CCR1 and CCR5 expressions on peripheral blood mononuclear cells from patients with liver cirrhosis and hepatocelluar carcinoma

Chemokine receptors [CCR1 and CCR5], have been implicated in hepatic inflammation and hepatocellular carcinoma [HCC]. The present study aimed to investigate the expressions of CCR1, CCR5 on peripheral blood mononuclear cells [PBMCs] of Egyptian patients with liver cirrhosis [LC] and HCC and their correlation to the severity of liver disease and the clinical features of HCC. Isolated PBMCs from 25 patients with HCC, 10 LC patients and 9 adult healthy controls were stained with monoclonal antibodies against CD4, CD8, CCR1 and CCR5, then detected by using a flow cytometry technique. Patients were diagnosed by abdominal ultrasound [US] and computed tomography [CT] scan findings, biochemical liver function tests, serum alpha-fetoprotein [AFP]. Our data revealed that CCR1 and CCR5 expressions in liver cirrhosis patients were significantly higher than healthy controls [P=0.008 and 0.053 respectively], as well as in HCC patients but the increment were not significant [P= 0.120 and 0.216 respectively]. The expressions of CCR1 and CCR5 were increased in liver cirrhosis than in HCC patients, but the increment were not significant [P=0.120 and 0.216 respectively]. However, both CCR1 and CCR5 were decreased with increasing number of liver tumor in a negative linear regression correlation. Patients with liver cirrhosis or HCC showed lower CD4 and CD8 T cells count compared with healthy controls. In Conclusion The up-regulations of CCR1 and CCR5 in patients with hepatic cirrhosis confirmed the activation of the CC chemokine system in human fibrogenesis and may play a role in recruitment of lymphocytes to the injured liver

Immunohistological examination of long term changes of the t-cell mediated immune response in egyptian patients with chronic hepatitis C with and without schistosoma mansoni infection

The host immune response is playing a key role in liver injury occurring in patients with chronic hepatitis C or schistosomiasis or in case of coinfection. The rational of the current study is to investigate the cell mediated immunity in the liver of patients with or without cirrhosis due to hepatitis C or schistosomiasis or both. The CD3 [Tlymphocytes], CD4 [helper/inducer T-cells], CD8 [suppressor/cytotoxic T-cells], CD11b, and CD16 [NK activity] were counted immunohistochemically in liver samples using specific monoclones in four patient groups, non-cirrhotic patients free of schistosomiasis with hepatitis C [Group I], non- cirrhotic patients coinfected with schistosomiasis and hepatitis C [Group II], cirrhotic patients free of schistosomiasis with hepatitis C [Group III], and cirrhotic patients coinfected with both schistosomiasis and hepatitis C [Group IV]. The results showed that there is a significant difference between the four groups of patients regarding CD4 count. Patients without schistosoma coinfection and without cirrhosis [Group I] showed significantly [P < 0.001] risen counts of CD4+ compared to patients with coinfection and cirrhotic remodelling [Group IV]. For patients suffering from liver cirrhosis [Group III] significantly elevated levels of CD4+ lymphocytes [P = 0.014] were detectable compared to patients already suffering from liver cirrhosis and coinfection [Group IV]. The counted CD4 cells in chronic hepatitis C group without S. mansoni infection [group one] was found elevated versus the count of CD4 cells in the group with the coinfection [group two] and this was statistically significant [P = 0.01]. The CD8 count was statistically highly significant between the four groups. CD8 cells count in the two groups with the coinfection was found elevated against the other two groups with HCV infection only. On the other hand, the patients coinfected with schistosome without cirrhosis [Group II] and with cirrhosis [Group IV] showed a significant elevation of CD8 versus patients infected with HCV only without cirrhosis [Group I] [P = 0.001] and [P < 0.0001] respectively. Moreover, the patients coinfected with schistosome with cirrhosis [Group IV] showed a significant elevation of CD8 versus patients infected with HCV only with cirrhosis [Group III] [P = 0.022]. The obtained CD4/8 ratio was decreased in coinfected versus the nonconifected patients. The CD3, CD11b, and CD16 cells counts were non-significantly different among the four groups. Collectively, the schistosome coinfection increases the level of CD8 and decreases the CD4 count in livers of cirrhotic and non-cirrhotic patients. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes cells may play a role in the immunopathogenesis of liver cirrhosis in patients with HCV and severely in coinfected patients with both hepatitis C and schistosomiasis

Copro-antigen detection versus direct methods for the diagnosis of Giardia Lamblia in patients from the national liver institute

In this study a commercially available immunoenzymatic assay to detect G. lamblia specific copro-antigen was evaluated. A total of 90 stool samples were tested. Diagnosis of giardiasis by ELISA for copro-Ag detection was positive in 46 [51.1%] patients whereas by direct stool analysis after formol ether concentration G. lamblia was detected in 38 [42.2%] patients only. ELISA technique for detection of Giardia copro-antigen had a sensitivity of 97.3% and a specificity of 82.6% with PPV of 80.4% and a NPV of 97.7%

Angiotensin converting enzyme-2 and transforming growth factor beta-1 are over-expressed during fibrogenesis in liver tissue of patients with chronic hepatitis C virus infection

Hepatitis C virus [HCV] infection leads to chronic hepatitis which may eventually progress to cirrhosis and hepatocellular carcinoma. A significant relationship between inheritance of hightened expression of angiotensin II [A-2] and transforming growth factor beta [TGF-beta] and the development of progressive hepatic fibrosis has been noted. Recent studies have revealed that the renin angiotensin system [RAS] and the local RAS components are implicated in liver fibrogenesis and carcinogenesis. TGF-beta1 is a key cytokine in inflammation that regulates the production and deposition of extracellular matrix, directly stimulates angiogenesis and plays an important role in tumorigenesis. In this study we aimed to investigate the expression of angiotensin converting enzyme-2 [ACE-2] and TGF-beta1 in liver biopsies from patients with HCV infection alone or with hepatocellular carcinoma [HCC] on top of HCV cirrhosis. Liver biopsies from 40 patients with HCV infection and 20 patients with HCC on top of HCV-cirrhosis were included in this study. Semiquantitative immunohistochemical analyses were performed using ACE-2 and TGF-beta1 antibodies on paraffin embedded liver sections. Immunohistochemical results revealed that the immunoreactive score of ACE-2 and TGF-beta1 correlated significantly with the stage of fibrosis [p=0.05, p=0.001 respectively] and that TGF-beta1 correlated also with the histological activity index [p=0.05]. Liver tissue from HCC demonstrated enhanced and differential expression of both ACE-2 and TGF-beta1. Our data provide evidence for the implication of ACE.-2 and TGF-beta1 in liver fibrogenesis and carcinogenesis; a finding that might be of prognostic and therapeutic value

Value of screening colonoscopy in the diagnosis of Egyptian patients with lower gastrointestinal symptoms

Colorectal cancer is a major cause of mortality allover the world. Fecal occult blood testing, flexible sigmoidoscopy and total colonoscopy are the most commonly recommended screening tests for colorectal cancer, yet screening rates are still below target levels. To fully realize the benefits of early detection of colorectal cancer, screening rates must be improved. The current study has been conducted to study the current pattern of colorectal lesions from endoscopic and histopathologic perspectives in relation to clinical and laboratory aspects in Egyptian patients with different lower gastrointestinal symptoms. 165 cases with different lower gastrointestinal symptoms presented to Gastroenterology and Endoscopy Unit, Specialized Medical Hospital, Mansoura University. Clinical, laboratory, colonoscopic and histopathological examination of colonoscopic samples were done during the period from October 2005 to July 2006. The main lower gastrointestinal symptoms were abdominal pain, distension, altered bowel habits, dysentery and rectal bleeding. Ulcerative colitis represented 9.1% while colorectal carcinoma represented 4.1% of cases. The commonest symptoms and laboratory findings associated with colorectal carcinoma group were constitutional symptoms, constipation, rectal bleeding, fecal occult blood and iron-deficiency anemia. The colonoscopic examination is safe, accurate and cost-effective means of the screening for colorectal carcinoma

diagnostic value of serum and bile cyfra 21-1, CEA and CA 19-9 in cases of cholangiocarcinoma

The aim of the present study was to assess the diagnostic value of Cyfra 21-1, CA 19-9 and CEA in serum and bile of patients with CCA. The present study was conducted on 20 patients with cholangiocarcinoma [CCA group] diagnosed on clinical and pathological grounds, in addition to 20 cases with benign cholestatic disorder and 20 matched healthy subjects as a control group. Cyfra 2 1-1, CEA and CA 19-9 were measured in serum and bile of patients and in serum of controls. Serum CEA, CA 19-9 and Cyfra 21-1 concentrations were significantly higher in patients with cholangiocarcinoma than patients with benign cholestatic disorder and controls. Moreover, the mean bile .concentrations of CEA, CA 19-9 and Cyfra 21-1 were significantly higher than serum concentrations. The sensitivity, specificity and diagnostic accuracy of serum and bile Cyfra 21-1 were significantly higher than those obtained using either CEA or CA 19-9. The serum and bile concentrations of CEA, CA 19-9 and Cyfra 21-1 were significantly higher in late stages of CCA in comparison to early stages. The addition of tumor markers CEA, CA l9-9 and Cyfra 21-1 to brush cytology increases its sensitivity in diagnosis of cholangiocarcinoma from 44% up to 84%. CEA, CA 19-9 and Cyfra 21-1 measurements in bile are important for the supplementary diagnosis of cholangiocarcinoma. Cyfra 21-1 is a superior tumor marker than CEA in diagnosis cholangiocarcinoma. Combining brush cytology with CEA, CA 19-9 and Cyfra 21-1 can raise the diagnostic yield

Serum matrix metalloproteinase-9 and tissue inhibitor of 3tetalloproteinase-1 in Egyptian patients with chronic liver disease: correlation with liver fibrosis

Chronic liver disease of different etiologies leads to cirrhosis. The main pathological mechanism of progression to cirrhosis is fibro genesis. Recognition of liver fibrosis or cirrhosis is difficult without liver biopsy. There is an urgent demand for a noninvasive reliable serum marker for liver fibrosis. Alterations in circulating matrix metalloproteinase-9 [MMPs] and tissue inhibitor of metalloproteinase-1 [TIMPs] concentrations and their correlation to the inflammatory activity and the histological changes are fairly well established, thus, the rationale of the present study was to evaluate the relationship between serum MMP-9, and TIMP-1 to liver status in patients with chronic liver disease. This study included 50 patients with chronic liver disease, 18 patients with chronic hepatitis, 22 patients with liver cirrhosis and 10 patients with hepatocellular carcinoma [HCC]. Twenty matched age and sex healthy volunteers were enrolled as control group. The obtained data showed that the lowest serum level of MMP-9 was found in chronic hepatitis patients compared to the control [P<0.05]. The MMP-9 serum level decreased during progression of chronic hepatitis to cirrhosis showing the least level in cirrhotic group. The serum TIMP-1 level was significantly higher in cirrhotic group compared to chronic hepatitis [P<0.05] and control [P<0.001] groups. Serum MMP-9 was negatively correlated to both the TIMP-1 level and to the histological severity of chronic hepatitis. There was a positive correlation between serum TIMP-1 and degree of fibrosis [r= 0.73, P< 0.001]. There were a statistically significant increase of MMP-9 [Pc0.001] and TIMP-l [P

Serum and biliary cytokeratin fragment CYFRA 21-1, as a marker of resectability for extrahepatic cholangiocarcinoma

Serum levels of CEA and CA 19.9 are occasionally elevated in cases of cholangiocarcinoma [CC]. They, however, have low sensitivity and specificity, which makes the diagnosis of CC difficult, and better tumor markers are needed. CYFRA 21-1, a cytokeratin fragment, is being evaluated as a tumor marker with diagnostic potential for small cell lung carcinoma. The resectability of CC is difficult to assess accurately pre-operatively using available laboratory and imaging techniques. The aim of the present study was to assess the diagnostic value of CYFRA 21-1, CA 19.9, and CEA in serum and bile of patients with extrahepatic CC. and to evaluate whether any of these markers can be used to assess resectabilily. Fifty patients with extrahepatic obstructive jaundice were included in this study. Group 1: 30 patients with histologically proven CC had serum and bile samples measured for CYFRA 21-1, CA 19.9; and CEA. Group II: 20 patients with calcular obstructive jaundice had serum and bile samples obtained during endoscopic removal of stones to control for the effect of biliary obstruction on CYFRA 21-1, CA 19.9, and CEA. Sixteen patients in whom imaging studies showed resectability were explored and operative findings were correlated to tumor markers. CEA and CA 19.9 were measured using enzyme immnunoassay [EIA,], and CYFRA 21-1 level was measured using electrochemiluminescence immunoassay [ECLIA] in serum and bile of the CC patients and the caicular obstructive jaundice controls. Patients with CC had significantly higher serum levels of CEA [24.5 +/- 6 vs 4 +/- 1.3 ng/ml. p<0.01] CA 19.9 [118.9 +/- 25.4 vs 31.2 +/- 8.4 U/ml, p< 0.01] and CYFRA 21-1 [8.3 +/- 2.7 vs 2.1 +/- 0.5 ng/ml, p<0.01] than patients with benign calcular cholestatic disorder, and bile concentration of the 3 markers was sign higher than serum concentrations. Among the 16 patients who underwent surgery, serum and biliary levels of CYFRA 21-1 were significantly higher with irresectable tumors. CYFRA 21-1 may be a useful marker for resectabilily saving many unnecessary operations. This, however, needs further larger studies to be documented

effect of stent placement on the size of common bile duct stones in cirrhotic patients: a prospective study

Background: Endoscopic retrograde cholangio-pancreato-graphy [ERCP], endoscopic sphincterotomy [ES] and basket extraction are currently used to remove bile duct stones. The technical difficulty of stone extraction increases with size of stone. Apart from surgical removal, biliary stenting is an alternative for treating difficult cases

Aim: To compare the sizes of the stones before and after stenting in cirrhotic patients with irretrievable common bile duct stones

Patients and methods: Twenty five patients with difficult common bile duct stones were treated by endoscopic stenting. They were 15 males, 10 females with mean age of 57.9+/-9.5 years, 7 of them were Child class A, 12 Child B and 6 Child C. Patients were followed-up at 3 months intervals

Results: Twenty patients [80 %] had a reduction of stone size, 3 had no change and in 2 patients it became slightly larger in size but not in number. Before stenting, the -diameter of stones ranged from 2.3 mm to 33 .mm [mean 22.9+/-3.7 mm]. After stenting, the size ranged from 1.3 to 30mm [mean 15.5+/-4.1 mm]. The difference in the stone diameter was statistically significant, P < 0.0001. Stones were successfully extracted in 22 patients [88%] after stenting, following 2. 2+/-0.4 endoscopic procedures [range 2-3]

Conclusion: Biliary stenting is a safe and effective mode of treatment of common bile duct stones in patients where stone extraction has failed after endoscopic papillotomy. These stones became smaller after stenting. As the difficulty of stone extraction increases with stone size, a period of stenting may make subsequent removal easier for patients with large stones

Some immunological studies and HLA-DRB1 in hepatitis C virus-related necrolytic acral erythema

Necrolytic acral erythema [NAE] is unique in its acral location and strong association with hepatitis C virus [HCV] and altered immunological junctions. The aim of the present work was to evaluate HLA DRB1 alleles and association of some parameter of immune system functions [complements C3 and C4, antismooth muscle antibody [ASMA] and antinuclear antibody [ANA] in NAE. Response of cutaneous lesion to low dose interferon alpha [3 million unit [MU] / week] and hydroxychloroquine was also evaluated. This study included 22 patients with HCV- related NAE [group I], 45 chronic hepatitis C without NAE [group II as pathological controls] and 45 healthy subjects [group III, normal controls]. ANA was positive more in patients than normal controls [18.2% vs 0%, P <0.003], however no significant difference was seen between patients groups. ASMA was positive significantly more in patients with NAE than HCV patients, and in both patients groups than normal controls 59.1%, 17.3% and 0%; P<0.001 and 0.0001 respectively]. A significant decrease in C3 and C4 was found in NAE patients than HCV patients without NAE, [P<0.01] and in both patients groups than normal controls [P<0.001]. NAE was associated with HLA -DRB1 03, [77.7%, 16 of 22 vs 24.2%, 11 of 45 of normal controls, Pc <0.0009 and 35.6% 16 of 45 HCV patients without NAE, Pc=0.03. Clinical improvement and significant decrease in ALT [P<0.001] was observed in NAE patients after two months of interferon alpha and hydroxychloroquine therapy. Necrolytic acral erythema [NAE] appears to be an immune mediated response in chronic HCV patients, associated with, lower C3 and C4 and higher frequency of positive ASMA. The results suggest that the development of HCV related ANE is associated with HLA-DRB1 03 marker. And low dose interferon alpha [3 MU per week] and hydroxychloroquine are good treatment modalities for NAE

Decreased Helicobacter pylori-associated gastric epithelial proliferation by concurrent Schistosomal infection

Helicobacter pylori [H. pylori] injection is associated with increased gastric epithelial proliferation, the enhanced epithelial proliferation is important in developing gastric carcinoma. Some developing countries with a high prevalence of H. pylori infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by T-helper cell, type 1 [Th1] response may be modulated by concurrent parasitic infection. Pathogenic helminths of the genus Schistosoma cause T-helper cell, type 2 [Th2] response to parasite eggs. The Th2 response is usually associated with down regulation of Th1 cytokine synthesis. The aim of the present study was to assess whether concurrent Schistosoma mansoni infection with H. pylori has an effect on gastric mucosal injury in view of cell proliferation, apoptosis, pathological changes, nitric oxide and oxyradicals status. Between April 2001 and March 2002, 73 patients [13 child and 60 adults] were subjected to upper gastrointestinal endoscopy for dyspepsia and liver cirrhosis in the National Liver Institute, Menoufiya University. Four biopsy specimens were taken, two from the greater curvature of the antrum and two from the upper body of the stomach, biopsies were obtained from any lesion as well as from apparently healthy mucosa. One snap from each site was preserved in RNA later solution, then kept at -80°C till utilized for estimation of DNA-flow cytometric assay, reduced glutathion [GSH], catalase [CAT], superoxide dismutase [SOD], Nitric oxide [NO], and lipid peroxidation product- malondialdehyde [MDA]-. Diagnosis of bilharziasis was done by stool analysis, or by sigmoidoscopy and rectal snip. OF the 73 patients, 60 patients were cirrhotic [20 Child A, 34 B, 6 C], 48 were H. pylori-positive and 25 H. pylori negative. The mean age in H. pylori positive patients [46.31 +/- 10.7 years] was significantly less than in H. pylori - negative patients [52.8 +/- 7.2 years]. Infection with H. pylori alone correlated with increased DNA s-phase, proliferation activity and apoptosis [sub-G phase] [p 0.04, 0.03 and 0.04] respectively. Concurrent infection with schistosomiasis occurred in 34 patients and it significantly suppressed DNA 5-phase [P=0.001], proliferation activity [p<0.004], and apoptosis [sub-G phase], [p>0.05]. On contrast, concurrent infection had an adverse effect on liver cirrhosis with increased incidence of upper gastrointestinal bleeding. Schistosomal concurrent infection with H. pylori is associated with higher incidence of superficial gastritis, and may complicate liver cirrhosis with increased upper gastrointestinal bleeding. On the other hand, concurrent schistosomal infection may have a protective effect against the possible progression of H. pylori induced gastritis towards gastric carcinoma, by modulating the cytokine profile of the gastric mucosa with suppression of the proliferation activity. A detailed study of the cytokine expression in similar cases is recommended for unraveling the mystery of this phenomenon

Mesenteric vein thrombosis: a diagnostic and therapeutic challenge

Mesenteric vein thrombosis [MVT] is a rare but a potentially lethal form of mesenteric ischemia. Thirteen patients having MVT [7 males and 6 females] were included in this study. Their ages ranged from 30 to 50 years with a mean +/- standard deviation [SD] of [46.15 +/- 5.52]. Nine of these patients [9/13; 69%] had associated hepatopancreatic diseases: 4 with hepatocellular carcinoma [HCC] on top of cirrhosis, 3 with cirrhosis and previous splenectomy, one with cirrhosis, and one with pancreatitis. The remaining four patients [4/13; 31%] had associated nonhepatopancreatic disease: 2 with deep venous thrombosis [DVT], and 2 with history of contraceptive pill intake. Severe subcontinuous abdominal pain out of proportion to the physical findings [11/13; 84%] and abdominal distention [9/13; 69%] were the major symptoms. Color duplex ultrasound [US] was performed in all patients and was diagnostic for MVT in only 10 patients [10/13; 77%]. In the remaining 3 patients, diagnosis of MVT was established by computed tomography [CT] in 2, and mesenteric angiography in one. Once the diagnosis of acute MVT was confirmed, all patients were anticoagulated with heparin.Signs of peritonitis were the main indication for immediate exploratory laparotomy in the studied cases [8/13; 61.5%]. Minimal small bowel resection with primary anastomosis was performed in 5 patients, minimal small bowel resection with diverting ileostomy in one, extended small bowel resection with primary anastomosis in one, and laparotomy without resection in one. The determination of viability in the marginally perfused bowel was done with clinical assessment. For further evaluation of bowel viability in borderline cases, Doppler US was performed in 4 patients. The 30-day operative mortality was reported in three patients [3/8; 37.5%]. All of them were having liver cirrhosis that was associated with malignancy in one and splenectomy in another. The 30-day mortality in the five non-surgically treated patients was 60% [3/5] that was mostly due to advanced liver malignancy. In conclusion; a high index of suspicion and recognition of high risk factors coupled with a history of non-specific abdominal symptoms should alert clinicians to the possibility of MVT. Early diagnosis using color duplex US or CT and prompt anticoagulation are the mainstay of therapy unless there are signs of peritonitis that necessitate surgical resection of the infarcted bowel. Although a primary anastomosis can be accomplished in most situations, a diverting ileostomy may often be the prudent approach in cases with poor liver function and bad general conditions. During operation, all nonviable bowels should be resected with intent for a second-look laparotomy after 24 hours if there is any question of ongoing ischemia. We recommend using intraoperative Doppler US for detection of the arterial signals in evaluation of the marginally viable bowel