Usefulness of Serum Pepsinogen I as a Biomarker in Early Diagnosis of Aetiology of Dyspepsia.

BACKGROUND: Dyspepsia, according to Rome III criteria, is defined as pain or discomfort centred in the upper abdomen in addition to symptoms like early satiety, postprandial fullness, bloating and nausea. Pepsinogens which are secreted by chief cells of the stomach play an important role in its physiology. They could determine the functional state of the mucosa in health and in diseased conditions. Serum levels of pepsinogen have aided the diagnosis of gastric pathologies such as atrophic gastritis, peptic ulcer disease and gastric cancer. Pepsinogen assay, being a simple, non-invasive procedure, can aid in determining the aetiology of dyspepsia especially in a resource poor setting. OBJECTIVE: This was to evaluate the diagnostic significance of serum pepsinogen I in patients with dyspepsia. METHODS: The study involved 112 adult patients with dyspepsia and an equal number of controls. A questionnaire was used to obtain biodata, clinical features and other relevant information. The patients had abdominal ultrasound scan, urea breath test and upper gastrointestinal endoscopy (UGIE), while the controls had only abdominal ultrasound scan. Sera prepared from 10ml of venous blood from each participant were stored at -20ºC and later analysed for pepsinogen I (PG I). RESULTS: Females predominated in both groups (F:M = 1.4:1). The mean age of cases was 51±15.9 years and was similar to that of controls 51.4±16.5. The most frequent symptom was epigastric pain in 101 (90.2%) patients. Median pepsinogen I level in patients (28.5ng/ml) was significantly lower than in controls (68.8ng/ml) (p<0.001). The most frequent endoscopic finding was gastritis. Serum PG I level at a cut-off point of 79.5ng/ml had a specificity of 88.8% and sensitivity of 40% in identifying dysplasia. CONCLUSION: Serum PG I level was lower in patients with dyspepsia than controls. It showed high specificity in identifying dysplasia and could be a biomarker for early gastric cancer.

CONTEXTE: La dyspepsie, selon les critères de Rome III, est définie comme une douleur ou une gêne centrée sur la partie supérieure de l'abdomen, en plus de symptômes tels qu'une satiété précoce, une plénitude postprandiale, des ballonnements et des nausées. Les pepsinogènes, sécrétés par les cellules principales de l'estomac, jouent un rôle important dans sa physiologie. Ils peuvent déterminer l'état fonctionnel de la muqueuse, qu'elle soit saine ou malade. Les taux sériques de pepsinogène ont facilité le diagnostic de pathologies gastriques telles que la gastrite atrophique, l'ulcère gastroduodénal et le cancer gastrique. Le dosage du pepsinogène, qui est une procédure simple et non invasive, peut aider à déterminer l'étiologie de la dyspepsie, en particulier dans un contexte de ressources limitées. OBJECTIF: Évaluer l'importance diagnostique du pepsinogène I sérique chez les patients souffrant de dyspepsie. MÉTHODES: L'étude a porté sur 112 patients adultes souffrant de dyspepsie : L'étude a porté sur 112 patients adultes souffrant de dyspepsie et un nombre égal de témoins. Un questionnaire a été utilisé pour obtenir les données biologiques, les caractéristiques cliniques et d'autres informations pertinentes. Les patients ont subi une échographie abdominale, un test respiratoire à l'urée et une endoscopie gastro-intestinale supérieure, tandis que les témoins n'ont subi qu'une échographie abdominale. Les sérums préparés à partir de 10 ml de sang veineux de chaque participant ont été conservés à -20ºC et analysés ultérieurement pour le pepsinogène I (PG I). RÉSULTATS: Les femmes prédominaient dans les deux groupes (F:M = 1,4:1). L'âge moyen des cas était de 51±15.9 ans et était similaire à celui des témoins 51.4±16.5. Le symptôme le plus fréquent était la douleur épigastrique chez 101 (90,2 %) patients. Le taux médian de pepsinogène I chez les patients (28,5 ng/ml) était significativement plus bas que chez les témoins (68,8 ng/ml) (p<0,001). Le résultat endoscopique le plus fréquent était la gastrite. Le taux sérique de PG I à un seuil de 79,5 ng/ml avait une spécificité de 88,8 % et une sensibilité de 40 % dans l'identification de la dysplasie. CONCLUSION: Le taux de PG I sérique était plus faible chez les patients souffrant de dyspepsie que chez les témoins. Il a montré une spécificité élevée dans l'identification de la dysplasie et pourrait être un biomarqueur pour le cancer gastrique précoce. Mots-clés: Dyspepsie, Pepsinogène I sérique, Helicobacter pylori, Biomarqueur.

Role of lamivudine in the therapy of Nigerian patients with Chronic HBV infection.

AIMS AND OBJECTIVES: The study was conducted to determine the role of lamivudine in the treatment of Nigerian patients with chronic HBV infection (CHB). MATERIALS AND METHODS: Twenty one Nigerian patients with laboratory, histologic and clinical features of CHB were studied over a period of 30 months for response to a six-month therapy with lamivudine using liver biopsy as gold standard for assessment of response to therapy. RESULTS: The mean age of the patients was 32.6±9.3 years and the receipt of injection from chemists (76%) was the most common risk factor for HBV infection among the subjects. About 67% of the patients were asymptomatic while 90.5% had normal liver span. Patients with low serum albumin, raised serum alkaline phosphatase, bilirubin and globulin prior to lamivudine therapy had restoration to normal values after 24 weeks of therapy. There was prolongation of prothrombin time (five patients) and hypokalaemia (one patient) after lamivudine therapy but there were no changes in the HBsAg, anti-HIV and anti-HCV status of all the patients. Although, post therapy liver biopsy was declined by 8 patients and contraindicated in 5 patients, there was 48% reduction in Knodell score of histologic findings in the liver biopsy specimens of 8 patients who had pre- and post-lamivudine therapy liver biopsies. CONCLUSION: The findings from this study suggested that six-month therapy with lamivudine is beneficial in treating Nigerian patients with CHB using biochemical markers and liver histology in assessing response to treatment.

Hepatitis B virus DNA in patients with HBsAg in south western Nigeria.

There are about 400 million people with chronic hepatitis B virus (HBV) infection worldwide with a potential of adverse sequelae including hepatocellular carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of an infected person probably reflects more accurately the replicative activity of the virus and therefore may serve as a better maker for management of the infection. This study was designed to determine the rate of detection of HBV DNA in blood samples of patients with HBsAg positive in Nigeria in comparison with the HBe and anti-HBe used widely as serological markers of infectivity. Plasma samples from 105 patients with HBsAg positive were tested for the presence of HBeAg and anti-HBe using a commercial enzyme-linked immunosorbent assay while plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the 105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti-HBe, respectively, while 8 (7.6%) were negative for both HBeAg and anti-HBe. HBV DNA was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%) were positive for HBeAg and anti-HBe, respectively. HBV DNA was detected in 78.4% of the HBeAg negative samples and in all the eight samples that were negative for both HBeAg and anti-HBe. The implication of these findings in the management of patients with HBV infection is compelling.

Characteristics of inflammatory bowel disease in three tertiary health centers in southern Nigeria.

BACKGROUND: Inflammatory bowel disease (IBD) refers to two chronic inflammatory disorders of the gastrointestinal tract which is generally believed to be rare in most African countries. The objectives of the current study were to present the experience of three tertiary gastroenterology centers in southern part of Nigeria on IBD, highlighting the age distribution of the patients seen, management and the impact on the quality of their life in university-based community-type practices in Nigeria. METHODS: This was a retrospective review of charts of inflammatory bowel disease seen between January 2007 and June 2010 at three teaching hospitals in Southern Nigeria. Diagnosis of IBD was made from clinical manifestations, colonoscopic and histopathological findings. RESULTS: During the study period, 12 patients presented with clinical features consistent with inflammatory bowel disease. There were 8 (66.7%) males and 4 (33.3%) females and had ages ranged from 18 years to 80 years with a median of 26.5 years. Eight (66.7%) patients had ulcerative colitis while 4(33.3%) had Crohn's disease. Ten (83.3%) patients had severe disease with main clinical features being recurrent diarrhoea and passage of mucoid bloody stools. All the patients had treatments with sulphasalazine or mesalazine, steroids and antibiotics with good responses. One patient died following the occurrence of toxic megacolon. CONCLUSION: Although IBD is uncommon in Nigeria, high index of suspicion is necessary by attending physicians managing patients with recurrent passage of mucoid bloody stools. Prompt gastroenterological referral and judicious use of colonoscopy and biopsy will assist in making the diagnosis.

Correlation of cag-A serological status with histological parameters of chronic gastritis among dyspeptic patients in south western Nigeria.

BACKGROUND: The aim of this study was to determine the sero-prevalence of Cag-A strains of Helicobacter pylori in both dyspeptic and non-dyspeptic individuals and also correlate the serological status of Gag-A strain of H. pylori with the various graded histological variables of chronic gastritis in the dyspeptic patients. METHODS: Using helicobacter p120 Cag-A enzyme linked immunosorbent assay, Cag-A serology test was carried out on 65 dyspeptic patients and 65 age and sex matched non-dyspeptic controls. The gastric biopsies of the patients were also histologically examined to ascertain the presence, nature and degree of the following histological variables of gastritis: colonisation by H. pylori; inflammation, intestinal metaplasia and mucosal atrophy. The CagA serological status was then correlated with the graded variables. RESULTS: A prevalence of 46.2% and 58.8% seropositivity for Cag-A strain of H. pylori was found among dyspeptic patients and control individuals respectively. Cag-A seropositive patients accounted for nine(81.8%) of the 11 cases with moderate to severe activity and 75% of both cases with mucosal atrophy and cases with intestinal metaplasia. CONCLUSION: Infection with Cag-A positive Helicobacter pylori was equally prevalent among both dyspeptic patients and control subjects studied. CagA seropositivity, however, appeared to be associated with higher inflammatory activity in the mucosa of patients with chronic gastritis and may be associated with intestinal metaplasia and mucosal atrophy in H. pylori-induced chronic gastritis.

The most appropriate site for endoscopic biopsy for the detection of H. pylori among Nigerians in Ibadan.

BACKGROUND: Helicobacter pylori is a significant aetiological factor for acid peptic diseases and gastric cancer. Detection of the organism in gastric mucosal biopsies is important, hence the need to ascertain the optimal site for biopsy that will facilitate identification of the organism. STUDY DESIGN: The study was carried out by obtaining directed gastric and duodenal endoscopic biopsies from twenty-five adult Nigerian patients clinically diagnosed to have gastroduodenitis at the University College Hospital, Ibadan, Nigeria. Biopsies were obtained from the gastric body, pyloric antrum, first and second parts of the duodenum at endoscopy. The biopsy specimens were tested for H. pylori by Campylobacter-like organism (CLO) test and histology. RESULTS: Positive results for H. pylori by CLO test were detected in 67% each for the biopsies taken from the gastric antrum and incisura angularis; and 28% and 17% for those taken from first and second parts of the duodenum respectively. There was no benefit in taking additional biopsy from incisura angularis to that from the antrum. Helicobacter pylori was better detected in the mucosa of the antrum (72%) than that of the duodenum (28%), p < 0.05. The organism was detected in 28% by histological examination of the tissue specimen of the patients compared to 72% by CLO test, p < 0.05. CONCLUSION: The study shows that the detection of H. pylori by invasive technique is better obtained by taking biopsy at the gastric antrum in Nigerian patients with gastroduodenitis. Furthermore, the CLO test yields more positive results than histological evaluation in the detection of the infection.

Comparison of three PCR methods for detection of Helicobacter pylori DNA and detection of cagA gene in gastric biopsy specimens.

AIM: To comparatively evaluate PCR and other diagnostic methods (the rapid urease test and / or culture) in order to determine which of the three PCR methods (ureA, glmM and 26-kDa, SSA gene) was most appropriate in the diagnosis of Helicobacter pylori (H pylori ) infection and also to evaluate the detection of a putative virulence marker of H pylori, the cagA gene, by PCR in biopsy specimens. METHODS: One hundred and eighty-nine biopsy specimens were collected from 63 patients (three biopsies each) undergoing upper gastroduodenal endoscopy for various dyspeptic symptoms. The PCR methods used to detect H pylori DNA directly from biopsies were the glmM, 26-kDa, ureA and then cagA was used to compare the culture technique and CLO for urease with the culture technique being used as the gold standard. RESULTS: Thirty-five percent of the biopsies were positive for H pylori DNA using the 3 PCR methods, while 68% of these were positive for the cagA gene. Twenty-four percent of the biopsies were negative for H pylori DNA in all PCR methods screened. The remaining 41% were either positive for ureA gene only, glmM only, 26-kDa only, or ureA + glmM, ureA + 26-kDa, glmM + 26-kDa. Out of the 35% positive biopsies, 41% and 82% were positive by culture and CLO respectively, while all negative biopsies were also negative by culture and cagA. Cag A+ infection was also predominantly found in H pylori DNA of the biopsies irrespective of the clinical diagnosis. CONCLUSION: This method is useful for correctly identifying infections caused by H pylori and can be easily applied in our laboratory for diagnostic purposes.

Helicobacter pylori infection in South Nigerians: a serological study of dyspeptic patients and healthy individuals.

Helicobacter pylori has now been well recognised to play a significant role in the pathogenesis of gastroduodenal disease. So far serology has been the most useful technique for rapid access to accurate information about H. pylori status of dyspeptic patients. This study reports on the seroprevalence of Hpylori infection in both dyspeptic and healthy adult Nigerian subjects in a community located in the South Western part of Nigeria. Two groups of subjects were studied, consisting of 25 adult Nigerian patients with dyspepsia who presented at the Gastroenterology Clinic, and 25 healthy adult Nigerian volunteers. Serum samples were prepared from five milliliters of blood collected from each of the subjects. The quantity of IgG antibodies to Hpylori was determined in each of these 50 samples, using the immunocomb II. Helicobacter pylori IgG kit, with each test result being validated by an internal controL Twenty-two (88%) of the 25 dyspeptic patients and 20 (80%) of the normal individuals were seropositive for IgG antibody to H. pylori. The difference in infection rate between both sexes was not statistically significant These results indicate a high rate of Hpylori infection in this locality as reported in previous serological studies in this country and some other developing countries. The similarly high seroprevalence of H. pylori infection in both our healthy individuals and dyspeptic patients also supports the assertion, earlier made in the literature, that H. pylori exerts its influence in concert with other environmental factors as well as social and genetic factors.

Relief to the scourge of primary hepatocellular carcinoma.

Primary hepatocellular carcinoma, a major global cause of morbidity and mortality presents a gloomy picture as many patients report late in hospital when routine modalities of therapy are no more applicable. Early diagnosis of the disease is facilitated by half-yearly liver ultrasonography and serological assay of alphafoetoprotein and ferritin in high risk groups. A relief to the scourge of the disease is the new modality radio frequency ablative therapy for both early and advanced diseases as well as recurrences. Prevention of primary hepatocellular carcinoma is by food hygiene, and alleviation of poverty along with governmental disposition to incorporating vaccination against Hepatitis B virus, the commonest aetiological factor, into the National Programme of immunization.

Interferon alfa-2a (Roferon-A) in the management of chronic hepatitis B infection: results of an open prospective study in Nigerian patients.

The efficacy and safety of recombinant interferon alfa-2a (rIFN) was evaluated in 26 adult Nigerian patients with chronic hepatitis B infection. Male and female patients with serological evidence of HBV infection (HBsAg and/or HBeAg positive patients) and abnormal liver histology were monitored for six months to confirm chronicity. At the end of the six months screening period eligible patient were enrolled into the study and treated with rIFN 4.5 MIU given three times a week for 6 months. Efficacy was assessed primarily by loss of HBV-DNA and/or HBeAg from serum and secondarily by loss of HBsAg and normalization of the liver histology. Safety was assessed by monitoring the leukocyte and platelet count over the treatment period whilst tolerability was assessed by recording the occurrence of adverse events (adverse drug reaction and intercurrent illness). At the end of therapy the response rate with respect to loss of HBV-DNA was 67% and 100% for HBeAg (i.e. for the six patients who were HBeAg positive at baseline). There was loss of HBsAg in 22.2% of the patients. A significant reduction in inflammation and necrosis scores was found among the 10 patients who had both baseline and term biopsies. The frequency of occurrence of adverse events was 53.8% and the laboratory safety parameters were not significantly affected by therapy (p > 0.05). 19.2% of the enrolled patients were withdrawn from the study prematurely. These results demonstrate that rIFN is effective in the management of CHB infection even in Nigerians. The high success rate associated with HBcAg clearance is particularly noteworthy.

Hepatitis B and C in doctors and dentists in Nigeria.

We surveyed a random sample (n = 75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAG), antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV), by enzyme immunoassay. The results suggest a high prevalence of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentists use universal precaution for protection against viral hepatitis on < 50% of the occasions when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeons, dentists) and lack of HBV vaccination (p < 0.05). After logistic regression, these factors were independently associated with HBV infection (p < 0.05). Sixty (80%) had not received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, < 37 years of age, and have fewer years of professional activity (p < 0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p < 0.05). To reduce the occupational exposure of HBV, universal precautions must be rigorously adhered to when the doctors and dentists carry out procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available.

Hepatitis B and C virus and hepatocellular carcinoma.

Antibody to hepatitis C virus (anti-HCV) was detected in 18.7% of patients with hepatocellular carcinoma (HCC) and in 10.9% of controls (P < 0.001). The corresponding prevalences of hepatitis B surface antigen (HBsAg) were 59.3% and 50.0% (P < 0.001). Using patients with non-hepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio 6.88%; 95% confidence interval [CI] 1.63-9.77) and HBsAg (odds ratio 6.46; 95% CI 1.68-18.13) were independent risk factors for HCC. Calculation of the incremental odds ratio indicated no interaction between hepatitis B virus (HBV) and HCV. Blood transfusion was a significant risk factor for acquiring HCV infection with odds ratios of 5.48 (95% CI 1.07-29.0) and 2.86 (95% CI 1.31-22.72) for HCC cases and controls, respectively. The mean age of HCC cases with HBsAg and anti-HCV was lower than that of HCC patients with anti-HCV alone (P < 0.01). It is concluded that there is a high rate of HBV infection, and a low rate of HCV infection, among Nigerian patients with HCC. However, HBV and HCV are independent risk factors for the development of HCC, with HBV having an effect more rapidly. Screening of blood products for transfusion might minimize the risk of HCV transmission.

The diagnostic utility of serum ferritin estimation in Nigerian patients with primary hepatocellular carcinoma.

Serum hepatitis B surface antigen (HBsAg) status and ferritin levels were measured in three groups of Nigerian subjects: Group A (n = 14) with non-neoplastic disease (CNLD); Group B (n = 14) with primary hepatocellular carcinoma (PHC); and Group C (n = 14) of healthy matched controls. Serum ferritin values were lowest in Group C, intermediate in Group A, and highest in the Group B patients (all p < 0.05). About 79% of the patients with PHC, 43% of those with CNLD, and none (0%) of the healthy controls had hyperferritinemia (serum ferritin > 400 ng/ml). Hyperferritinemia and HBsAg positivity coexisted in 15% and 73% of the patients with CNLD and PHC, respectively. Hyperferritinemia and HBsAg were significantly positively related in the patients with PHC (chi 2 5.09, p < 0.05). The predictive indices of hyperferritinemia in chronic liver disease appeared superior for PHC than for CNLD, and became somewhat enhanced with coexisting HBsAg positivity. These results suggest that serum ferritin could be useful as a tumor marker for PHC in Nigerian patients with established chronic liver disease.

The diagnostic utility of serum ferritin. Estimation in patients with primary hepatocellular carcinoma.

Serum hepatitis B surface antigen (HBsAg) status and ferritin levels were measured in 3 groups of subjects: Group A (n = 14) with chronic non-neoplastic liver disease (CNLD), Group B (n = 14) with primary hepatocellular carcinoma (PHC) and Group C (n = 14) comprising healthy matched controls without liver disease. Serum ferritin values were lowest in Group C, intermediate in Group A and highest in the Group B patients (all p < 0.05). About 79% of the patients with PHC, 43% of those with CNLD and none (0%) of the healthy controls, had hyperferritinaemia (serum ferritin > 400 ng/ml). Hyperferritinaemia and HBsAg positivity coexisted in 15% and 73% of the patients with CNLD and PHC, respectively. Hyperferritinaemia and HBsAg were significantly positively related in the patients with PHC (chi 2 5.09, p < 0.05). The predictive indices of hyperferritinaemia in chronic liver disease appeared superior for PHC than for CNLD, and became somewhat enhanced with coexisting HBsAg positivity. These results suggest that serum ferritin could be useful as a tumour marker for PHC in patients with established chronic liver disease.

Serum alphafoetoprotein, hepatitis B virus infection and primary hepatocellular carcinoma in Nigerians.

Serum alphafoetoprotein and hepatitis B antigen were estimated by radioimmuno-assay and haemagglutination methods respectively in 42 Nigerian adults comprising 14 subjects in each of three groups, viz, controls, liver cirrhosis and primary hepatocellular carcinoma. At an abnormal concentration of serum alphafoetoprotein greater than 200 micrograms/L, a correct diagnosis of primary liver cancer was made in 64.3% of the patients at a specificity of 100%. However, no correlation was found between serum concentrations of alphafoeto-protein and status of hepatitis B surface antigen in the patients with primary liver cancer. It may be concluded that serum alphafoeto-protein is useful in the diagnosis of primary hepatocellular carcinoma in Nigerians and secretion of the onco-foetal protein by neoplastic hepatocytes is unlikely to be influenced by hepatitis B virus infection.