Editor in chief

M.Y.Taher

Founder Editors

Hilmy Abaza

Seham Abdel Reheem

Co-Editors

Ahmed Shawky

FathAlla Sidkey

Maher Osman

Mohamed Sharaf De Din

International Advisory Board

JP Galmiche France

A Sandeberg Sweden

X Rogiers Belgium

S Jensen Denmark

Des Verrannes France

Antonio Ascione Italy

S Brauno Italy

P Almasio Italy

National Advisory Board

Mohamed El Gendi

Moustafa El Henawi

Amira Shams Eldin

Nabil Abdel Baki

Hoda E-Aggan

M Essam Moussa

Ahmed Bassioni

Saeid Elkyal

Abdel Fataah Hano

Tarek Thabet

Ahmed Hussein

Khaled Madboli

Ezzat Aly

Contents Alexandria Journal of

Hepatogastroenterology, Volume IIX ( I )

April 2012

------------------------------------------- Manuscript Submission: For information and to

submit manuscripts please contact the editors by

e-mail at : dryousrytaher@yahoo.com

fathallas@yahoo.com

Disclaimer: The Publisher, the Egyptian Society of

Hepatology Gastroenterology and Infectious Diseases

in Alexandria, and Editors cannot be held responsible

for errors or any consequences arising from the use of

information contained in this journal; the views and

opinions expressed do not necessarily reflect the those

of the Publisher, The Egyptian Society of Hepatology

Gastroenterology & Infectious Diseases in Alexandria,

Editors, neither dose the publication of advertisements

constitute any endorsement by the Publisher, society,

and editors of the products advertised.

-------------------------------------------

Editorial:

Gastric Outlet Obstruction (GOO)

M Y Taher*,Wael Nabil**

Alexandria University HPB Unit* and surgical department **

-------------------------------------------

Review Article:

Epidemiology and Current Management of Dyspepsia

MY Taher , H.Abazza

Alexandria University

-------------------------------------------

Review Article:

Restrictive Transfusion Strategy, Improved the Outcomes

Among Patients with Acute Upper Gastrointestinal

Bleeding. (AUGIB)

MY Taher Alexandria University

-------------------------------------------

Case Report:

Permeated Surgical Gauze after Open Cholecystectomy

Presented as Gastric Outlet Obstruction (GOO)

M Y Taher*,Wael Nabil** Alexandria University HPB Unit* and surgical department **

-------------------------------------------

Original Article:

Relation Of Pretreatment Serum B12 Level And Response

To Treatment With Interferon And Ribavirin In Patients

With Chronic HCV Infection

Khaled Mahmoud Mohiedeen and Akram deghedy* Tropical medicine and clinical pathology* department,

alexandria faculty of medicine

-------------------------------------------

Original Article:

Dual Impact of Chronic Hepatitis C and Schitosomal

Hepatic Fibrosis on Gall Bladder Disease

Fathia E Asal1, Ahmed Khalid Tawfik1, Raafat A Salah1 &

Abdelmonem N Darwish2

Tropical Medicine1 and Diagnostic Radiology2 Departments, Faculty of Medicine, Tanta University, Egypt

-------------------------------------------

Editorial

Gastric Outlet Obstruction (GOO)

M Y Taher*,Wael Nabil**

Alexandria University HPB Unit* and surgical department **

ABSTRACT

GOO a clinical condition due to an obstruction at the level of the pyloroduodenal junction. Individuals with gastric

outlet obstruction present with recurrent attacks of vomiting with or without upper abdominal pain .Usually distension

of the upper abdomen is noticed as stomach dilate to accommodate ingested food. Causes of gastric outlet obstruction

include both benign causes Benign causes such as ciacterised peptic ulcer, as well as malignant causes, such as gastric

cancer. Treatment of the condition depends upon the underlying cause; it starts with endoscopic diltation with balloons

or stenting using flexible expandable metallic stents in some sitauations when patients are not candidate for surgery.

The incidence of gastric outlet obstruction is difficult to define exactly . We are in the era of PPIs and endoscopy that

was reflected on the incidence of complications from peptic ulcer disease. PPIs midified the natural course of peptic

ulcer diasease . Benign disease was reported to be main cause in the majority of cases of GOO in adults, while

malignancy accounted for only 10 to 39 percent of cases . By contrast, in recent decades, 50 to 80 percent of cases have

been attributable to malignancy. Updated estimates are not available but the need for surgery is thought to have declined

because of advancements in endoscopic methods to treat GOO such as dilation and stenting.GOO in infancy and

childhood is due to congenital causes i.e antral diaphragm, pyloric atresia, and infantile hypertrophic pyloric

stenosis(IHPS)], or acquired causes including peptic ulcer, caustic ingestion, tumor, chronic granulomatous disease, and

eosinophilic gastroenteritis .IHPS is the frequent cause with an incidence of up to 1.5–3 per 1,000 live births. When

IHPS is excluded, however, the other causes of GOO in children are relatively rarely encountered(1).

Epidemiology

The incidence of gastric outlet obstruction is

not known precisely. It is likely to have

declined in recent years because of the decline

in peptic ulcer disease, which has historically

been an important cause of GOO.

Etiology

The term gastric outlet obstruction is a

misnomer since many cases are not due to

isolated gastric pathology but rather involve

duodenal or extra lumen disease. The

predominant causes have changed substan-

tively with the identification of H. pylori and

the use of proton pump inhibitors.IHPS can

be diagnosed easily and respond well to

Ramstedt's Pyloromyotomy. Other causes of

gastric outlet obstruction are; pyloric atresia,

prepyloric webs, and diaphragm which can be

managed by excision of membrane and

pyloroplasty. The prepyloric stricture of

unknown etiology is very rare in infants, and

it should be kept in mind when IHPS is ruled

out.Gastric outlet obstruction (GOO) is a

classic indication for surgery in complicated

peptic ulcer disease. The acquired cause of

GOO in infants are acid peptic disease,

neoplasm and caustic ingestion' .With an

increase in the incidence of peptic ulceration

in pediatric population, complications like

gastro-duodenal perforation and pre-pyloric

stricture are also encountered Generally, the

course of peptic ulcer in children is longer

than that in adults, so the degree of stricture,

secondary to long-standing peptic ulceration,

in children may be very significant despite the

advances in medical management but it

usually presents in late childhood. So,

medical therapy for children with GOO

secondary to peptic ulcer cannot be expected

to relieve the obstruction component.(1,2,3)

Altho-ugh there are few reports of GOO due

to prolapsing gastric polyp in adults, but no

report of GOO secondary to antral mass

combined with gastric ulcer was found in

pediatric age group. Sometimes inflammatory

polyp might be resulted from H. pylori

infection. Although there are few cases of

peptic ulcer perforation had been reported but

pre-pyloric stricture due to peptic ulcer had

not been reported. The GOO due to healed

peptic ulcer, perforation and malignancy are

seen in adult but rarely seen in pediatric age

group. In peptic ulcer diseases, GOO is usu-

ally caused by a combination of edema,

spasm, fibrotic stenosis and gastric atony.

Chan et al. reported their experience with 32

children with duodenal ulcers. GOO caused

by peptic ulcer diseases can be resolved by

medical treatment, [12] vagotomy, pyloro-

plasty or endoscopic balloon catheter

dilatation. However GOO secondary to

gastric ulcer in infant had not been reported.

As per our knowledge this is the first case

report of prepyloric stricture presented as

GOO(4,5). Gastric outlet obstruction can be a

diagnostic and treatment dilemma. As part of

the initial workup, exclude the possibility of

functional nonmechanical causes of obstr-

uction, such as diabetic gastroparesis. Once a

mechanical obstruction is confirmed,

differentiate between benign and malignant

processes because definitive treatment is

based on recognition of the specific

underlying cause. Delay of diagnosis and

treatment may result in further compromise of

the patient's nutritional status. Delay will also

further compromise edematous tissue and

complicate surgical intervention. The

incidence of gastric outlet obstruction (GOO)

has been reported to be less than 5% in

patients with (PUD) , which is the leading

benign cause of the problem. Five percent to

8% of ulcer-related complications. The

incidence of GOO in patients with

peripancreatic malignancy, the most common

malignant etiology, has been reported as 15-

20%.

Pathophysiology

Intrinsic or extrinsic obstruction of the pyloric

channel or duodenum is the usual

pathophysiology of gastric outlet obstruction;

as previously noted, the mechanism of

obstruction depends upon the underlying

etiology. Patients present with intermittent

symptoms that progress until obstruction is

complete. Vomiting is the cardinal symptom.

Initially, patients may demonstrate better

tolerance to liquids than solid food. In a later

stage, patients may develop significant weight

loss due to poor caloric intake. Malnutrition is

a late sign, but it may be very profound in

patients with concomitant malignancy. In the

acute or chronic phase of obstruction,

continuous vomiting may lead to dehydration

and electrolyte abnormalities. When obstruct-

tion persists, patients may develop significant

and progressive gastric dilatation. The

stomach eventually loses its contractility.

Undigested food accumulates and may

represent a constant risk for aspiration

pneumonia.

Presentation

Nausea and vomiting are the cardinal

symptoms of gastric outlet obstruction.

Vomiting usually is described as nonbilious,

and it characteristically contains undigested

food particles. In the early stages of

obstruction, vomiting may be intermittent and

usually occurs within 1 hour of a meal.

Patients with gastric outlet obstruction

resulting from a duodenal ulcer or incomplete

obstruction typically present with symptoms

of gastric retention, including early satiety,

bloating or epigastric fullness, indigestion,

anorexia, nausea, vomiting, epigastric pain,

and weight loss. They are frequently malno-

urished and dehydrated and have a metabolic

insufficiency. Weight loss is frequent when

the condition approaches chronicity and is

most significant in patients with malignant

disease.Abdominal pain is not frequent and

usually relates to the underlying cause, eg,

PUD, pancreatic cancer.Physical examination

often demonstrates the presence of chronic

dehydration and malnutrition. A dilated

stomach may be appreciated as a tympanitic

mass in the epigastric area and/or left upper

quadrant. Dehydration and electrolyte abnor-

malities can be demonstrated by routine

laboratory examinations. Increases in BUN

and creatinine are late features of dehydration.

Prolonged vomiting causes loss of hydro-

chloric (HCl) acid and produces an increase

of bicarbonate in the plasma to compensate

for the lost chloride and sodium. The result is

a hypokalemic hypochloremic metabolic

alkalosis. Alkalosis shifts the intracellular

potassium to the extracellular compartment,

and the serum positive potassium is increased

factitiously. With continued vomiting, the

renal excretion of potassium increases in

order to preserve sodium. The adrenocortical

response to hypovolemia intensifies the

exchange of potassium for sodium at the

distal tubule, with subsequent aggravation of

the hypokalemia(6). Causes Gastric outlet

obstruction (GOO) is not a single entity; it is

the clinical and pathophysiological conseq-

uence of any disease process that produces a

mechanical impediment to gastric emptying.

Clinical entities that can result in GOO

generally are categorized into 2 well-defined

groups of causes—benign and malignant

.Only37% of patients with GOO have benign

disease and the remaining patients have

obstruction secondary to malignancy. Clinical

entities that can result in GOO generally are

categorized into 2 well-defined groups of

causes-benign and malignant. This classi-

fication facilitates discussion of management

and treatment. In the past, when Peptic Ulcer

disease (PUD)was more prevalent, benign

causes were the most common; however, one

review shows that only 37% of patients with

GOO have benign disease and the remaining

patients have obstruction secondary to

malignancy. The major benign causes of

gastric outlet obstruction (GOO) are PUD,

gastric polyps, ingestion of caustics, pyloric

stenosis , congenital duodenal webs, gallstone

obstruction (Bouveret syndrome), pancreatic

pseudocysts, and bezoars. PUD manifests in

approximately 5% of all patients with GOO.

Ulcers within the pyloric channel and first

portion of the duodenum usually are respon-

sible for outlet obstruction. Obstruction can

occur in an acute setting secondary to acute

inflammation and edema or, more commonly,

in a chronic setting secondary to scarring and

fibrosis. Helicobacter pylori has been

implicated as a frequent associated finding in

patients with GOO, but its exact incidence has

not been defined precisely.Within the pedi-

atric population, pyloric stenosis constitutes

the most important cause of GOO. Pyloric

stenosis occurs in 1 per 750 births. It is more

common in boys than in girls and also is more

common in first-born children. Pyloric steno-

sis is the result of gradual hypertrophy of the

circular smooth muscle of the pylorus. (See

image below). Anatomic changes associated

with pyloric stenosis. Pancreatic cancer is the

most common malignancy causing GOO.

Outlet obstruction may occur in 10-20% of

patients with pancreatic carcinoma. Other

tumors that may obstruct the gastric outlet

include ampullary cancer , duodenal cancer,

cholangiocarcinoma, and gastric cancer .

Metastases to the gastric outlet also may be

caused by other primary tumors. Management

of foreign-body ingestion is influenced by the

patient's age and clinical condition, the size,

shape and classification of the ingested

material, the anatomic location in which the

object is lodged and the technical abilities of

the endoscopist. Many reports discuss the

challenges of retrieving “sharp” foreign

objects, but the difficulty in managing large

foreign objects is less well described.If a

foreign body reaches the stomach, it will

likely pass without incident. However, there

are 3 sites where an object may fail to pass

once it has negotiated the esophagus: the

pylorus, the duodenal C-loop and the

ileocecal valve. Objects longer than 5 cm, or

more than 2.5 cm in diameter will have

difficulty passing through the pylorus.

Objects more than 10 cm long, such as a

toothbrush or a spoon, cannot negotiate the

duodenal C-loop secondary to its fixed

retroperitoneal position. In either case, these

objects should be endoscopically removed as

soon as possible to avoid pressure necrosis

and gastric perforation.4 If endoscopic

removal fails, surgery is warranted. Finally, if

the object successfully passes these potential

obstruction points, it can get lodged at the

ileocecal valve, the narrowest portion of the

small bowel. Surgical intervention may be

required if it has not passed within a week or

if the patient becomes symptomatic.(7)

References

1. Horton KM, Fishman EK. Current role of CT in

imaging of the stomach. Radiographics. 2003;23 (1):

75-87.

2. Gibson JB, Behrman SW, Fabian TC, Britt LG.

Gastric outlet obstruction resulting from peptic ulcer

disease requiring surgical intervention is infrequently

associated with Helicobacter pylori infection. J Am

Coll Surg. Jul 2000;191(1):32-7.

3. Gouma DJ, van Geenen R, van Gulik T, de Wit LT,

Obertop H. Surgical palliative treatment in bilio-

pancreatic malignancy. Ann Oncol. 1999;10 Suppl

4:269-72.

4. Alam TA, Baines M, Parker MC. The management

of gastric outlet obstruction secondary to inoperable

cancer. Surg Endosc. Feb 2003;17(2):320-3

5. Baron TH. Surgical versus endoscopic palliation of

malignant gastric outlet obstruction: big incision, little

incision, or no incision?. Gastroenterology. Oct

2004;127(4):1268-9

6. Huang YL, Lee HC, Yeung CY, et al. Sonogram

before and after pyloromyotomy: the pyloric ratio in

infantile hypertrophic pyloric stenosis. Pediatr

Neonatol. Jun 2009;50(3):117-20.

7. Shyr YM, Su CH, Wu CW, Lui WY. Prospective

study of gastric outlet obstruction in unresectable

periampullary adenocarcinoma. World J Surg. Jan

2000;24(1):60-4; discussion 64-5.

Review Article

Epidemiology and Current Management of Dyspepsia

MY Taher , H.Abazza ,Alexandria University

ABSTRACT

Dyspepsia is defined as chronic or recurrent pain or discomfort centered in the upper abdomen. Discomfort is defined as

a subjective negative feeling that is nonpainful, and can incorporate a variety of symptoms including early satiety or

upper abdominal fullness. Patients presenting with predominant or frequent (more than once a week) heartburn or acid

regurgitation should be considered to have gastroesophageal reflux disease (GERD) until proven otherwise. The

prevalence of dyspepsia varies considerably between different populations. Although these may represent genuine

epidemiological differences, the varying definitions used in different population studies may have contributed to this

discrepancy.

Using “upper abdominal pain” as the

definition

Prevalence of uninvestigated dyspepsia (UD)

has varied between 7%-34.2%., the lowest

UD prevalence of 7%-8% is seen in Singa-

pore, South East Asia, slightly higher rates are

seen amongst the Scandinavians (14.5% and

18.4% , prevalence rates of 23-25.8% are seen

in the US with populations in India (30.4%)

and New Zealand (34.2%) having the highest

rates. (1,2)

When a broader definition of upper

gastrointestinal symptoms is used

23%-45% prevalence of dyspepsia is

observed. Using this definition, a lower

prevalence is seen in Spain (23.9%), a 32%

UD prevalence rate in the US is noted, whilst

significantly higher rates of 38%-41% are

noted in the UK and 45% in Nigeria. (3)

Dyspepsia is a complex of symptoms refer-

able to the upper gastrointestinal (GI) tract.

Surveys have shown that dyspepsia is a global

problem with 15–40% of populations from

Asia to North America are complaining of

upper GI symptoms .All guidelines carried

out extensive reviews of the literature to

inform their recommendations. (4)The major-

ity used a definition of dyspepsia in line with

the Rome criteria. Current ACG, AGA and

Rome III guidelines;state that dyspepsia is

nonreflux predominant pain or discomfort in

the upper abdomen. Thus, symptoms below

the umbilicus or in the chest are inconsistent

with a diagnosis of dyspepsia. Yet the term

‘dyspepsia’ may carry other meanings in

clinical practice. However lifetime estimates

of dyspepsia ranged from 5 to 12% world

wide. It is estimated that between 25 and 40%

of individuals with dyspepsia will consult a

primary care physician as a result of their

symptoms. (5,6)

Burden of dyspepsia

The large burden of dyspepsia, including its

high population prevalence and impact on

quality of life, leads to over $14 billion

annually in direct costs of care. In light of this

high health economic burden, it is important

that providers follow ‘best practice’ evidence-

based management guidelines to improve

patient outcomes while minimizing resource

utilization. (7) Four major etiologies for dysp-

epsia include: Gastric and esophageal malig-

nancy, peptic ulcer disease, gastroesophageal

reflux disease (GERD), and functional dysp-

epsia, the latter occurring when epiga-stric

predominant symptoms are present in the

absence of a definite structural cause at upper

GI endoscopy (8,9)

Common Causes Of Dyspepsia Diagnosed

During Endoscopy(10)

The common diagnoses made at endoscopy in

all age groups are: - Diagnoses % (Duodenal

ulcer* 10-15, Gastric ulcer* 5-10, Oesophago

/Gastric Cancer* 2, Oesophagitis 10-17,

Gastritis*, Duodenitis* or Hiatus Hernia 30,

Normal 30) . *These conditions are strongly

associated with H.pylori Infection. 40 to 60%

of individuals presented with Dyspepsia,

have a normal endoscopic examination.The

impact of dyspepsia upon quality of life is a

personal experience; a recurring problem or a

chronic complaint for which available

treatments may be wholly effective or only

partially relieve symptom .Dyspepsia was not

associated with an increased mortality in the

community. Classification of dyspepsia: the

most common subgroups of dyspepsia

patients that have been described include ;

Uninvestigated dyspepsia which is classified

as a condition with characteristic symptoms

clinically assessed to be originating in the

upper Gastro Intestinal tract (UGI), but which

has not been recently investigated by UGI

endoscopy .Functional dyspepsia (sometimes

called non-ulcer dyspepsia) refers to a

situation where UGI endoscopy did not reveal

a potential cause for the dyspepsia. It is

generally reserved for patients with a normal

endoscopy whose symptoms do not suggest

GORD. Optimal approach to dyspepsia

remains controversial .(11)

Optimal approach to dyspepsia

Early dyspepsia guidelines recommended

antisecretories as the frist line of therapy.As

evidence mounted to suggest that

Helicobacter pylori eradication may relieve

many patients of their symptoms, subsequent

consensus guidelines suggested an H.

pylori‘test-and-treat’ approach for patients

with uncomplicated dyspepsia. Specifically,

the guidelines recommended that patients

with dyspepsia who are aged <45 years and

without alarm symptoms should be tested for

H. pylori and, if positive, receive a 10- to 14-

day course of eradication therapy. If

symptoms fail to improve with treatment,

then diagnostic upper endoscopy is indicated.

When to endoscope

Age >55 or alarm features (any age) are

considered an indication for endoscopic

examination. If Helicobacter . pylori

eradication and/or PPI fails in those ≤55 also

are indications for endoscopic examination in

dyspepsia patients

Place of H. pylori test and treat

H. pylori test and treat if prevalence >10%,

Empirical PPI in lower prevalence areas

should be the initial management .

Considering H. pylori test and treat if patient

fails empiric acid suppression and/or

prokinetic therapy .In areas with high

prevalence of H. pylori this strategy unlikely

to be beneficial

Use of PPI therapy

Empiric PPI therapy is the first line therapy

in low H. pylori prevalence areas or . After H.

pylori test is negative or positive and failing

treatment in high prevalence areas.Standard

doses of PPI therapy should be used with

double doses considered if symptoms persist (12).Several lines of evidence support the PPI

approach for dyspepsia, including: PPI

therapy, either alone or in combination with

H. pylori‘test-and-treat’. Meta-analysis reve-

als that PPI therapy is marginally superior to

H. pylori test-and-treat in the management of

functional dyspepsia Also data indicate that

empiric PPI therapy is superior to test-and-

treat for dyspepsia from underlying peptic

ulcer disease – another common etiology of

dyspeptic symptoms. PPI therapy is effective

in reducing dyspeptic symptoms in the setting

of NSAID therapy – an increasingly prevalent

risk factor for dyspepsia. In young patients

with uncomplicated dyspepsia, either H.

pylori ‘test and treat’ with PPI for those

testing negative, or empirical acid suppression

therapy are recommended as first-line

management strategies by all the guidelines,

depending on the prevalence of H. pylori in

the local population (13)

Conclusion

Dyspepsia is a common complaint, and the

management of the condition represents a

considerable financial burden for the health

service. spite the information contained in the

various guidelines, gaps in current knowledge

still exist.

References

1. Agreus L, Talley NJ, Svardsudd K, Tibblin G, Jones

MP. Identifyingdyspepsia and irritable bowel

syndrome: the value ofpain or discomfort, and bowel

habit descriptors. Scand J Gastroenterol 2000; 35: 142-

151

2. Haque M, Wyeth JW, Stace NH, Talley NJ, Green

R. Prevalence,severity and associated features of

gastro-oesophageal reflux and dyspepsia: a population-

based study. N Z Med J 2000; 113: 178-181

3. Ihezue CH, Oluwole FS, Onuminya JE, Okoronkwo

MO. Dyspepsias among the highlanders of Nigeria: an

epidemiological survey. Afr J Med Med Sci 1996; 25:

23-29

4. Caballero-Plasencia AM, Sofos-Kontoyannis S,

Valenzuela-Barranco M, Martin-Ruiz JL, Casado-

Caballero FJ, Lopez-Manas JG. Irritable bowel

syndrome in patients with dyspepsia: a community-

based study in southern Europe. Eur J

GastroenterolHepatol 1999; 11: 517-522

5. Moayyedi P, Forman D, Braunholtz D, Feltbower R,

Crocombe W, Liptrott M, Axon ATR: The proportion

of upper gastrointestinal symptoms in the community

associated with Helicobacter pylori , lifestyle factors,

and nonsteroidal anti-inflammatory drugs. Am J

Gastroenterol 2000; 95: 1448–1455.

6. Talley NJ, Colin-Jones DG, Koch KL, Koch M,

Nyren O, Stanghellini V: Functional dyspepsia: A

classification with guidelines for diagnosis and

management. GastroenterologyInt 1991; 4: 145–160

7. Talley NJ, Vakil N. Practice Parameters Committee

of the American College of Gastroenterology.

Guidelines for the management of dyspepsia. Am J

Gastroenterol2005; 100: 2324–37

8. Canga C, Vakil N. Upper GI malignancy,

uncomplicated dyspepsia, and the age threshold for

early endoscopy. Am J Gastroenterol ;2002; 97: 600–3.

9. Ford AC, Forman D, Bailey AG, Cook MB, Axon

AT, Moayyedi P: Who consults withdyspepsia?

Results from a longitudinal 10-yrfollow-up study. Am

J Gastroenterol 2007;102:957-965

10. Delaney BC Innes MA et al Initial Management

Strategies for Dyspepsia. The Cochrane Library, Issue

3, 2001 Oxford.

11. Lieberman D, Fennerty MB, Morris CD, Holub J,

Eisen G, Sonnenberg A: Endoscopicevaluation of

patients with dyspepsia: Results from the National

Endoscopic Data Repository.Gastroenterology 2004;

127: 1067–1075

12. Everhart JE, Ruhl CE. Burden of digestive diseases

in the United States Part 1: overall and upper

gastrointestinal diseases. Gastroenterology2009; 136:

376–86

13. Tack J, Talley NJ, Camilleri M, et al. Functional

gastroduodenal disorders. Gastroenterology2006; 130:

1466–79

Review Article

Restrictive Transfusion Strategy, Improved the Outcomes Among Patients with Acute Upper

Gastrointestinal Bleeding. (AUGIB)

MY Taher , Alexandria University

ABSTRACT

The goal of red-cell transfusions is to improve the delivery of oxygen to tissues. The safest and most effective

transfusion strategy depends not only on the hemoglobin trigger level but also on factors such as coexisting conditions,

age, and hemodynamic status (1)

Acute upper gastrointestinal bleeding

(AUGIB) accounts for 25% of RBC units

transfused in the Egypt ,due to the high

prevalence of portal hypertension bleeding

form varices and gastropathy. A restrictive

strategy of red-cell transfusion is at least as

effective as and possibly superior to a liberal

transfusion strategy in critically ill patients,

with the possible exception of patients with

acute myocardial infarction and unstable

angina.Acute upper gastrointestinal bleeding

is a common emergency condition associated

with high morbidity and mortality.1 It is a

frequent indication for blood transfusion,

because acute blood loss can decrease tissue

perfusion and tissues oxygenation . Trans-

fusion may be lifesaving in patients with

massive bleeding. However, in most cases

hemorrhage is not so severe, and in such

circumstances the safest and most effective

transfusion strategy is controversial.(2,3) Restr-

icted transfusion strategies may be appro-

priate in some settings. Controlled trials have

shown that for critically ill patients, a restri-

ctive transfusion strategy is at least as effect-

tive as a liberal strategy, while substantially

reducing the use of blood supplies . The most

relevant finding was the improvement in

survival rates observed with the restrictive

transfusion strategy.The optimal hemoglobin

threshold for erythrocyte transfusions in

critically ill children is unknown. We hypo-

thesized that a restrictive transfusion strategy

of using packed red cells that were leukocyte-

reduced before storage would be as safe as a

liberal transfusion strategy, as judged by the

outcome of multiple-organ dysfunction. (4,5)

However, these studies excluded patients with

gastrointestinal bleeding. Observational stud-

ies and small controlled trials have suggested

that transfusion may be harmful in patients

with hypovolemic anemia,6,7 even in those

with gastrointestinal bleeding. (6,7,8) Trans-

fusion policy aimed at completely replacing

blood loss worsens the magnitude of bleeding

and mortality from portal hypertensive-related

bleeding in cirrhotic rats. On the contrary,

moderate blood transfusion allowed hemo-

dynamic stabilization and increased survival.

Early blood transfusion transfusion in Acute

Upper Gastroiintestinal bleeding (AUGIB)

was associated with a two-fold increased risk

of re-bleeding and an increase in mortality,

although the latter was not statistically

significant. Early blood transfusion appears to

reverse the hypercoagulable response to

haemorrhage thereby encouraging re-bleeding

and hence the need for an operation(7,8,9,10)

Among patients with severe acute upper

gastrointestinal bleeding, the outcomes were

significantly improved with a restrictive trans-

fusion strategy, in which the hemoglobin

threshold was 7 g per deciliter, as compared

with a liberal transfusion strategy, in which

the hemoglobin threshold was 9 g per

deciliter. Transfusion requirements may be

different for patients with acute hemorrhage

due to factors such as hemodynamic insta-

bility or rapid onset of anemia to extremely

low hemoglobin levels. Current international

guidelines recommend decreasing the he-

moglobin threshold level for transfusion in

patients with gastrointestinal bleeding, from

10 g per deciliter to 7 g per deciliter. A

reduction in the number of transfusions

performed may have accounted for the

reduction in mortality from gastrointestinal

bleeding that has been observed in recent

years. Cardiac complications, particularly

pulmonary edema, occurred more frequently

with the liberal transfusion strategy, both in

the current study and in the trial that involved

critically ill adults.4 The higher level of

cardiac complications may indicate a higher

risk of circulatory overload associated with a

liberal transfusion strategy. Other effects of

transfusion, such as transfusion-related

immunomodulation, may increase the risk of

complications or death. Adverse outcomes

have also been associated with long storage

time of transfused blood. , storage lesions

become apparent after about 14 days. The risk

of further bleeding, the need for rescue

therapy, and the rate of complications were all

significantly reduced, and the rate of survival

was increased, with the restrictive transfusion

strategy.(11) Allogeneic blood transfusion

(ABT)-related immunomodulation (TRIM)

encompasses the laboratory immune aberr-

ations that occur after ABT and their

established or purported clinical effects.

TRIM is a real biologic phenomenon resulting

in at least one established beneficial clinical

effect in humans, but the existence of

deleterious clinical TRIM effects has not yet

been confirmed. Initially, TRIM encompassed

effects attributable to ABT by immunom-

odulatory mechanisms (e.g., cancer recur-

ence, postoperative infection, or virus

activation). More recently, TRIM has also

included effects attributable to ABT by pro-

inflammatory mechanisms (e.g., multiple-

organ failure or mortality). TRIM effects may

be mediated by: (1) allogeneic mononuclear

cells; (2) white-blood-cell (WBC)-derived

soluble mediators; and/or (3) soluble HLA

peptides circulating in allogeneic plasma (12)

Reference

1. Gralnek IM, Barkun AN, Bardou M. Management of

acute bleeding from a peptic ulcer. N Engl J Med

2008;359:928-937

2. Barkun AN, Bardou M, Kuipers EJ, et al.

International consensus recommendations on the

management of patients with nonvariceal upper

gastrointestinal bleeding. Ann Intern Med

2010;152:101-113

3. Barkun A, Bardou M, Marshall JK. Consensus

recommendations for managing patients with

nonvariceal upper gastrointestinal bleeding. Ann Intern

Med 2003;139:843-857

4. Lacroix J, Hebert PC, Hutchison JS, et al.

Transfusion strategies for patients in pediatric intensive

care units. N Engl J Med 2007;356:1609-1619

5. Kravetz D, Sikuler E, Groszmann RJ. Splanchnic

and systemic hemodynamics in portal hypertensive rats

during hemorrhage and blood volume restitution.

Gastroenterology 1986;90:1232-1240

6. Castaneda B, Morales J, Lionetti R, et al. Effects of

blood volume restitution following a portal

hypertensive-related bleeding in anesthetized cirrhotic

rats. Hepatology 2001;33:821-825

7. Blair SD, Janvrin SB, McCollum CN, Greenhalgh

RM. Effect of early blood transfusion on

gastrointestinal haemorrhage. Br J Surg 1986;73:783-

785

8. de Franchis R. Updating consensus in portal

hypertension: report of the Baveno III consensus

workshop on definitions, methodology and therapeutic

strategies in portal hypertension. J Hepatol

2000;33:846-852

9. British Society of Gastroenterology Endoscopy

Committee. Non-variceal upper gastrointestinal

haemorrhage: guidelines. Gut 2002;51:Suppl 4:iv1-iv6

10. Crooks C, Card TIM, West J. Reductions in 28-day

mortality following hospital admission for upper

gastrointestinal hemorrhage. Gastroenterology

2011;141:62-70

11. Vamvakas EC, Blajchman MA. Transfusion-related

immunomodulation (TRIM): an update. Blood Rev

2007;21:327-348,12Lacroix J, Hebert PC, Hutchison

JS, et al. Transfusion strategies for patients in pediatric

intensive care units. N Engl J Med 2007;356:1609-

1619

Case Report

Permeated Surgical Gauze after Open Cholecystectomy Presented as Gastric

Outlet Obstruction (GOO)

M Y Taher*,Wael Nabil**

Alexandria University HPB Unit* and surgical department **

ABSTRACT

Intraperitoneal foreign body erodes through duodenal wall, usually erosion, ulceration, bleeding, fistula, abscess,

obstruction, foreign body granuloma may be formed.We presnt a cse of missed surgical towel that eroded into the

duodenum and presented with a picture of gastric outlet obstruction.

Case presentation: 42 year Female patient

presented with persistent vomiting for six

months after doing open cholecystectomy for

gall stones. Clinically the patient was

dehydrated ,and slightly anemic She gave

history persistent upper abdominal pain since

she was submitted to cholecystectomy .

Immediately after surgery she suffered

recurrent attacks of fever that responded to

antibiotics .Recently she started to suffer

from persistent vomiting and was referred for

upper gastrointestinal endoscopic examin-

ation. On doing endoscopy a gauze surgical

towel was permeated and adherent to the

duodenal wall at the beginning of the descen-

ding duodenum and obstructing it completely

.The surgical towel was removed during

endoscopy .We assured patency of the duo-

denum. surprisingly there no evidence of any

erosions, ulcerations or abscess formation.

Permeated surgical gauze in the duodenum

Surgical gauze obstructing the duodenum

Surgical towel after extraction

Review of the literature

Foreign body impaction after oral intake is

associated with gastrointestinal obstruction

rarely. But transmural migration of foreign

body causing obstruction is very rare. If

intraperitoneal foreign body erodes through

duodenal wall, usually erosion, ulceration,

bleeding, fistula, abscess, obstruction, foreign

body granuloma may be formed. But in our

case, foreign body migration occurred leaving

no evidence of erosion, ulcer, bleeding, fistula

or abscess. (1,2) Despite migration of large

foreign bodies, abscess or peritonitis may not

be manifested clinically.Even more on explo-

ration no signs of migration might be found

on serosal surfaces.Ultimate manifestation i.e.

gastric outlet obstruction might be the only

finding. (3,4) Retained surgical sponges are

the most common postoperative intraabd-

ominal foreign bodies .Pathological responses

may be aseptic fibrinous leading to encap-

sulation, adhesion and granuloma formation

or exudative leading to abscess forma-

tion.More complications are observed in

exudative type. The common ones are bowel

obstruction , perforation, pseudotumor, granu-

lomatous peritonitis, bleeding. The low index

of suspicion due to rarity to the condition and

long latency in the manifestation of the

symptoms frequently leads to delay in

diagnosis or missed diagnosis till laparotomy

or endoscopic examination (5,6). In the

present case the patient presented 6 months

after open cholecystectomy by gastric outlet

obstruction

References

1. Rappaport W, Haynes K: The retained surgical

sponge following intra-abdominal surgery. A

continuing problem. Arch Surg 1990, 125:405-407.

2. Kiernan F, Joyce M, Byrnes CK, O’Grady H, Keane

FB, Neary P: Gossypiboma: a case report and review

of the literature. Ir J Med Sci 2008, 177:389-391.

3. Silva CS, Caetano MR, Silva EA, Falco L, Murta

EF: Complete migration of retained surgical sponge

into ileum without sign of open intestinal wall. Arch

Gynecol Obstet 2001, 265:103-104.

4. Wig JD, Goenka MK, Suri S, Sudhakar PJ, Vaiphei

K: Retained surgical sponge: an unusual cause of

intestinal obstruction. 4-J Clin Gastroenterol 1997,

24:57-58.

5. Lourenco SC, Baptista A, Pacheco H, Malhado J: A

misplaced surgical towel - a rare cause of fever of

unknown origin. Eur J Intern Med 2008, 19:377-378.

6. Tumer AR, Yasti AC: Medical and legal evaluations

of the retained foreign bodies in Turkey. Leg Med

(Tokyo) 2005, 7:311-313.

Original Article:

Relation Of Pretreatment Serum B12 Level And Response To Treatment With

Interferon And Ribavirin In Patients With Chronic HCV Infection

Khaled Mahmoud Mohiedeen and Akram deghedy*

Tropical medicine and clinical pathology* department, alexandria faculty of medicine

ABSTRACT

Background: Given the poor prognosis and high cost of effective treatments for HCV, it appears important to

determine factors that may predict favorable response to interferon based treatment and examine complementary

medicine treatment possibilities. Objective: to evaluate the relation of pretreatment serum level of vitamin B12 and the

end of treatment response. Methods: This study included fifty treatment naïve HCV patients who were legible to be

treated with pegylated interferon and ribavirin in patients with chronic HCV infection. Serum B12 was analyzed in

samples collected before treatment start. Pretreatment serum B12 levels were correlated to the response of treatment.

Results: Pretreatment vitamin B12 measurement showed a significant difference between those who respond to

treatment and those who failed to respond to interferon based treatment. The mean value of serum B12 vitamin in non

responders was (267.286+ 29.69) which was significantly less than those who respond to treatment (332.167+ 49.05)

(P< 0.00001). There was no significant difference regarding pretreatment viral load in both responders and non-

responders. Conclusion: Pretreatment serum B12 level measurement can be used as a predictor of response to treatment

in HCV patients.

Introduction

The hepatitis C virus (HCV) is an important

human pathogen, infecting about 1% of the

global population. Approximately 30% of

chronically infected carriers develop serious

liver disease, making it the single leading

indicator for liver transplantation (1). Given

the poor prognosis and paucity of effective

treatments for HCV, it appears important to

examine complementary medicine treatment

possibilities. Vitamin B12 is stored in hepato-

cytes and inhibits hepatitis C virus (HCV)

RNA translation. (2) Vitamin B12 (100 mcg

IM four times daily) was reported to be of

benefit in the treatment of acute hepatitis (3).

Some authors suggested that serum levels of

vitamin B12 may be among the factors that

can help predict whether patients with chronic

hepatitis C virus (HCV) infection will resp-

ond to interferon-based treatment.(4) However,

the implication of B12 in the setting of

antiviral treatment is still unclear and needs

further clarification especially for Egyptian

patients infected with HCV genotype 4.

Aim of the work

This study aimed to correlate pretreatment

B12 serum level with end-of-treatment

response in patients with chronic HCV to

evaluate the role of serum B12 level

measurement as a predictor of response to

treatment in HCV patients.

Subjects

This study included fifty treatment naïve

HCV patients who were legible to be treated

with pegylated interferon and ribavirin acco-

rding to the criteria adopted by the Ministry

of Health. Patients were enrolled in the study

after obtaining their consent. Patients were

grouped according to their response to

treatment into: Group (1): Responders, those

who have sustained viral response (SVR)

defined as undetectable serum HCV RNA six

months after the completion of treatment.

Group (2): Non - Responders, those who

failed to clear HCV RNA from their sera.

They may belong to one of the following

categories: Null response: Failure to reduce

HCV RNA by at least 2 logs10 (100 times)

after 12 weeks of treatment. Breakthrough:

After dropping to undetectable levels, HCV

RNA is detected again in blood during

treatment. Relapse: After dropping to unde-

tectable levels, HCV RNA is detected again

in blood after treatment ends.

Methods

All patients were subjected to thorough

history taking and clinical examination,

routine laboratory investigations including:

CBC, urine, stool and liver function tests.

Diagnosis of chronic HCV infection was

confirmed by the detection of anti HCV

antibodies as well as the HCV RNA in serum

by RT-PCR using the Amplicor HCV 2.0

assay (Roche Diagnostics). Patients who

fulfilled the criteria for eligibility to receive

interferon based therapy adopted by the

Ministry of Health were enrolled in this study.

Patients were followed up during the

treatment period and viral load was deter-

mined at weeks 12, 24, 36, at the end of

treatment at week 48 and six months later.

Patients who had to stop treatment for

intolerable side effects were excluded from

the study. Serum B12 was analyzed in

samples collected before treatment start.

Aliquots of whole blood were collected and

centrifuged and the serum was separated and

frozen at -20 Co for subsequent determination

of vitamin B12. Serum vitamin B12

concentration was assayed by an automated

chemiluminescent competitive protein-

binding assay and acridine substrate (ADVIA

Centaur System, Bayer, Germany). The

results were expressed as pmol/L. Pret-

reatment serum B12 levels were correlated to

the response of treatment.

Results

Fifty treatment naïve HCV patients were

included in the study. The characteristics of

the patients are presented in Table 1. Subjects

had a mean age of 44.4 years; there were 33

men and 17 women. Pretreatment viral load

ranged between 123,000 and1,280,000 IU/ml

with a mean of 609,806 + 307,463 IU/ml.

Three patients enrolled in the study were

excluded later on owing to the occurrence of

intolerable side effects. Regarding response to

treatment (Table.2), thirty eight patients

(76%) showed response to antiviral treatment

at the end of treatment with clearance of viral

RNA from the sera. Fourteen patients (28%)

were considered non responders; four of them

showed null response (8%), eight patients

(16%) had a breakthrough during treatment.

However, two patients (4%) failed to have a

sustained viral response (SVR) to treatment

with reemergence of viral RNA six months

after stoppage of treatment and considered as

relapsers. Pretreatment vitamin B12 meas-

urement (Table .3) showed a significant

difference between those who respond to

treatment and those who failed to respond to

interferon based treatment. The mean value of

serum B12 vitamin in non responders was

(267.286+ 29.69) which was significantly less

than those who respond to treatment

(332.167+ 49.05) (P< 0.00001). There was no

significant difference regarding pretreatment

viral load in both responders and non-

responders.

Table.1 Patients demographic characteristics

Age Range: 29 - 56

Mean: 44.4 y

Sex Males: 33

Females: 17

viral load at the start of

treatment

Range: 123.000 – 1.280.000 IU/ml

Mean: 609,806 + 307,463

Table .2 Patients response to treatment

Type of

response

Responders

(At the end of

treatment)

SVR

Non Responders

Null Response Breakthrough Relapsers

N 38 (76%) 36 (72%) 4 (8%) 8 (16%) 2 (4%)

Table.3 Mean value of pretreatment serum B12 and viral load in both responders and non responders

Responders Non- responders P value

Mean value of pretreatment serum

B12 (pmol/L) 332.167 + 49.05 267.286 + 29.69

P< 0.00001

Significant

Mean value of pretreatment viral

load (IU/) 601,136.9 + 281,425 633,071.4 + 377,289

P = 0.7839

Insignificant

Discussion

Hepatitis C virus (HCV) is a major pathogen

of chronic hepatitis and leads to fatal liver

diseases, such as liver cirrhosis and hepato-

cellular carcinoma. (5) Approximately 170

million people worldwide are infected with

HCV. (6) The combination of pegylated

interferon (IFN) with ribavirin is currently the

most effective therapy for chronic hepatitis C. (7) However, the SVR rate still remains at

approximately 55%. (8) Therefore, it remains

necessary to identify alternative agents that

have fewer side effects to couple with IFN. In

developing countries, it is difficult to

administer expensive IFN therapy. Hence, in

such countries, inexpensive anti-HCV reag-

ents are especially desirable. (9) Some resear-

chers tried to study the relationship between

various nutrients and HCV replication. Yano

et al (10) found that among the ordinary

nutrients tested, β-carotene, vitamin D2, and

linoleic acid possessed anti-HCV activity in a

cell culture system, and they suggested that

these nutrients are therefore considered to be

potential candidates for enhancing the effects

of interferon therapy. Other study suggested

that adding vitamin D to conventional Peg-α-

2b/ribavirin therapy for treatment-naïve pati-

ents with chronic HCV genotype 1 infection

significantly improves the viral response. (11)

In the present study, pretreatment vitamin

B12 measurement showed a significant differ-

ence between those who respond to treatment

and those who failed to respond to interferon

based treatment. The mean value of serum

B12 vitamin in non responders was signific-

antly less than those who respond to treat-

ment. This is in accordance with the results

reported by Rosenberg et al (4) who reported

that serum B12 more than 360 pm is indep-

endently correlated to end of treatment respo-

nse in HCV patients treated with interferon

and ribavirin. They suggested that association

between high pretreatment serum B12 and

favorable response to treatment is due to

involvement of vitamin B12 in suppression of

viral replication during anti-HCV treatment.

Lott et al (2) showed that cyanocobalamin

(vitamin B12) inhibited HCV replication

through its inhibitory effect on the HCV

internal ribosome entry site (IRES)-dependent

translation in vitro in a dose-dependent man-

ner. This relationship was not reported when

other viruses were studied. The role of vita-

min B12 in the inhibition of HCV replication

was also documented by Li et al. (12) These

results should be implemented into a treatm-

ent strategy especially in the light of a recent

pilot study which concluded that Vitamin B12

supplementation significantly improves SVR

rates in HCV-infected patients naïve to antiv-

iral therapy.(13) This recent pilot study found

that adding vitamin B12 to standard therapy

strengthened the rate of sustained viral respo-

nse by 34%, the The findings showed that the

effect of vitamin B12 was particularly strong

in patients whose infection was proving diffi-

cult to treat effectively. While trials of new

generation antiviral drugs show promise, they

are expensive, and can make treatment more

difficult. And questions still remain about

how well they will work in practice. Rocco et

al concluded that until clear eligibility criteria

for treatment with the new generation anti-

viral drugs are established, standard treatment

plus vitamin B12 is a safe and inexpensive

alternative, particularly for those who carry a

strain of the virus that is hard to treat.

References

1. J A Cuthbert. Hepatitis C: progress and problems.

Clin Microbiol Rev. 1994; 7(4): 505-32

2. Lott WB, Takyar S, Tuppen J, Crawford DHG,

Harrison M. Sloots TB, Gowans EJ Vitamin B12 and

hepatitis C: Molecular biology and human pathology.

Proc Natl Acad Sci U S A. 2001; 98(9): 4916–4921.

3. Spellberg MA. The treatment of viral hepatitis. Am J

Gastroenterol 1969;51:15-34

4. Rosenberg P, Hagen K. Serum B12 Levels Predict

Response to Treatment with Interferon and Ribavirin in

Patients with Chronic HCV Infection. J Viral

Hepat.2011;18(2):129-34

5. Liang TJ, Jeffers L J, Reddy K R, De Medina M,

Parker I T, Cheinquer H, Idrovo V, Rabassa A, and

Schiff ER. Viral pathogenesis of hepatocellular

carcinoma in the United States. Hepatology 1993;

18:1326-33.

6. Wasley A, Alter M J.. Epidemiology of hepatitis C:

geographic differences and temporal trends. Semin

Liver Dis 2000; 20:1-16

7. McHutchison J G, Fried MW. Current therapy for

hepatitis C: pegylated interferon and ribavirin. Clin.

Liver Dis 2003; 7:149-161.

8. Hadziyannisn SJ, Sette Jr H, Morgan T R, Balan V,

Diago M, Marcellin P, Ramadori G, Bodenheimer Jr

H, Bernstein D, Rizzetto M, Zeuzem S, Pockros P J,

Lin A, Ackrill A M. Peginterferon-alpha2a and

ribavirin combination therapy in chronic hepatitis C: a

randomized study of treatment duration and ribavirin

dose. Ann. Intern. Med. 2004;140:346-355.

9. Sagoe-Moses C, Pearson R D, Perry J, Jagger J.

Risks to health care workers in developing countries.

N. Engl. J. Med. 2001; 345:538-541.

10. Yano M, Ikeda M, Abe K, Dansako H, Ohkoshi S,

Aoyagi Y, Kato N. Comprehensive Analysis of the

Effects of Ordinary Nutrients on Hepatitis C Virus

RNA Replication in Cell Culture. Antimicrob Agents

Chemother. 2007 ; 51(6): 2016–27

11. Abu-Mouch S, Fireman Z, Jarchovsky J, Zeina A,

Assy N. Vitamin D supplementation improves

sustained virologic response in chronic hepatitis C

(genotype 1)-naïve patients. World J Gastroenterol.

2011; 17(47): 5184–5190.

12. Li D, Lott WB, Martyn J, Haqshenas G, Gowans

EJ. Differential effects on the hepatitis C virus (HCV)

internal ribosome entry site by vitamin B12 and the

HCV core protein. J Virol. 2004 ;78(21):12075-81.

13. Rocco A, Compare D, Coccoli P, Esposito C, Di

Spirito A, Barbato A, Strazzullo P, Nardone G.

Vitamin B12 supplementation improves rates of

sustained viral response in patients chronically infected

with hepatitis C virus. Gut. 2012 Jul 17. [Epub ahead

of print]

Original Article

Dual Impact of Chronic Hepatitis C and Schitosomal Hepatic Fibrosis on Gall

Bladder Disease

Fathia E Asal1, Ahmed Khalid Tawfik1, Raafat A Salah1 & Abdelmonem N Darwish2

Tropical Medicine1 and Diagnostic Radiology2 Departments, Faculty of Medicine, Tanta University, Egypt

ABSTRACT

Background/Aim: Hepatitis c virus is recognized as a major threat to global public health. An estimated 200 million

people worldwide are infected .Gall bladder disease represents one of the most common and costly of all digestive

diseases. The aim of the work is to study gallbladder disease in chronic hepatitis c patients. Patients & methods: This

study included 180 patients and 40 healthy individuals. They were classified into five groups namely: Group 1: included

78 patients associated with chronic hepatitis C without cirrhotic changes. Group II: included 22 patients with chronic

hepatitis c patients with cirrhotic changes. Group III: included 40 patients without HCV infection but associated with

gallbladder disease. Group IV: included 40 patients with schistosomal infection and pure hepatic periportal fibrosis

without HCV infection. Group V: included 40 healthy individuals. All patients and controls were submitted to total

serum cholesterol, determination of serum estradiol (E2) and abdominal ultrasonogrophy for estimation of gallbladder

volume & periportal fibrosis. Fasting and postprandial volumes of GB and ejection fraction were measured. Results:

Chronic HCV infection is an important risk factor for gall bladder disease in Egypt. Among persons with HCV

infection, the prevalence of gall bladder disease is highest among those with more severe liver disease. This study also

demonstrates that obesity represents one of the most important risk factors for gallbladder stones formation in non

hepatitis c patients. This study also demonstrates that schistosomiasis represents a risk factor for gallbladder stones

formation. Conclusion: Schistosomiasis represents a risk factor for gallbladder stones formation. Also, People with

chronic Hepatitis C are at a greater risk for developing gallbladder disease; so those patients are strongly encouraged to

practice gallstone prevention.

Introduction

Hepatitis C virus (HCV) is a major cause of

progressive liver disease with approximately

170 million people infected worldwide. HCV

induces chronic infection in up to 80% of

infected individuals. The main complications

of HCV infection are liver fibrosis and

cirrhosis, and 30-50% of individuals with

cirrhosis develop hepatocellular carcinoma(1,

2). Gall stones are a major public health

problem, and represent one of the most

common and costly of all digestive diseases.

Although liver cirrhosis is a well-documented

risk factor for the formation of gall stones,

little is known about the prevalence of gall

bladder disease (GBD) in persons with

chronic hepatitis C virus (HCV) infection(3).

Both impaired gall bladder epithelium lipid

absorption or gall bladder muscle contractility

are factors associated with GBS (gall bladder

stones) formation(4). Because HCV-RNA can

be detected in gall bladder cell culture for up

to 35 days, potentially HCV may impair or

alter gall bladder function and contribute to

the development of GBS. Alternation of bile

lipid composition also contributes to GBS

formation(5). The HCV may bind to lipo-

protein and induce fatty change of liver(6).

Apolipopotein E polymorphism is associated

with GBS formation(7) and severity of HCV

infection and hyperlipidemia after interferon

treatment for chronic hepatitis C(8). The aim

of this work is to study gall bladder disease in

chronic hepatitis C virus patients.

Patients & Methods

This study included 180 patients and 40

healthy individuals randomly selected from

patients admitted to Tropical Medicine Depar-

tment, Faculty of Medicine, Tanta University,

and from patients attending the out clinic.

They were classified into five groups namely:

Group 1: included 78 patients with chronic

hepatitis C without cirrhotic changes. Group

II: included 22 patients with chronic hepatitis

C patients and cirrhotic changes. Group III:

included 40 patients with gall bladder disease

but without HCV infection. The presence of

gall bladder disease was ascertained by

ultrasonographic evidence of gallbladder

stones or cholecystectomy. Group IV: incl-

uded 40 patients with schistosomal infection

and pure hepatic periportal fibrosis without

HCV infection. Group V: included 40 healthy

individuals. Patients with diabetes mellitus,

other viral infections as hepatitis B virus and

patients with renal failure were excluded from

the study. All patients and controls included

in this study were submitted to full history

talking, clinical examination; with calculation

of body mass index [according to the

equation: body mass index= weight (Kg)

/height2 (m2)(9). Then all cases were subjected

to: Routine investigations: as urine & Stool

analysis for diagnosis of schistosomiasis,

complete blood picture, Liver function tests

and serum cholesterol. Also we performed

anti-HCV using second generation (ELISA),

PCR for HCV, Serum examination for

HBsAg to exclude HBV infection. Rectal

snips were taken to confirm schistosomal

infection. Determination of serum estradiol

(E2): according to the method describrd by

Rad Wanska E, et al,(10). 3-Abdominal

ultrasonogrophy: Real time ultrasonography

was used (Toshiba & Fukuda 4100) 3.5 MHz

with convex probe. The patient was fasting

for at least 8 hour before examination.

Diagnosis of liver cirrhosis was made

according to the ultrasonographic scoring

method, in which a score >8 was considered

diagnostic for liver cirrhosis, as proposed by

Lin et al(11). Gall bladder scanning; Choleli-

thiasis was diagnosed in the presence of one

or more of the following ultrasonographic

findings suggested by Barbara L et al,

(1987)(12): One or more echogenic, distally

shadowing, possible movable structures

within the gall bladder. One or more echog-

enic movable but not shadowing structures

within the gall bladder. Echogenic structures

with constant shadowing in the region of the

gall bladder fossa, with little or no

visualization of the gall bladder. Measu-

rement of gall bladder volume by ultrasound:

After fasting for at least 8 hr, the basal

gallbladder volumes were measured in the

supine or left lateral decubitus position by

ultrasonography with a 3.5-MHz convex

probe in all subjects. The volumes were

measured by the ellipsoid method using the

following formula (13): (Volume = 0.52 ×

length × width × height). Longitudinal and

axial cross-sectional images of the gallbladder

were made in triplicate, so as to obtain

maximal gallbladder length and width.

Transverse images were obtained at the site of

maximal gallbladder width and longitudinal

images through the long axis of the

gallbladder.

Measurement of gall bladder length

Width (white arrows) and height (black arrows) of

the gallbladder

After that, gall bladder ultrasonography was

performed with the patient lying in the same

position 60 min after eating a mixed meal

consisting of one slice of bread 30 gm, 10 gm

butter, one boiled egg, 300 ml tea with 25 gm

sucrose. This was equivalent to 14 gm fat and

465 kcal according to Acalovschi M et al,

1997 (14). The gall bladder volumes were

expressed as absolute value in milliliters. So,

we could calculate the gall bladder volumes

(fasting and post-prandial), and in term we

could calculate the ejection fraction of the gall

bladder for each subject as follows: Ejection

fraction = (fasting - post prandial gall bladder

volume/fasting GB volume) x100 (15).

Results

(Table 1): Mean serum bilirubin, ALT, AST, cholesterol, albumin in the five groups.

GI

Mean+SD

GII

Mean+SD

Group III

Mean+SD

Group IV

Mean+SD

Group V

Mean+SD F.test p. value LSD

Bil.

mg/dl 1.98 + 0.21 2.5 + 0.28 0.9 +0.02

0.8

+0.01 0.7 +0.01 21.70 <0.05*

(GI.,GII)

(GI.,GIII)

(GI., GIV)

(GI.,GV)

ALT

IU 36 + 4.36 33 + 8.3 13 +5.3 14 +5 9 + 2.1 15.53 <0.001*

(GI.,GII)

(GI.,GIII)

(GI.,GIV)

(GIV.,GII)

AST

IU

35 + 3.28 31 + 4.5 12 +4.9 11 +4.7 8 +2.9 14.96 <0.001*

(GI.,GII)

(GI.,GIII)

(GI.,GIV)

(GIV.,GII)

(GII.,GV)

Chol.

mg/dl 176.2+ 28.3 164.3+42.6 21.50 + 46.5 184.1 + 24.3 173.7+ 37.1 10.241 <0.001*

(GI.,GII)

(GI.,GIII)

(GII.,GIII)

(GII.,GIV)

(GIII,GIV)

(GIII.,GV)

Alb.

gm/dl 4.50 + 1.37 2.7+ 0.68 4.3 + 0.22 4.7 + 1.2 4.9+ 1.02 1.98 <0.05*

(GI.,GII)

(GII.,GV)

(GII.,GIV)

(GII.,GIII)

Table (2): Mean fasting and one hour post prandial gallbladder volume (ml) in the five groups.

GI GII G III G IV

G V

Fasting 93ml+/-SD8.3 97ml+/-SD11.2 78.2ml+/-SD12.5 81.3ml+/-SD5.6 82.6ml+/-SD9.2

Post prandial 55.2ml+/-SD7.4 60.9+/-SD8.8 49.3ml+/-SD9.2 40.4ml+/-SD6.4 18.1ml+/-SD5.4

F. test 11.26

p. value 0.044*

LSD GI

GII 0.214

GII

GI 0.214

GIII

GI 0.093

Odd's ratio

14.362

GIII 0.043* GIII 0.637 GII 0.139

GIV 0.009* GIV 0.036* GIV 0.035*

GV 0.054 GV 0.187 GV 0.009*

Significant (< 0.05).

0

10

20

30

40

50

60

70

80

90

100

ml

Group I Group II Group III Group IV Group V

FGBV PPGBV

Fig. (1): Mean fasting and one hour post prandial gallbladder volume (ml) in the five groups.

Table (3): Mean ejection fraction in the five groups.

GI GII Group III Group IV Group V

Range 29-62 21-54 24 – 84.60 22 - 81 32 – 71.40

Mean 40.6% 37.2% 37% 50.34% 62.87%

+SD 11.28 12.5 18.57 15.75 11.01

F. test 12.365

p. value <0.002*

LSD GI

GII 0.436

GII

GI 0.436

GIII

GI 0.047*

Odd's ratio

18.32

GIII 0.047* GIII 0.645 GII 0.645

GIV 0.007* GIV 0.001* GIV 0.000*

GV 0.000* GV 0.000* GV 0.000*

Table (4): Mean serum estradiol (pg/ml) concentration in the five groups.

GI GII Group III Group IV Group V

Range 20-29 39-62 20 – 75.40 20 – 33 20 – 53

Mean 22pg/ml 54pg/ml 26.88 (pg/ml) 20.43 (pg/ml) 20.82(pg/ml)

+SD 9.58 23.6 14.30 2.10 5.21

F. test 4.235

p. value 0.033*

LSD GI

GII 0.006*

GII

GI 0.006*

GIII

GI 0.019*

Odd's ratio

23.351

GIII 0.019* GIII 0.013* GII 0.013*

GIV 0.211 GIV 0.002* GIV 0.047*

GV 0.206 GV 0.004* GV 0.049*

( *) Significant relation (< 0.05)

Discussion

Although liver cirrhosis is a well-documented

risk factor for the formation of gallstones,

little is known about the prevalence of

gallbladder disease (GBD) in persons with

hepatitis C virus (HCV) infection. This study

included 180 patients and 40 healthy controls,

divided into five groups, group I represented

(HCV) patients without cirrhosis, Group II

represented patients with chronic HCV with

cirrhosis, group III represented patients with

gallbladder disease without HCV, group IV

represented patients with pure schistosomal

periportal fibrosis, group V represented

normal controls. Gall bladder epithelial cells

are capable of both fluid absorption and

secretion (16). Both impaired gall bladder

epithelium lipid absorption or gall bladder

muscle contractility are factors associated

with GBS formation (4) .Because HCV-RNA

can be detected in gallbladder cell culture for

up to 35 days, other investigators have also

detected HCV RNA and HCV antigens in

gallbladder specimens obtained from HCV-

infected patients at the time of autopsy (17).

Potentially, HCV may impair or alter gall

bladder function and contribute to the

development of GBS (18). Alternation of bile

lipid composition also contributes to GBS

formation (19). The HCV may bind to

lipoprotein and induce fatty change of liver.

Apolipopotein E polymorphism is associated

with GBS formation (7). It is possible that

HCV infection might facilitate GBS

formation by altering bile composition, so

direct infection of the gall bladder by HCV

may play an important role in the

development of GBD. In patients with chronic

HCV with cirrhosis (group II) we found that

the prevalence of gall bladder disease was

54.5% (12/22) and the ejection fraction was

37.2% with SD +/-12.5. And it has been noted

that the prevalence was significantly higher in

group II (54.5%) than group I (12.8%) (X2 =

9.50 & P value 0.008) denoting that cirrhosis

is a major risk factor for gall bladder disease.

Also we found that the ejection fraction in

group II was significantly lower than that of

group IV (patients with pure periportal

fibrosis) and group V (control group) as P.

value< 0.001. While the difference between

the mean ejection fraction in cirrhotic & non

cirrhotic in group I was non significant (T test

= 1.46 & P. value = 0.146). These results

were higher than that of Conte De et al (1999) (20) who reported that 29.5% of cirrhotic

patients had gall stones. The higher preva-

lence (54.5%) in our study may be due to that

most of our patients were classified as grade

C according to Modified Child-Pugh classi-

fication. These results were in accordance

with Edmund et al (2005) (21) who found that

stone formation was increased with advanced

cirrhosis. Many factors have been proposed to

explain the increased incidence of gall stones

in cirrhosis. The main factor affecting gall

stone prevalence was severity of liver disease,

this could merely reflect the duration of

underlying chronic liver disease but could

also be a consequence of reduced hepatic

synthesis and transport of bile salts and

unconjugated bilirubin, and of high estrogen

levels (22) . High oestrogen levels may impair

gallbladder motility during pregnancy, so

Fornari F et al,(23) suggested that increased

levels of oestrogen and progesterone cause

gallbladder stasis amongst these patients

similar to pregnant women. By comparing the

results of the ejection fraction and the

distribution of gallbladder disease in the four

groups, it was noted that there was a negative

correlation between the two measures, the

higher the ejection fraction the lower the

incidence of gallbladder disease. In patients

with pure schistosomal periportal fibrosis, in

comparison with the mean ejection fraction in

the control group, it was clear that the ejection

fraction in patients with pure schistosomal

periportal fibrosis was significantly lower

than that of the control group. Also the

ejection fraction in patients with pure

schistosomal periportal was significantly

higher than that of group I & significantly

higher than that of group II, III. These results

were in accordance with to El-Masri and

Gumaa (24) who found that the bile of patients

with hepatic shistosomiasis contained more

cholesterol and less phospholipid than that of

patients with cholelithiasis. As regard the

mean serum estradiol it was clear that the

mean serum estradiol in chronic hepatitis c

patients with cirrhosis was significantly

higher than that of the control group, and also

significantly higher than that of group I, III.

In group III (patients with gallbladder disease

without HCV) it was found that the mean

serum estradiol was higher than that of the

control group, while the mean serum estradiol

in group III (patients with pure schistosomal

periportal fibrosis) was indifferent than the

control group. By comparing the results of the

mean ejection fraction and the mean serum

estradiol of all patients, it was found that there

was a negative correlation between the two

measures, the higher the serum estradiol the

lower the ejection fraction. Results of estra-

diol were in accordance with Fornari F et

al,(23) who suggested that increased levels of

oestrogen and progesterone cause gallbladder

stasis in cirrhotic patients similar to pregnant

women. And also came to agree with Everson

et al(24) as they found that high circulating

levels of estrogens may cause impaired

gallbladder motility during pregnancy. As

regards serum cholesterol, it has been noted

that mean serum cholesterol was significantly

higher in group III than the control group, and

the mean serum cholesterol in group II was

significantly lower than that of group III.

These results were in accordance with

Olokoba et al(25) who found that the mean

serum levels of cholesterol and triglycerides

were consistently higher in patients with

gallstones than in those without gallstones,

although the differences were of no statistical

significance. Chen et al.(26, 27) also found a

posi-tive association between gallstone

disease and decreased HDL cholesterol levels.

Increased serum level of cholesterol in

patients with gallbladder disease without

HCV may denote that it was a risk factor for

gallstone formation in those patients, while

serum cholesterol level seems to have no role

as a risk factor for gallstone formation in

chronic HCV patients or in cirrhotic patients.

Conclusion

Among persons with HCV infection, the

prevalence of GBD is highest among those

with more severe liver disease. This study

demonstrates that schistosomiasis represents a

risk factor for gallbladder stones formation.

The findings of this study are important

because of the large number of persons in

Egypt with HCV infection and GBD. People

with chronic Hepatitis C are at a greater risk

for developing gallbladder disease; those

harboring this virus are strongly encouraged

to practice gallstone prevention.

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