Pegylated interferon and lamuvidine in the treatment of Egyptian patients with HBe Ag positive chronic hepatitis B infection: S.ferritin as a marker of improvement

In Egypt, treatment of chronic HBV is not extensively studied and there were no comparative studies between different treatments all together. Also, worldwide, few such studies were performed with little or no significant differences in achieving both end of treatment and sustained virological responses when comparing lamuvidine to the combination of interferon and lamuvidine. The aim of this work is to compare the three arms of treatment; pegylated interferon, lamuvidine and combination of both agents; of chronic HBV infection who are HBe Ag positive in our Egyptian patients. This study included 71 Egyptian patients with chronic HBe Ag positive HBV infection divided into three arms: Group I including 23 patients treated with lamuvidine 100mg once daily for one and half year, group II including 23 patients treated with pegylated interferon alfa 2b 1.5micro g/kg/week for one and half year and group III including 25 patients treated with both agents for one and half years also. All patients were subjected to clinical, biochemical, histological and virological evaluation before, during and for about one and half years after treatment. History of schistosomiasis, antischistosomal treatment, in addition to ultrasonographic features of thickened portal tracts and antischistosomal antibody positivity were taken as evidences of presence of associated schistosomiasis. Serum ferritin level was estimated before and after treatment. Hepatitis serologies including HBsAg, HBsAb, HBeAg, HBeAb, anti HBdgG, and anti HCV and anti-HDV were determined by an enzyme immunoassay. Serum HBV DNA quantification was determined by a real time polymerase chain reaction [PCR], with serum samples obtained at baseline, at the end of therapy and one and half year later. The YMDD [tyrosine, methionine, aspartate, and aspartate] motif was tested on the serum samples at the end of first year of therapy or after by line probe assay. In lamivudine group, 30.4% showed complete biochemical and virological response to therapy with the mean ALT level of 35.29 +/- 5.06u/dL and AST level of 30.00 +/- 2.52u/dE in responding patients in comparison to 121.81 +/- 28.23u/dL and AST level of 107.25 +/- 39.48u/dL in non-responding patients after treatment. After 24 months, YMDD mutants were found in five patients in this group [21.7%]. In pegylated IFN group, 47.8% showed complete biochemical and virological response to therapy with the mean ALT level of 29.82 +/- 5.72u/dl and AST level of 22.6413.53u/dl in responding patients in comparison to 122.65 +/- 40.50u/dL and AST level of 112.33 +/- 23.02u/dl in non-responding patients after treatment. No YMDD mutants were detected during or after treatment. In combination therapy group, 32% showed complete biochemical and virological response to therapy with the mean ALT level of 30.00 +/- 3.12u/dl and AST level of 23.75 +/- 2.55u/dl in responding patients in comparison to 110.33 +/- 22.74u/dL and AST level of 144.71 +/- 44.18u/dL in non-responding patients after treatment. YMDD mutants were detected in 3 patients after the end of treatment [12%]. HBsAg and HBeAg seroconversion were detected more in patients treated by pegylated interferon and combination therapy but not statistically significant. Serum ferritin showed significant elevation [p<0.01] in all patients before treatment, and after treatment there were significant reduction in its levels in all groups [p<0.01] when compared to normal, this reduction was significantly obvious in responding than non responding patients in all groups. The change in histological activity index [HAI score] is significantly prognostic for interferon than lamuvidine therapy [p=0.014]. Changes in [HAI score] in combination therapy group was obvious than lamuvidine group but didn't reach statistical significance. In this study, no significant differences in biochemical and virological response between the three arms of treatment. Thus, from the virological point of view, three types of therapy are similar and still far from the hope of treatment of HBV. However, the development of YMDD resistance with the use of lamuvidine is a major concern and if a new nucleoside analogue can be added to or replace this drug to delay the development of resistance, such medications would be the best for their safety, route of administration and cost. The more HBsAg and HBeAg seroconversion in patients treated by combination therapy and pegylated interferon than lamuvidine, in addition to the rare development of YMDD mutants and the significantly better histological response; puts pegylated interferon in front of lamuvidine in the treatment of this disease. However, still the seroconversion and viral response is far beyond the goal and the door is widely open for more trials and different combinations to get the best effect adding new drugs recently approved for such infection such as adefovir, enticavir and others. Also, the dynamic observation of serum ferritin levels in patients with chronic viral hepatitis B during treatment might be helpful for monitoring and predicting patients' responses to the therapy

Helicobacter pylori in Arabs; clinical aspects and related diseases in comparative study in three Arabian countries

Helicobacter pylori represents one of the most common infections worldwide. It has been established as an etiologic factor in the development of peptic ulcer disease and chronic gastritis; and associated firmly with development of gastric neoplasia, including gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. Several extra digestive pathologies have been linked to H. pylori infection including cardiovascular, cutaneous, autoimmune, esophageal and other diseases such as sideropenic anaemia, growth retardation, and extragastric MALT-lymphoma. The aim of this work is to evaluate the contribution of H. pylori infection to the uncommon; digestive and extra-digestive; manifestations of patients in GIT clinics in some Arabian countries. A total of 623 H. pylori positive patients from three Arabian countries including 225 Egyptian patients, 188 Kuwait patients and 210 Saudi patients were studied and evaluated for all the possible manifestations of this infection. Evaluation was done by history, medical examination, routine and specific laboratory investigations, endoscopic and histopathological diagnosis. Follow-up after eradication was done to evaluate the response and improvement of such manifestations. This study included 339 males and 274 females distributed in the three countries. Recurrent H. pylori infection was found in 10.9% of all patients and was significantly more common in Saudi patients and associated with significantly higher incidence of thyroid dysfunction and pancreatitis. Mouth ulcers, vertigo, diabetes, gastric polyps and low serum iron were significantly more common in Egyptian patients than other population. Constipation, history of atypical chest pain, pancreatitis, thyroid dysfunction and ALT elevation were significantly more common in Saudi patients than other populations. Presence of GERD and migraine were found significantly more common in both Saudi and Kuwaiti than Egyptian patients. Diabetes mellitus was one of the commonest associated manifestations in this study and was found in 16.5% of all patients. Duodenal ulcer was found significantly more common in younger age group. Autoimmune haemolytic anaemia was found the only disease associated with significantly higher Cag A positivity. Constipation was also common in this population [11.9% of all patients] and was directly correlated with the presence and severity of gastritis. Pancreatitis was directly correlated with history of past infection, gastric ulcer, GIT malignancy, gastric outlet obstruction, arthritis and skin rash. Low serum iron and hemoglobin were more significant in patients with peptic ulcer disease and GIT malignancy. After eradication of infection, marked improvement during follow-up was noticed in patients with skin rash [28/37], mouth ulcer [37/59], and constipation [51/73] while mild to moderate improvement was noticed in those with migraine [11/260] and vertigo [19/49]. Also, highly significant increase in serum iron and hemoglobin levels [p<0.001] was found in all patients after eradication of infection when analyzed altogether and as separate groups without iron supplementation. The most sensitive and specific diagnostic tests for H. pylori in this cohort was the microscopic examination, followed by rapid urease test; both depend on gastric biopsies. It is concluded from this study that H. pylori infection is present in most Arabian countries nearly with similar, but of somewhat variable extent, manifestations whether digestive or extradigestive. The associated extradigestive manifestations described cannot be attributed to H. pylori in all cases, but it is recommended to screen for this infection and eradicate it particularly if there are additional upper GIT complaints. The presence of GERD should not affect the decision of treatment of this infection. Finally, diagnosis and treatment of H. pylori might be considered in the workup in the management of diseases with autoimmune pathogenesis such as ITP, autoimmune haemolytic anaemia, skin diseases, thyroid dysfunction, diabetes mellitus, and others

Prognostic value of serum pepsinogen isoenzymes in H. pylor eradication and other treatment modalities on the course of congestive gastropathy

Portal hypertensive gastropathy [PRG] is a common finding in patients with liver cirrhosis. Reduced gastric mucosal defense caused by H pylon may account for the pathogenesis of GI lesions in liver cirrhosis. Pepsinogens are secreted by chief cells in the fundus and body, The ratio of pepsinogen isozymes I and II in serum has good correlation with presence of metaplastic atrophic gastritis Most of the studies showed no relationship between H. pylon infection and congestive gastropathy in Fiver cirrhosis. The aim of this work is to estimate the prognostic value of serum levels of pepsinogen isoenzymes I and II and their ratio in addition to investigate the role and the eradication of H. pylon in the treatment of portal hypertensive gastropathy in comparison with other suggested treatments such as Daflon, sucralfait, propranolol and verapamil. Our intimate aim is to find .a simple treatment; if possible, for such common gastro-intestinal disease. This study included 64 cirrhotic patients divided into three groups: Group I: included 21 patients with congestive gastropathy and H. pylon infection and were treated with eradication therapy for H. pylon. Group 11: included 20 patients without H. pylon infection and without history of injection sclerotherapy are treated with sucralfait and Daflon. Group III: 23 patients without H. pylon infection and with history of injection sclerotherapy are treated with propranolol and verapamil. Upper endoscopy and gastric biopsies for histopathology and H. pylon staining before and after treatment were done in all patients in addition to pepsinogen isoenzymes I and II, serology and other routine tests. The three types of therapy showed significant clinical improvement in these patients. Most of these patients are suffering from dyspeptic symptoms in the form of epigastric discomfort and pain after meals, flatulence and distension. This was more marked in patients with H pylon infection. Serum Pepsinogen I levels and PG I/lI ratio were significantly less in group I with H pylon infection than groups II and III [P<0.001]. There is substantial improvement after treatment in all patients that was most marked in patients of group I after eradication of H pylon. Serum Pepsinogen I levels and PG I/Il ratio in group I showed significant increase after eradication of H pylon [P<0.001]. PHG was improved significantly in all groups. Also, there were no differences in the response of PHG in the three groups. Comparison of the response of oesophageal varices to therapy between the three groups found that oesophageal varices improved significantly in group I in comparison to group II. It is concluded from this study that H pylon may aggravate this disease process as estimated by reduction of pepsinogen I level and PG I/lI ratio, and its eradication may be beneficial in patients with liver cirrhosis and portal hypertension, as estimated by normalization of pepsinogen level. Also, other treatment modalities were effective in decreasing the severity of this disease, which means that this disease process may be aggravated by other factors than H pylon

Role of inflammatory cytokines [TNF- alpha and IL-6] in evaluation of anemia in CRF patients

Anemia is an early sign of chronic renal failure [CRF]. It is nearly universal in all patients with CRF and is associated with worse outcome. In recent years, evidence has accumulated for the roles of inflammatory cytokines in the inhibition of erythropoiesis in CKD-related anemia. The aim of our study is to investigate serum levels of some anemia markers and to evaluate the role of inflammatory cytokines 1L6 and TNF-alpha in patients with chronic renal failure. Sixty patients diagnosed as chronic renal failure and subjected to haemodialysis for at least 2 years, besides, 20 healthy volunteers were selected for our study. All were subjected to full clinical examination and hematological and biochemical investigation. In addition to estimation of anemia markers [serum levels of iron, TIBC, ferritin, folic acid and vitamin B12] and estimation of serum levels of inflammatory cytokines [lL-6 and TNF-alpha]. There were significant reduction in blood Hb concentration and hematocrite value [p< 0.00 1]. There also were significant reduction in serum iron, folic acid and vitamin B12 [p<0.01] whereas there was significant elevation in ferritin and TIBC levels [p<0.01]. Inflammatory cytokines, IL-6 and TNF-alpha showed highly significant elevation [p<0.001] when compared to the reference group. There were strong direct correlation [p<0.01] between serum TNF-alpha and serum iron level, while there were indirect correlation [p<0.01] between serum TNF-alpha and both of TIBC and ferritin. We can conclude that anemia could be a risk factor for progression of chronic renal dysfunction to end-stage renal disease and inflammation is a predictable event in its pathophysiology due to inhibition of erythropoiesis and also anemia correlates with the level of serum inflammatory markers [IL-6 and, TNF-alpha]. Furthermore, partial correction of anemia in patients with ESRD and CKD improves physiologic and clinical parameters and quality of life. Ongoing studies are also recommended to investigate the use of anti-cytokine treatment as anti-[TNF-alpha] antibodies in treatment of erythropoietin resistant anemia

Prevalence of coeliac disease in adult patients with symptoms of irritable bowel syndrome: a pilot study

The aim of this work is to estimate the prevalence and the potential clinical consequences of coeliac disease testing in adult Arab patients with IBS, and estimating the efficacy of IgA and IgG anti-gliadin antibodies, anti endomysial antibodies [EMA] IgA and anti-TG2 [IgA and IgG] on diagnosing celiac disease. As few recent studies have found higher prevalence of coeliac disease among patients diagnosed as irritable bowel syndrome [IBS] than general population [3-11% vs. 0.2-0.6%]. Similar studies showed that coeliac disease is as common in Middle Eastern countries as in Europe; in both the general population and at-risk groups. This is a prospective pilot study including 320 Arab patients with features compatible with IBS as defined by Rome III criteria without any other co-morbidity. The age of patients ranged between18-70 years. All patients were subjected to good history taking, clinical examination, and some investigations if needed such as stool, urine, CBC, liver enzymes, kidney function tests, ECG, electrolytes, H pylori serology, upper and lower endoscopy when indicated. Those diagnosed as having persistent criteria of IBS were tested for coeliac disease by IgA and IgG anti-gliadin antibodies, anti endomysial antibodies [EMA] IgA and anti-TG2 [IgA and IgG]. Upper endoscopy and duodenal biopsies were done and gluten free diet was implemented for only those with positive serological test. The same tests were repeated after period of about 6 months. Anti-gliadin antibodies were found positive in 15/320[4.69%] patients [14 with IgA and 13 IgG], EMA IgA in 13/320 [4.06%], anti-TG2 IgA in 12/320 [3.76%] and anti- TG2 IgG in 13/320 [4.06%]. Abdominal pain, diarrhea, dyspepsia, postprandial distress, epigastric pain, distension and chronic diarrhea were significantly higher and more common in combinations in those with positive serology in comparison to serologically negative patients [P < 0.05]. Haemoglobin level, serum iron, albumin and calcium were found to be significantly lower in those with positive serology in comparison to serologically negative patients [P < 0.05]. All these parameters improved significantly after gluten free died [GFD] for about 6 months [P< 0.05]. Only 11 patients [74.44% of those with positive serology and 3.49% of total patients] were diagnosed by biopsies as compatible with coeliac disease of which, two patients have family history of coeliac disease in first degree relatives. After gluten free died [GFD] for about 6 months, seroconversion to negative tests occurred in 6 patients for AGA-IgA, 4 for AGA- IgG, 3 for EMA IgA, 5 for Anti-TG2 IgA and 5 for Anti-TG2 IgG. Also, the grade of histopathology showed complete healing in 4 patients and improvement to lower grades in 4 patients after GFD. Worsening occurred in one case and still 7 cases showed the same grade of the disease. It is concluded from this study that minimally symptomatic coeliac disease can easily be mistaken for IBS. The presence of many persistent gastrointestinal symptoms in addition to the lower serum levels of some nutritional parameters must alert the physicians to screen for coeliac disease. The efficacy of IgA and IgG anti-gliadin antibodies, anti endomysial antibodies [EMA] IgA and anti-TG2 [IgA and IgG] were nearly the same. So any serological test can be used for the screening, especially EMA TG2 as they are easier and cheap. But this must be confirmed by tissue diagnosis which is the gold standard for diagnosis. Finally, screening for coeliac disease among patients with IBS must be considered to offer better prognosis to those patients simply by gluten free diet

Role of cytokines [IL1-beta, IL2, IL6 and IL8] in some extrahepatic manifestations of chronic HCV patients, Sjogren syndrome

Several extrahepatic diseases have been associated with chronic HCV infection. Cytokines are peptides produced by the cells and play an important role in the defence against viral infections. The aim of our research is to investigate serum level of cytokines [IL1-beta, IL2, IL6 and IL8] in chronic HCV infected patients and find out the prevalence of primary Sjogren Syndrome [SS] and the relationship between disease severity and serum levels of these cytokines. This study included 60 patients [34 males and 26 females] with chronic virus C hepatitis, with mean age of 45 +/- 10.2 years and 20 healthy subjects [12 males and 8 females] with mean age 47 +/- 8.5 years as a control group. Biochemical assessment of hepatic condition and viral markers for hepatitis C virus [anti-HCV] and hepatitis B virus [HBs Ag and anti-HBc Ab], and serum levels of cytokines [IL1-beta, IL2, IL6 and IL8] were conducted to all patients. According to modified Child's criteria, the degree of liver affection was assessed for patients with chronic hepatitis. Liver biopsy was performed to confirm chronic liver hepatitis. Patients diagnosed having Sjogren Syndrome [SS] would further subjected to chest and hand X-ray, thyroid function tests and immunological study [anti-Ro, anti-La antibodies and Rhematoid factor]. There was highly significant elevation [p<0.0l] of interleukins 1, 2, 6 and 8, and ALT between patient and control groups. There were positive correlation between serum cytokines levels [IL1-beta, IL2, IL6] and liver function test ALT [p<0.05] and strong positive correlation between IL8 and ALT [p<0.0l]. Ten of sixty patients [16.6%] were diagnosed of having SS, 60% were males with mean age of 48 +/- 4.5 years. A highly significant direct correlation was found as regards number of swollen joints, duration of morning stiffness and serum levels of cytokines [IL1- beta, IL-2, 6 and IL-8]. High liters of anti Ro and anti La antibodies were associated with higher levels of interleukin 6. Eight patients showed evidence of hypothyroidism and four patients showed evidence of peripheral neuropathy. Cytokines and free radicals are thought to be responsible for the pathologic changes, but the precise mechanisms are not clear. The significant correlations between the severity of different clinical and laboratory parameters of SS and serum levels of cytokines can be explained by the assumption that proinflammatory cytokines inhibit neurally mediated lacrimal gland secretion as well as, in glandular epithelial cells the local production of cytokines by both mononuclear and epithelial cells may be involved in the immune-mediated destruction of exocrine glands in patients with primary SS. It is concluded that in chronic hepatitis C infection there is significant elevation of serum cytokines [IL1-beta, IL2, IL6 and IL8], and there is high prevalence rate of primary Sjogren Syndrome, specially in males of old age. The severity of SS clinical picture and laboratory diagnostic markers is directly correlated to the serum levels of those cytokines