Pakistan Journal of Medical Sciences

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ISSN 1681-715X

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ORIGINAL ARTICLE

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Volume 25

October - December 2009 (Part-II)

Number  6


 

Abstract
PDF of this Article

Serum zinc level in patients
with liver cirrhosis

Aftab Ahmed Soomro1, Bikha Ram Devrajani2, Khalid Shaikh3,
Syed Zulfiquar Ali Shah4, Tarachand Devrajani5, Ishrat Bibi6

ABSTRACT

Objective: To determine the serum zinc level in patients with liver cirrhosis.

Methodology: This descriptive cross sectional study was conducted at Liaquat University Hospital Hyderabad Sindh, Pakistan. All patients above 12 years of age, of either gender and known (diagnosed) cases of liver cirrhosis were further evaluated for their serum zinc level. The data was analyzed in statistical software (SPSS) and the p value <0.05 was considered as statistically significant.

Result: One hundred twenty seven cirrhotic patients with means age 42.7559 ± 15.8894 were evaluated and assessed. The serum zinc was low in 69% patients. According to Child-Pugh classification 72% zinc deficient cirrhotic subjects were in class C, 16% in class B & 12% in class A. 94% subjects had hepatitis C virus infection, 4% had hepatitis B virus infection and 2% had history of alcoholism.

Conclusion: The serum zinc level was low in patients with liver cirrhosis.

KEY WORDS: Liver cirrhosis, Zinc, Trace elements.

Pak J Med Sci    October - December 2009 (Part-II)    Vol. 25 No. 6    986-991

How to cite this article:

Soomro AA, Devrajani BR, Shaikh K, Shah SZA, Devrajani T, Bibi I.Serum zinc level in patients with liver cirrhosis. Pak J Med Sci 2009;25(6):986-991.


1. Dr. Aftab Ahmed Soomro MD
Consultant Physician,
Department of Medicine,
2. Dr. Bikha Ram Devrajani FCPS
Associate Professor,
Department of Medicine,
3. Dr. Khalid Shaikh MD
Assistant Professor
Department of Medicine
4. Dr. Syed Zulfiquar Ali Shah
PG-Student (FCPS)
Department of Medicine
5. Dr. Tarachand Devrajani
PG-Student (FCPS)
Department of Medicine
6. Dr. Ishrat Bibi
PG-Student (D-Derm)
Department of Dermatology
1-6: Liaquat University of Medical and
Health Sciences (LUMHS),
Jamshoro,
Hyderabad - Pakistan.

Correspondence:

Dr. Syed Zulfiquar Ali Shah
Department of Medicine,
Liaquat University of Medical & Health Sciences
Jamshoro, Hyderabad - Sindh, Pakistan.
Email: zulfikar229@hotmail.com

* Received for Publication: May 15, 2009

* Revision Received: September 9, 2009

* Revision Accepted: September 29, 2009


INTRODUCTION

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar leading to progressive loss of liver function. It is most commonly caused by alcoholism and hepatitis B or C but has many other possible causes.1Epidemiology of liver cirrhosis varies between gender, ethnic groups and geographical distribution. In 2000 liver cirrhosis was the fifth leading cause of death in Mexico2 where as it was 12th most common cause of death in the United States.3

Majority of patients remain symptom free until the advance stage called decomepnsated cirrhosis, characterized by ascites, spontaneous bacterial peritonitis, hepatic coma or variceal bleeding from portal hypertension. The physical examination of patients with cirrhosis may reveal variety of findings that necessitate a hepatic or a gastrointestinal based work-up to determine the aetiology. There is correlation observed between persistently disturbed liver function tests and biopsy-proven underlying hepatic disease so to diagnose the cirrhosis liver biopsy should be considered when all initial and specific measures have failed to confirm.4The treatment strategy is usually against the underlying complication i.e. bleeding esophageal varices managed by endoscopic sclerotherapy or rubber band ligation. Ascites and edema are often responsive to low sodium, diuretic therapy and peritoneal paracentesis.5A low protein diet and agents such as lactulose are used to manage hepatic encephalopathy. Infections such as spontaneous bacterial peritonitis must be aggressively rapidly treated with appropriate antibiotics. Coagulation disorders will sometimes respond to vitamin K and fresh frozen plasma. However liver transplantation is highly effective for the treatment of end-stage cirrhosis.6

The Zinc (Zn, also called spelter) is a metallic element, symbol Zn, atomic number 30 and it is a transition metal in group 12 of the periodic table.7The Recommended Dietary Allowance (RDA) is 8 mg/day for women and 11 mg/day for men. Red meats, especially beef, lamb and liver have some of the highest concentrations of zinc in food.8Nearly two billion people in the developing world are deficient in zinc.9The low serum zinc level is common in patient with liver cirrhosis due to decreased intake, decrease absorption, decreased bioavailability, and increased losses (because of malabsorption). There is also reduced liver protein synthesis in patients with liver cirrhosis, the metallothionein (MT) is an important zinc-binding protein (formed by liver) and is involved in zinc metabolism, homeostasis and its release in number of oxidants, the released zinc will inhibit the activity of the enzymes involved in fibrogenesis (fibrosis) in the liver, all these are yet known pathophysiological mechanisms.10-11Zinc is also essential for some of the neutrophil functions and it appears that zinc has a role in the maintenance of human immunity. Recent evidence suggests that thymic-dependent lymphocytes (T cells are zinc dependent. T-helper and suppressor cells, T-effector cells and T-natural killer cells appear to be zinc dependent.12In a study of Stamoulis et al published by Digestive Diseases and Sciences in 2007 the prevalence of low serum zinc level in cirrhotic patients was 65.3%.13

Therefore keeping all such important points and views in mind the present study was conducted in medical department of Liaquat university hospital - a tertiary care 1500 bedded teaching hospital located in the center of Hyderabad city of province Sindh, Pakistan. The hospital covers both the urban and rural population of province and provides all necessary emergency facilities to the patient. The focus and aim of this study was to evaluate and assess the serum zinc level in patients with liver cirrhosis. So far no study has been conducted on this topic in Pakistan. As such this study will fill the gap, open new forum of discussion and will provide knowledge and information regarding the medical workup of patients with liver cirrhosis. Moreover such parameters and protocol will add some weight in the management of cirrhotic patients.

METHODOLOGY

This descriptive cross sectional study was conducted in the department of Medicine at Liaquat University Hospital (a tertiary care teaching hospital) Hyderabad from August 2008 to January 2009. All patients above 12 years of age, of either gender and were known cases (already diagnosed) of liver cirrhosis who came through outdoor patient department (OPD) for follow up visit were evaluated and enrolled in the study. However the diagnostic parameters and tools of liver cirrhosis were also kept in mind i.e. on the basis of clinical (reduced liver span <8 cm on clinical exam with ascites and splenomegaly), biochemical (prolonged prothrombin time >12 seconds and reduced level of serum albumin <3.5 g/dl), radiological (increased liver echopattern, shrunken liver <8cm in mid-clavicular line, portal vein diameter >1.3 cm and spleen size >13 cm longitudinally) and prior biopsy (presence of widespread fibrosis, obliteration of central vein and regenerating nodules).The detailed history of all such patients was taken and complete physical and relevant clinical examination was performed.

The sample size was calculated by assessing the prevalence of low serum zinc level in liver cirrhosis (65.3%) with 5% margin of error.13The severity of liver cirrhosis was assessed by Child–Pugh score14and viral hepatitis B and C infection was detected by Enzyme-linked immunosorbent assay (ELISA) method. All patients were then advised for fasting serum zinc level whereas the cirrhotic patients who were not vitally stable were admitted and then their serum zinc level was assessed by taking 2cc venous blood sample on next morning. The normal range of serum zinc level is 11-19 mmol/L and the value < 11 mmol/L was considered as low.15The informed consent was taken from every patient or from attendant of patients after full explanation of procedure regarding the study, and all such maneuvers was performed under medical ethics and through the cooperation of whole research team. The serum zinc status was reviewed by panel of expert consultant physicians of the ward and labeled as "low" when the serum level was below the normal range.15

The exclusion criteria of the study were; (a)The patients who were already on zinc therapy. (b) The non-cooperative patients or who refused to give consequent or did not have interest to participate in the study. (c) The patients who were known cases of any autoimmune disease, immunodeficiency disorder (CD4+ count < 200, granulocytopenia < 500/mm3) or already on cancer chemotherapy. (d) The patients already on hormonal therapy. (e) Patients with acute or chronic diarrhea. (f) The patients with history of pregnancy. Regarding ethical justification all the expenses of this study was paid by cooperation of whole research team.

The data were evaluated in statistical program SPSS version 16.0. The variable of serum zinc deficiency was recoded from numeric to categorical i.e. normal and low level. Qualitative data (frequency and percentage) like gender and serum zinc level presented as n (%) and Fisher’s exact (2x2) test of X2 was applied to compare the proportions. The mean + standard deviation (SD) was calculated among the numerical variables and student t-test was applied to compare the means (2 tailed) among the gender and serum zinc level. All the data was calculated on 95% confidence interval. The P value <0.05 was considered as statistically significant level for all the comparisons.

RESULTS

One hundred twenty seven (127) cirrhotic patients were evaluated and assessed with mean age 42.7559 ± 15.8894 (SD). In 107(84%) patients serum zinc level was observed through follow up visit while 20 (16%) patients were not vitally stable so they were hospitalized and assessed for their serum zinc status. The serum zinc level was low in 88 (69%) patients while remaining 39(31%) patients had normal serum zinc level. The gender distribution in relation to serum zinc status, mean and standard deviation of serum zinc level in all cirrhotic patients and in relation to gender is given in Table I-III.

According to Child-Pugh score system 92(72%) zinc deficient subjects were in class C, 20 (16%) were in class B and 15 (12%) were in class A. The 119 (94%) patients had history and evidence for hepatitis C virus infection, 05(4%) had hepatitis B virus infection while 03 (2%) had history of alcoholism. However; fulminant liver failure with low serum zinc level was observed in one patient. The majority of subjects belonged to the periphery of the province Sindh, Pakistan i.e. rural population 104 (82%), whereas remaining 23(18%) was urban population.

DISCUSSION

The liver plays an important role in Zn homeostasis and different Zn compartments have been recognized to explain Zn kinetics in humans; the liver represents a fast-exchangeable Zn pool with an important role in the metabolism of Zn and other trace elements.16In our study the serum zinc level was low in patient with liver cirrhosis, however such observation resembled with two different studies conducted by Go et al and Sullivan et al.17-18 Where as Kalkan et al also identified zinc deficiency in patients with liver disease in his study published in 2002.19It has long been speculated that Zn has a protective effect against liver fibrosis and Zn intake in cirrhosis are based mostly on observations of reduced Zn levels in cirrhotic patients and on the beneficial effects of Zn supplementation on liver metabolism.20-21

In the present study the 94% subjects had viral hepatitis C induced liver cirrhosis, the viral infection induced cirrhosis causes oxidative stress and secondary cellular damage, Low plasma Zn concentrations contribute to oxidative stress and its replenishment by high doses has been considered mandatory.22It has also been thought that Zn could directly affect Hepatitis C viral (HCV) replication, thus supporting structural and functional stability of certain HCV proteins like NS5A and NS3. In our study three patients had alcohol induced liver cirrhosis and we identified and observed that their serum zinc level was low, where as a study on "Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis" shown similar finding.23Animal model studies have shown that Zn supplementation prevented ethanol-induced liver injury under both acute and chronic exposure conditions. Zn supplementations decreases ethanol-induced hepatic Zn depletion, suppressed the elevated cytochrome P450 2E1 activity, and enhances the activity of enzyme alcohol dehydrogenase which will responsible for the suppression of ethanol-induced oxidative stress. Zn administration also enhanced hepatic glutathione (GSH) and Zn related antioxidant capacity.24

In our study the mean age of cirrhotic patients was 42.75 ± 15.88 however such age distribution resembled with the study of Bhise et al.25 In the present study, majority of zinc deficient cirrhotic patients one belonged to rural population and it is similar to the study of Ma et al on "assessment of intake inadequacy and food sources of zinc of people in China" published in 2007.26 In our study, there was male predominance in relation to zinc disturbance with liver cirrhosis however there were no differences in the concentrations of zinc between male and female patients with liver cirrhosis in the study by Dario et al.27

In this series one patient was in fulminant failure and had low serum zinc level however similar finding was also detected by Chetri et al.28 In fulminant hepatic failure and hepatic encephalopathy, biochemical parameters suggesting liver dysfunction presenting inverse correlation with serum Zn levels. The present study identified 4% had hepatitis B virus induced liver cirrhosis and their zinc level was also low where as Gur et al29 states that serum and hepatic Zn levels were reduced in hepatitis B virus (HBV) infected patients with cirrhosis. The Zn depletion in cirrhosis has been attributed to decreased intestinal Zn absorption, increased urinary loss, malnutrition, hypoalbuminemia, portosystemic shunts, and diminished hepatic Zn extraction. Majority of the published studies have suggested that Zn absorption was reduced in cirrhotic patients. Two mechanisms were proposed for Zn malabsorption in liver cirrhosis (1) damage of the small bowel mucosa (2) impairment of pancreatic exocrine function accompanied by reduced synthesis of ligands such as picolinic acid in the liver.30

It has been suggested that some of the clinical features of liver cirrhosis, such as testicular atrophy, loss of body hair, night blindness, poor wound healing, poor appetite, decreased taste and smell acuity, susceptibility to infections, enhanced sensitivity to drugs, and decreased neurocognitive performances, may be related to conditioned Zn deficiency. In some cases Zn supplementation was beneficial to these patients.31The zinc supplementation also reduces the inflammation and contributes to faster inflammation resolution, therefore further advance, modified and related studies are needed to update the data, knowledge and information regarding medical workup of patients with liver cirrhosis.

CONCLUSION

We have identified the lower level of serum zinc level in patients with liver cirrhosis. Therefore a routine biochemical assessment of zinc status in patients with liver cirrhosis is an important step in the management protocol and to reduce progression of the disease.

ACKNOWLEDGEMENT

We are thankful to Mr. Farooq Ahmed Mangnejo for bio-statistical analysis and word-processing of the manuscript according to the Journal’s instruction.

REFERENCES

1. Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J 2004;24 (5):861–80.

2. Mendez-Sanchez N, Villa AR, Chavez-Tapia NC, Ponciano-Rodriguez G, Almeda Valdes P, Gonzalez D, et al. Trends in liver disease prevalence in Mexico from 2005 to 2050 through mortality data. Ann Hepatol 2005;4:52-5.

3. National Center for Health Statistics. National Vital Statistics Report. Chronic liver disease / cirrhosis. [online] 2009 Mar 06 [cited 2009 April 05]. Available from URL: http://www.cdc.gov/nchs/fastats/liverdis.htm

4. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: Part I. Diagnosis and Evaluation. Am Fam Physician 2006;74:756-62.

5. Figueras J, Jaurrieta E, Valls C, Ramos E, Serrano T, Rafecas A, et al. Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg. 2000;190(5):580-7.

6. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis. New Engl J Med 1996;334(11):693-700.

7. Gordon RB, Bertram M, Graedel TE. Metal stocks and sustainability. PNAS 2006;103(5):1209–14

8. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med 2008;14(5-6):353–7

9. Prasad AS. Zinc deficiency: has been known of for 40 years but ignored by global health organizations. BMJ 2003;22;326(7386):409–10.

10. Maret W. Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 2003;133(5 Suppl. 1):1460S–62S.

11. Lee JY, Kim JH, Palmiter RD, Koh JY. Zinc released from metallothionein-III may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury. Exp Neurol 2003;184(1):337-47.

12. McClain CJ, Antonow DR, Cohen DA, Shedlofsky SI. Zinc metabolism in alcoholic liver disease. Alcohol Clin Exp Res 1986;10(6):582-9.

13. Stamoulis I, Kouraklis G, Theocharis S. Zinc and the Liver: An Active Interaction. Digestive Diseases and Sciences 2007;52(7):1595-1612.

14. Durand F, Valla D. Assessment of the prognosis of cirrhosis: Child–Pugh versus MELD. J Hepatology 2005;42:S100–7.

15. Shameer P, Prasad PV, Kaviarasan PK. Serum zinc level in vitiligo: A case control study. Indian J Dermatol Venereol Leprol 2005;71:206-7.

16. Krebs NE, Hambidge KM. Zinc metabolism and homeostasis: the application of tracer techniques to human zinc physiology. Biometals 2001;14:397–412

17. Echejoh GO, Tanko MN, Manasseh AN, Silas OA, Ogala-Echejoh SE, Mandong BM. Liver Cirrhosis in Jos, North - Central Nigeria. Jos Journal of Medicine 2008;3(1):26-29.

18. Sullivan JF, Blotcky AJ, Jetton MM, Hahn HK, Burgh RE. Serum Levels of Selenium, Calcium, Copper Magnesium, Manganese and Zinc in Various Human Diseases. J Nutr 1979;109:1432-37

19. Kalkan A, Bulut V, Avci S, Celik I, Bingol NK. Trace elements in viral hepatitis. J Trace Elem Med Biol 2002;16:227- 230.

20. Capocaccia L, Merli M, Piat C, Servi R, Zullo A, Riggio O. Zinc and other trace elements in liver cirrhosis. Ital J Gastroenterol 1991;23:386–91.

21. Leveille CR, Arias IM. Pathophysiology and pharmacologic modulation of hepatic fibrosis. J Vet Intern Med 1993;7:73–84.

22. Stehbens WE. Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol 2004;77:121–32.

23. Bode JC, Hanisch P, Henning H, Koenig W, Richter FW, Bode C. Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology 1988;8:1605–9.

24. Polavarapu R, Spitz DR, Sim JE, Follansbee MH, Oberley LW, Rahemtulla A, et al. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology 1998;27:1317-23.

25. Bhise SB, Dias RJ. Monoethylglycinexylidide (MEGX) as a liver function test in cirrhosis. Indian J Gastroenterol 2007;26:167-9.

26. Ma G, Li Y, Jin Y, Du S, Kok FJ, Yang X. Assessment of intake inadequacy and food sources of zinc of people in China. Public Health Nutr 2007;10(8):848-54.

27. Dario R, Milan K, Zeljko R, Kristina B, Mladen P. Serum Concentration of Zinc, Copper, Manganese and Magnesium in Patients with Liver Cirrhosis. Coll Antropol 2006;30(3): 523-28.

28. Chetri K, Choudhuri G. Role of trace elements in hepatic encephalopathy: zinc and manganese. Indian J Gastroenterol 2003;22(2):S28–30.

29. Gur G, Bayraktar Y, Ozer D, Ozdogan M, Kayhan B Determination of hepatic zinc content in chronic liver disease due to hepatitis B virus. Hepatogastroenterology 1998;45:472–76.

30. Ijuin H. Evaluation of pancreatic exocrine function and zinc absorption in alcoholism. Kurume Med J 1998;45:1-5.

31. Grungreiff K. Zinc in liver disease. J Trace Elem Exp Med 2002;15:67-78.


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