in synthesizing thyroid binding globulin (TBG). [7],[8]

The association between chronic liver diseases and thyroid dysfunctions has often been reported, but the association between thyroid dysfunctions and decompensated liver cirrhosis with hepatic encephalopathy has limited available reported information. The available reported studies have revealed that T4 levels are usually within normal limits, but, as cirrhosis progresses, FT4 levels increase secondary to decreased serum levels of T4 binding protein [9] and at the same time other studies reported that T3 and FT3 concentrations are usually decreased in correlation with the severity of liver cirrhosis, but this is still controverted. [10]

Thyroid dysfunction has been reported previously in a variety of non-thyroid illnesses including liver, pulmonary and renal neoplastic disease, severe systemic illness, fasting, malnutrition, postoperative state, physical trauma and acute infections. Low total and fT3 with normal total T4 and thy-rotropin concentrations in the absence of clinical hypothyroidism have been frequently reported in patients with non-thyroidal illnesses. [11],[12],[13] Several researches has been performed to assess the relationship between liver disease and thyroid hormones. [7],[8],[11],[14]

The results of our study showing that the studied patients with hepatic encephalopathy (group I) and all cirrhotic patients (Group II) showed a significant decrease in T3 and FT3 levels compared to controls (Group III) with P < 0.0001 for T3 and FT3, whereas there was no difference in serum T4, TSH and FT4 levels.

These results are matching with Hepner and Walfish who reported a significant inverse correlation between serum T3 concentrations and the severity of liver dysfunction. A progressive decrease in T3 levels in chronic liver diseases has been described as indicative of a poor prognosis. [14],[15],[16]

Authors ascribed this finding to diminished conversion of T4 to T3 and impaired metabolism of thyroxine binding proteins. [14],[15],[16]

In the present study we demonstrated significant decrease in both FT3 and T3 levels parallel to the severity of liver dysfunction according to Child's classification where patients with Child's C illustrated significant decreased FT3 and T3 levels than Child's A and Child's B. These results are similar to many researchers [17],[18],[19] who demonstrated a fall in FT3and T3 parallel to severity of the disease, and a good correlation between T3 concentrations, serum albumin and prothrombin time. These results suggest that serum T3 and FT3 concentrations may be considered a sensitive index of hepatic function in liver disease. These results are matching also with Kayacetin et al., [19] who compared cirrhotic patients with normal subjects and chronic hepatitis patients. They suggested that T3 serum levels inversely paralleled severity of liver dysfunction. [8]

Our study compared between cirrhotic patients with and without hepatic encephalopathy and demonstrated similar findings to that demonstrated by Kayacetin et al., [19] who determined the alterations of thyroid hormone level in non-alcoholic decompensated cirrhotic patients with and without hepatic encephalopathy and found a significant reduction in serum FT3 in non-alcoholic cirrhotic patients compared with a control group, the lowest values being found in patients with hepatic encephalopathy. Low FT3 levels may be due to reduced extra-thyroidal T4-to-T3 conversion, the mechanism being inversely related to the degree of hepatic dysfunction.

At the same time aur results are similar to that found by Kayacetin et al., [19] as we found no significant difference in functional thyroid parameters between patients surviving and not surviving hepatic encephalopathy. These findings are in contrary to Guven et al., who reported lower T3 levels in patients who died than in patients who survived. [17] The reason for this difference is not clear.

In conclusion, patients with chronic hepatitis C cirrhosis have significant lower serum FT3 and T3 than non-cirrhotics. At the same time patients with decompensated liver disease complicated by hepatic encephalopathy subsequent to chronic hepatitis C cirrhosis were found to have exceedingly low serum T3 and FT3 levels. Depressed serum T3 and FT3 levels, together with a prolonged prothrombin time and hypo-albuminemia, therefore appear to be characteristic of decompensated cirrhotic patients prone to develop hepatic encephalopathy.

 
  References Top

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Scheuer PJ, Lefkowitch JH. Cirrhosis. Liver biopsy Interpretation. 7 th ed. Philadelphia: Elsevier Saunders; 2006. p. 171-190.  Back to cited text no. 1
    
2.
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3.
El-Zayadi A, Abaza H, Shawky S, Mohamed MK, Selim OE, Badran HM. Prevalence and epidemiological features of hepatocellular carcinoma in Egypt-a single center experience. Hepatol Res 2001;19:170-9.  Back to cited text no. 3
    
4.
Esmat G. Hepatocellular carcinoma: The magnitude of the problem in Egypt, 6 th international conference of oncology, surgery and gastroenterology. Towards a Healthy Liver in Egypt. April, 10-12:54.  Back to cited text no. 4
    
5.
Kim WR, Biggins SW, Kremers WK, Wiesner RH, Kamath PS, Benson JT, et al. Hyponatremia and mortality among patients on liver transplant waiting list. N Engl J Med 2008;359:1018-26.  Back to cited text no. 5
    
6.
Malik R, Hodgson H. The relationship between the thyroid gland and the liver. QJM 2002;95:559-69.  Back to cited text no. 6
    
7.
Babb RR. Associations between diseases of the thyroid and the liver. Am J Gastroenterol 1984;79:421-3.  Back to cited text no. 7
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8.
Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: Evidence for multiple abnormalities despite clinical euthyroidism. Gut 1983;24:631-6.  Back to cited text no. 8
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Bianchi GP, Zoli M, Marchesini G, Volta U, Vecchi F, Iervese T, et al. Thyroid gland size and function in patients with cir-rhosis of the liver. Liver 1991;11:71-7.  Back to cited text no. 9
    
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Sheridan P. Thyroid hormones and the liver. J Clin Gastroenterol 1983;12:797-818.  Back to cited text no. 10
    
11.
Chopra IJ, Soloman DH, Hepner GW, Morgenstein AA. Misleadingly low free thyroxine index and usefulness of reverse triiodothyronine measurement in non thyroidal illnesses. Ann Intern Med 1979;90:905-12.  Back to cited text no. 11
    
12.
Kaptein EM, Weiner JM, Robinson WJ, Wheeler WS, Nicoloff JT. Relationship of altered thyroid hormone indices to survival in nonthyroidal illnesses. Clin Endocrinol 1982;16:565-74.  Back to cited text no. 12
    
13.
Bermudez F, Surks MI, Oppenheimer JH. High incidence of de-creased seruμm triidothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab 1975;41:27-40.  Back to cited text no. 13
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14.
Hepner GW, Chopra IJ. Serum thyroid hormone levels in pa-tients with liver disease. Arch Intern Med 1979;139:1117-20.  Back to cited text no. 14
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Walfish PG, Orrego H, Israel Y, Blake J, Kalant H. Serum tri-iodothyronine and other clinical and laboratory indices of alcoholic liver disease. Ann Intern Med 1979;91:13-6.  Back to cited text no. 15
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Klachko DM, Johnson ER. The liver and circulating thyroid hormones. J Clin Gastroenterol 1983;5:465-71.  Back to cited text no. 16
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17.
Guven K, Kelestimur F, Yucesoy M. Thyroid function tests in non-alcoholic cirrhotic patients with hepatic encephalopathy. Eur J Med 1993;2:83-5.  Back to cited text no. 17
    
18.
Thobe N, Pilger P, Jones MP. Primary hypothyroidism masquerading as hepatic encephalopathy: Case report and review of the literature. Postgrad Med J 2000;76:424-6.  Back to cited text no. 18
    
19.
Kayacetin E, Kisakol G, Kaya A. Low serum total thyroxine and free T3 in patients with hepatic encephalopathy due to non-alcoholic cirrhosis. Swiss Med Wkly 2003;133:210-3.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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[Pubmed] | [DOI]



 

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