األستاذ الدكتورفريال صالح القال

الحارة المناطق طب أستاذوالحميات

الطـب طنطا - كليـة جامعة

األستاذ الدكتور حامد سليمانحنان

الحارة أستاذ المناطق طبوالحميات

طنطا – جامعة الطـب كليـة

المشرالمشر فونفون

Prof. Dr Ferial Salah El-Din El-Kalla

Professor of Tropical Medicine & Infectious diseasesFaculty of Medicine

Tanta University 

Prof. Dr Hanan Hamed Soliman Professor of Tropical Medicine &

Infectious diseasesFaculty of Medicine

Tanta University 

• Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting, it manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma.(Vilstrup H et al. , 2014).

Although the precise pathophysiologic mechanisms are not completely understood, current available evidence suggests that the accumulation of neurotoxins, regularly disposed by liver function, is the primary cause of this condition, predisposing to neuro-transmission changes (Ahboucha, 2011).

Hepatic encephalopathy is

reversible with treatment. This relies on

suppressing the production of the toxic

substances in the intestine and is most

commonly done with the laxative

lactulose or with non-absorbable

antibiotics. In addition, the treatment of

any underlying condition may improve

the symptoms (Cash WJ et al., 2010).

Manganese is a structural part of

arginase, an important enzyme in the

urea metabolism.

Manganese also acts as a cofactor of

numerous enzymes in the Krebs cycle,

particularly in the decarboxylation

process.

Magnetic Resonance Imaging (MRI)

studies suggest the accumulation of

Manganese and the development of

osmotic abnormalities in the brains of

patients with cirrhosis

In patients with hepatic encephalopathy increased blood levels of Manganese, a well-known neurotoxic metal, with biliary excretion has been described. Furthermore, the metal is found accumulated in basal ganglia of cirrhotic and liver failure patients (Mas, 2006).

In addition, multiple studies

reported that a correlation exists

between serum Manganese levels,

activities of liver enzymes, brain MRI

abnormalities and signs of

Parkinsonism in patients with

cirrhosis (Lazeyras F et al., 2002).

The aim of this work is to study

Manganese levels in blood of cirrhotic

patients with hepatic encephalopathy

in relation to grading of hepatic

encephalopathy and clinical

prognosis.

The study was conducted on 90 subjects from the

outpatient clinic and inpatient wards of the Tropical

medicine and infectious diseases department, Tanta

University Hospital, they were further subdivided

into:

Group I: 50 cirrhotic patients with hepatic

encephalopathy.

Group II: 30 cirrhotic patients without hepatic

encephalopathy.

Group III: 10 healthy subjects as a control group.

All patient and control groups were

subjected to the following:

Detailed history taking and physical examination.

Routine Laboratory investigations including :

Complete blood picture, Serum creatinine, Blood glucose level. Liver function tests: total serum bilirubin, serum AST, serum ALT, serum albumin and prothrombin activity.

All patients were classified and scored according to modified Child-Pugh criteria.

Serum Manganese (Mn) concentration measurement.

Ultrasound examination of the abdomen. For the liver, spleen, portal vein diameter, and presence of ascites.

Follow up of HE patients for a 6 month period.

This study was carried out on 3 groups Group I: included 50 cirrhotic patients presenting with hepatic encephalopathy.

Group II: included 30 cirrhotic patients with no history of hepatic encephalopathy.

Group III: included 10 healthy control subjects of matched age, sex, and educational level with the patient groups.

The results of the study were tabulated and statistically analyzed in tables and figures as following

VARIABLE Group I Group II Group III P value

Haemoglobi

n

10.39 ± 0.54

11.35 ± 0.63

14.67 ± 0.92

<0.001*

Platelet count

132.26 ± 27.33

167.65 ± 45.99

244.15 ± 91.15

<0.001*

RBC count 3.30 ± 0.23 3.52 ± 0.47 4.94 ± 0.31 <0.001*

WBCs count 2.63 ± 1.08 3.41 ± 0.75 4.19 ± 0.65 <0.001*

COMPARISON BETWEEN GROUPS IN RELATION TO CBC

VARIABLE Group I Group II Group III P value

Serum albumin

2.07 ± 0.45 2.96 ± 0.81 4.49 ± 0.36 <0.001*

Total serum bilirubin

8.97 ± 8.56 1.54 ± 0.88 0.49 ± 0.23 <0.001*

ALT levels 63.50 ± 37.80

42.70 ± 10.59

23.26 ± 4.47

<0.001*

AST levels 130.84 ± 67.58

64.60 ± 17.80

36.07 ± 2.72

<0.001*

Creatinine 1.87 ± 1.00 1.65 ± 1.37 0.87 ± 0.15 0.034*

COMPARISON BETWEEN GROUPS IN RELATION TO LIVER AND KIDNEY FUNCTIONS:

Serum Mn level

87.38 ± 4.96

62.44 ± 8.48

15.90 ± 1.05

<0.001*

Positive history of GIT bleeding

58 % 20 % - <0.001*

Modified Child-Pugh Score

12.48 ± 0.97

7.87 ± 1.07

-

<0.001*

VARIABLE Group I Group II Group III P value

Correlation between serum Mn levels and other parameters

Parameter R PTotal Serum Bilirubin 0.315 0.026*

Direct Bilirubin0.265 0.015*

Serum albumin-0.363 0.010*

INR0.686 < 0.001*

Child Score0.987 < 0.001*

Grade of ascites0.149 0.020*

Presence of ascites0.178 <0.001*

HE grade0.165 0.012*

Recurrence0.002 < 0.001*

There was a positive significant correlation between serum Mn levels and total bilirubin levels.

There was a negative significant correlation between serum Mn levels and serum albumin.

P = 0.010

P = 0.001

There was a positive significant correlation between serum Mn levels and INR.

P = 0.001

There was a positive significant correlation between serum Mn levels and PT.

P = 0.001

There was a positive significant correlation between serum Mn levels and Child Score.

There was a positive significant correlation between serum Mn levels and grades of HE.

P = 0.012

P < 0.001

There was a positive significant correlation between serum Mn levels and number of recurrences.

From this study we can conclude that:

Cirrhotic patients have high serum

Manganese levels.

Elevated serum Manganese levels correlate to

modified Child-Pugh score, total bilirubin,

direct bilirubin, serum albumin, presence of

ascites, grades of HE and INR.

Cirrhotic patients with advanced modified

Child-Pugh class are more prone to have

hepatic encephalopathy and have higher serum

Manganese levels.

Cirrhotic patients with hepatic encephalopathy have higher serum Manganese levels than those without hepatic encephalopathy indicating that such elevated serum Manganese levels may play an important role in the pathogenesis of hepatic encephalopathy.

There was a significant difference between serum Mn levels in different grades of hepatic encephalopathy.

There was a statistically significant difference in serum Mn levels between patients with different numbers of HE recurrence during a 6 month follow up period with a positive correlation between serum Mn levels and number of recurrences.

Serum Mn levels can be used as a predictor of clinical prognosis.

There was no significant difference in serum Mn levels between HE patients that died or survived during a 6 month follow up period.

Blood Mn can’t be considered as a potential prognostic factor for death in patients with hepatic encephalopathy.

We recommend serum

Manganese level measurement to be added

to routine investigations of cirrhotic patients

liable for HE.

Further studies on a large number of

patients are recommended to investigate the

therapeutic effect of decreasing the elevated

serum Manganese level on onset and

progression of hepatic encephalopathy in

cirrhotic patients .