ABSTRACT
UNLABELLED: There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program. Urinary proton nuclear magnetic resonance ((1) H-NMR) spectroscopy was used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC) healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC, 56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the initial cohort. The urinary metabotype of patients with HCC was distinct from those with Cir, DC, and NC with areas under the receiver operating characteristic (AUROC) curves of 0.86 (0.78-0.94), 0.93 (0.89-0.97), and 0.89 (0.80-0.98) in the training set and 0.81 (0.73-0.89), 0.96 (0.94-0.99), and 0.90 (0.85-0.96), respectively, in the validation cohort. A urinary metabolite panel, comprising inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA), showed a high sensitivity (86.9% [75.8-94.2]) and specificity (90.3% [74.2-98.0]) in the discrimination of HCC from cirrhosis, a finding that was corroborated in a validation cohort (AUROC: urinary panel = 0.72; AFP = 0.58). Metabolites that were significantly increased in urine of HCC patients, and which correlated with clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide, methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. CONCLUSION: The urinary metabotyping of this West African cohort identified and validated a metabolite panel that diagnostically outperforms serum AFP.
Subject(s)
Biomarkers, Tumor/urine , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Methionine/urine , Niacinamide/analogs & derivatives , Sarcosine/analogs & derivatives , alpha-Fetoproteins/urine , Acetylcarnitine/urine , Adolescent , Adult , Africa, Western/epidemiology , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/urine , Case-Control Studies , Choline/urine , Creatine/urine , Female , Humans , Ketoglutaric Acids/urine , Liver Neoplasms/epidemiology , Liver Neoplasms/urine , Male , Middle Aged , Niacinamide/urine , Phenotype , Reproducibility of Results , Sarcosine/urine , Sensitivity and Specificity , Young AdultABSTRACT
BACKGROUND: International partnerships in research are receiving ever greater attention, given that technology has diminished the restriction of geographical barriers with the effects of globalisation becoming more evident, and populations increasingly more mobile. DISCUSSION: In this article, we examine the merits and risks of such collaboration even when strict universal ethical guidelines are maintained. There has been widespread examples of outcomes beneficial and detrimental for both high and low -income countries which are often initially unintended. SUMMARY: The authors feel that extreme care and forethought should be exercised by all involved parties, despite the fact that many implications from such international work can be extremely hard to predict. However ultimately the benefits gained by enhancing medical research and philanthropy are too extensive to be ignored.
Subject(s)
Biomedical Research , Cooperative Behavior , Developed Countries , Developing Countries , Global Health , International Cooperation , Poverty , Biomedical Research/ethics , Humans , IncomeABSTRACT
BACKGROUND & AIMS: Cholangiocarcinomas (CC) can be sub-divided into intrahepatic (IHCC) or extrahepatic (EHCC). Hilar or 'Klatskin' tumours are anatomically extrahepatic. Most international studies, also from the UK, report increasing IHCC and decreasing EHCC incidence. The second edition of the International Classification of Diseases for Oncology (ICD-O-2) assigned 'Klatskin' tumours a unique histology code (8162/3), but this was cross-referenced to the topography code for intrahepatic (IHBD) rather than extrahepatic bile duct tumours (EHBD). Under the third ICD-O edition, 'Klatskin' tumours are cross-referenced to either IHBD or EHBD. New editions of the ICD-O classification are adopted at different time points by different countries. We investigated the impact of changing ICD-O classifications and the potential misclassification of hilar/'Klatskin' tumours on bile duct tumour and CC incidence rates in England and Wales and the US. We also examined whether coding practices by cancer registries in England and Wales could be influencing these rates. METHODS: We analysed age-standardised incidence rates (ASIR) in England and Wales for IHBD and EHBD tumours between 1990 and 2008, then transferred all 'Klatskin' tumours from IHBD to EHBD and reanalysed rates from 1995, when ICD-O-2 was introduced in the UK. We also compared trends in IHBD, EHBD, and 'Klatskin' tumours in England and Wales with those in the USSEER (Surveillance, Epidemiology and End Results) database. Coding practice at Cancer registry level in England and Wales was investigated via a questionnaire completed by all national cancer registries. RESULTS: In England and Wales, 1990-2008, ASIR of IHBD cancers rose (0.43-1.84/100,000 population in males; 0.27-1.51 in females) but fell for EHBD (0.78-0.51/100,000 population in males; 0.62-0.39 in females). After transferring all 'Klatskin' tumours from IHBD to EHBD, there remained a marked increase in ASIR of IHBD cancers and a decrease in ASIR for EHBD, as only 1% of CC were reportedly 'Klatskin'. The US SEER data showed that ASIR for IHBD gradually rose from 0.59/100,000 population in 1990 to 0.91 in 2001, then sharply fell before plateauing at 0.60 by 2007. ASIR for EHBD remained relatively stable at around 0.80/100,000 population until 2001, then began increasing, to 0.97 by 2007. Annually, between 1995 and 2008, the vast majority of 'Klatskin' tumours in England and Wales were coded as IHBD. This was also the case in the SEER data until 2001, when the situation was reversed and subsequently most 'Klatskin' tumours were coded as EHBD. US trends coincide with a switch from ICD-O2 to ICD-O-3 in 2001. In the UK, the switch to ICD-O-3 only occurred in 2008. On questioning, cancer registries in England and Wales stated they would not code a CC described as 'hilar' with the designated 'Klatskin' histology code. If the tumour site is unspecified, most registries classify CC as intrahepatic. CONCLUSIONS: Changes in ICD-classification may be influencing observed changes in IHBD and EHBD incidence rates. Coding misclassification is likely to have been skewing CC registration to an intrahepatic site, thereby contributing to the previously reported rise in intrahepatic tumours.
Subject(s)
Bile Duct Neoplasms/classification , Bile Duct Neoplasms/epidemiology , Bile Ducts, Intrahepatic , Cholangiocarcinoma/classification , Cholangiocarcinoma/epidemiology , Adult , Aged , Aged, 80 and over , England/epidemiology , Female , Humans , Incidence , Klatskin Tumor/classification , Klatskin Tumor/epidemiology , Male , Middle Aged , Registries , Retrospective Studies , SEER Program/statistics & numerical data , Surveys and Questionnaires , United States/epidemiology , Wales/epidemiologyABSTRACT
Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy worldwide. Current serum diagnostic biomarkers, such as alpha-fetoprotein, are expensive and insensitive in early tumor diagnosis. Urinary biomarkers differentiating HCC from chronic liver disease would be practical and widely applicable. Using an 11.7T nuclear magnetic resonance system, urine was analyzed from three well-matched subject groups, collected at Jos University Teaching Hospital (JUTH), Nigeria. Multivariate factor analyses were performed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). All patients were of Nigerian descent: 18 hepatitis B surface antigen (HBsAg)-positive patients with HCC, 10 HBsAg positive patients with cirrhosis, and 15 HBsAg negative healthy Nigerian controls. HCC patients were distinguished from healthy controls, and from the cirrhosis cohort, with sensitivity/specificity of 100%/93% and 89.5%/88.9%, respectively. Metabolites that most strongly contributed to the multivariate models were creatinine, carnitine, creatine and acetone. Urinary (1)H MRS with multivariate statistical analysis was able to differentiate patients with HCC from normal subjects and patients with cirrhosis. Creatinine, carnitine, creatine and acetone were identified as the most influential metabolites. These findings have identified candidate urinary HCC biomarkers which have potential to be developed as simple urinary screening tests for the clinic.
Subject(s)
Biomarkers/urine , Carcinoma, Hepatocellular/urine , Liver Neoplasms/urine , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Female , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Multivariate Analysis , NigeriaABSTRACT
Irritable bowel syndrome (IBS) is a common disorder in the Western world. Its prevalence is yet to be fully determined in the African setting. This was a cross-sectional study of patients attending three General Outpatient clinics in Jos, Nigeria. Four hundred and eighteen randomly selected patients were interviewed using a structured questionnaire based on the Rome II diagnostic criteria for IBS. Excluded from the study were patients with established organic disease, memory problems, and pregnant women. Eighteen patients were excluded based on these criteria and 400 were analysed using Epi Info 2000 (Atlanta, Georgia, USA) statistical computer software. One hundred and thirty-two (33%) out of the 400 patients fulfilled the criteria for the diagnosis of IBS, the female to male ratio being 1.13 : 1. IBS was significantly associated with increasing age (P=0.03) and depression (P<0.001). The prevalence of IBS is high among patients attending primary care in the African setting with depression being the likely reason for seeking care.
Subject(s)
Irritable Bowel Syndrome/epidemiology , Adolescent , Adult , Cross-Sectional Studies , Depression/epidemiology , Depression/etiology , Female , Humans , Irritable Bowel Syndrome/psychology , Male , Middle Aged , Nigeria/epidemiology , Outpatient Clinics, Hospital , PrevalenceABSTRACT
Nigeria is the most populous country in Africa but, despite extensive oil deposits, little of the country's recently found wealth has filtered through into the healthcare sector. Nigerian hospitals are poorly equipped and infrastructure for interventional procedures is mostly lacking. Liver disease is common, owing to the high prevalence of hepatitis B and hepatitis C, which often coexist with HIV infection. Antiviral treatments are expensive and drugs are commonly unavailable, even if they can be afforded. Therapy for end-stage liver disease is difficult, since endoscopic services are not widespread. A new training programme for oesophageal variceal band ligation at Jos University Teaching Hospital, Central Nigeria, aided by educational bursaries from the Royal College of Physicians, however, provides some promise in improving healthcare standards. The work of agencies, such as the Tropical Health and Educational Trust has fostered direct one-to-one links between UK hospitals and healthcare workers in a variety of African countries and offers a model for future development, albeit on a local, rather than a national or international, basis.
Subject(s)
Liver Diseases/epidemiology , Carcinoma, Hepatocellular , Endoscopy, Gastrointestinal , Esophageal and Gastric Varices , Hepatitis, Viral, Human , Humans , Liver Diseases/drug therapy , Liver Diseases/surgery , Nigeria/epidemiologyABSTRACT
BACKGROUND/AIMS: Previous studies have observed disturbances in the 1H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment. METHODS: Patients with HCC (53) and cirrhosis (26) and healthy volunteers (19) were recruited from Nigeria and Egypt. Participants provided serum or plasma samples, which were analysed using 600 MHz 1H NMR spectroscopy with nuclear Overhauser enhancement spectroscopy pulse sequences. Median group spectra comparison and multivariate analysis were performed to identify regions of difference. RESULTS: Significant differences between HCC patients and healthy volunteers were detected in levels of low density lipoprotein (P = 0.002), very low density lipoprotein (P < 0.001) and lactate (P = 0.03). N-acetylglycoproteins levels in HCC patients were significantly different from both healthy controls and cirrhosis patients (P < 0.001 and 0.001). CONCLUSION: Metabotype differences were present, pointing to disturbed lipid metabolism and a switch from glycolysis to alternative energy metabolites with malignancy, which supports the Warburg hypothesis of tumour metabolism.
ABSTRACT
AIM: To study the brain-gut interaction and the effect of behavioral or psychiatric conditions on irritable bowel syndrome (IBS) in an African population. METHODS: IBS was diagnosed using the Rome II diagnostic criteria. The entry of each patient was confirmed following detailed explanations of the questions. Four hundred and eighteen patients were studied. Subjects satisfying the Rome II criteria for IBS were physically examined and stool microscopy was done to identify the presence of "alarm factors". Depression was diagnosed using the symptom-check list adapted from the Research Diagnostic Criteria (DSM-IV) of the American Psychiatric Association. RESULTS: Seventy-five (56.8%) of the 132 IBS patients were depressed whereas only 54 (20.1%) of the 268 non-IBS patients were depressed. There was a significant relationship between IBS and depression (chi2 = 54.29, Odds ratio = 5.21, 56.8 +/- 8.4 vs 20.1 +/- 5.2, P = 0.001). Even though constipation predominant IBS patients were more likely to be depressed, no significant relationship was found between the subtype of IBS and depression (chi2 = 0.02, OR = 0.95, P = 0.68). CONCLUSION: IBS is significantly associated with major depression but not gender and bowel subtypes of the patients. Patients with IBS need to be evaluated for depression due to the highly significant relationship between the two conditions.
Subject(s)
Depression/epidemiology , Depression/psychology , Irritable Bowel Syndrome/psychology , Adolescent , Adult , Age Distribution , Cross-Sectional Studies , Depression/etiology , Female , Humans , Irritable Bowel Syndrome/complications , Male , Middle Aged , Nigeria/epidemiology , Odds Ratio , Prevalence , Sex DistributionABSTRACT
BACKGROUND: Discriminatory metabolic profiles have been described in urinary 1H nuclear magnetic resonance (NMR) spectroscopy studies of African patients with hepatocellular carcinoma (HCC). This study aimed to assess similarities in a UK cohort, where there is a greater etiological diversity. METHODS: Urine from cirrhosis and HCC patients was analyzed using a 600 MHz 1H NMR system. Multivariate analysis and median group MR spectra comparison identified metabolite alterations between groups. Metabolite identification was achieved through literature reference and statistical total correlation spectroscopy. Diagnostic accuracy was compared to serum alpha-fetoprotein (AFP). RESULTS: Of the 52 patients recruited, 13 samples from HCC and 25 from cirrhosis patients were selected. At 200 IU mL-1, diagnostic sensitivity of AFP was 27%. Multivariate analysis of urinary spectra generated diagnostic models with a sensitivity/specificity of 53.6%/96%. p-Cresol sulfate (P = 0.04), creatinine (P = 0.03), citrate (P = 0.21) and hippurate (P = 0.52) were reduced in the HCC patients. Carnitine (P = 0.31) and formate (P = 0.44) were elevated. CONCLUSION: Diagnostic sensitivity was lower than previous African studies, but still outperformed serum AFP. Reduced creatinine, citrate and hippurate and elevated carnitine are comparable with the African studies. p-Cresol sulfate alteration is a novel finding and may indicate an altered sulfonation capacity of the liver in patients with HCC.
ABSTRACT
Hepatocellular carcinoma (HCC) exhibits a huge disease burden on West Africa, with a large proportion of all HCC cases worldwide occurring in the sub-region. The high HCC prevalence is due to the endemicity of a number of risk factors, most notably hepatitis B, C and HIV. West African HCC also displays a poor prognosis. Generally speaking, this is owing to more aggressive tumours, late patient presentation and inadequate management. Exposure to chronic viral hepatitis, more carcinogenic West African strains of hepatitis B virus and carcinogens such as aflatoxin B1 all encourage tumour growth. Lack of patient confidence in the healthcare system contributes to poor health-seeking behaviors and management of the disease can be lacking, due in part to poor health infrastructure, resources available and lack of access to expensive treatment. There is also much we do not know about West African HCC, especially the effect rising obesity and alcohol use may have on this disease in the future. Suggestions for improvement are discussed, including surveillance of high-risk groups. Although there is much to be done before West African HCC is thought to be a curable disease, many steps have been taken to move in the right direction.
ABSTRACT
PURPOSE: The estimation of the degree of liver fibrosis is important for prognosis, surveillance, and treatment of chronic liver disease. Although liver biopsy is the gold standard for diagnosis, it is subject to sampling error, while ultrasound-based techniques, such as Acoustic Radiation Force Impulse (ARFI) and transient elastography, have gained popularity. However, no previous comparative study has performed these ultrasound techniques at the time of biopsy. The aim of this study was to compare the reliability of these techniques to define the severity of liver fibrosis in viral hepatitis patients. PATIENTS AND METHODS: We compared liver transient elastography and Acoustic Radiation Force Impulse measurements, performed along the intended biopsy track, with liver biopsy results in 46 viral hepatitis patients, all measured on the same morning. Fibrosis was measured by histology using the Ishak fibrosis staging. RESULTS: The relative sensitivity and specificity of different incremental cut-off values for both techniques, and the predictive ability of pairwise comparison of the 3 tests (including APRI) and of their combined use with more severe grades of histology-measured liver fibrosis, show that the single variable with greatest sensitivity and specificity is TE with a cut-off of >10.0. CONCLUSION: Transient elastography has a better performance than ARFI, which has a lower sensitivity, in the diagnosis of severe stages of fibrosis. Also ARFI of the spleen is correlated with Ishak fibrosis staging, and could be a possible additional tool for the diagnosis of liver fibrosis.
Subject(s)
Biopsy/methods , Liver Cirrhosis/pathology , Liver/pathology , Spleen/pathology , Adult , Elasticity Imaging Techniques , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND/AIMS: The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development. METHODS: HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice. Five of these rats were concomitantly administered oral norfloxacin. Six Fischer non-treated rats acted as healthy controls. Proton nuclear magnetic resonance (NMR) spectra were acquired using a 600 MHz NMR system. RESULTS: Control animals were 120 g heavier than diseased counterparts. Proton NMR spectra from diseased rats displayed significant decreases in lipoproteins, unsaturated fatty acids, acetyl-glycoprotein, acetoacetate, and glucose (P ≤ 0.001). Plasma citrate and formate levels were increased (P = 0.02). Norfloxacin appeared to abrogate this effect slightly. CONCLUSION: The spectral profiles of plasma in rats with HCC display marked changes with relation to lipid metabolism and cellular turnover. Norfloxacin appears to moderate these metabolic alterations to a small degree.
ABSTRACT
The incidence of hepatocellular carcinoma (HCC) is known to be high in West Africa with an approximate yearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B (HBV), environmental food contaminants (aflatoxins), poor management of predisposing risk factors and poorly-managed strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include: (1) high rate of risk factors; (2) failure to identify at risk populations; (3) lack of effective treatment; and (4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.
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AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD. CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.
Subject(s)
Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/epidemiology , Liver Neoplasms/mortality , Age Distribution , Black People , Carcinoma, Hepatocellular/ethnology , Caribbean Region , Databases, Factual , England/epidemiology , Ethnicity , Female , Humans , Incidence , Least-Squares Analysis , Liver Neoplasms/ethnology , Male , Registries , Sex Distribution , Wales/epidemiology , White PeopleABSTRACT
BACKGROUND: Hepatitis B has been reported to be high in HIV-infected African populations. However, the impact of this co-infection on the survival of HIV-infected Africans on long-term highly active antiretroviral therapy (HAART) remains poorly characterised. We investigated the impact of HBV/HIV co-infection on survival of HIV infected patients undergoing antiretroviral therapy in a West African population. METHODS: This was a clinic-based cohort study of HIV-infected adults enrolled in Nigeria, West Africa. Study subjects (9,758) were screened for hepatitis B and hepatitis C at HAART initiation. Kaplan-Meier survival and Cox proportional hazards models were used to estimate probability of survival and to identify predictors of mortality respectively, based on hepatitis B surface antigen status. All patients had signed an informed written consent before enrolment into the study; and we additionally obtained permission for secondary use of data from the Harvard institutional review board. RESULTS: Patients were followed up for a median of 41 months (interquartile range: 30-62 months) during which, 181 (1.9%) patients died. Most of the deaths; 143 (79.0%) occurred prior to availability of Tenofovir. Among those that were on antiretroviral therapy, hepatitis B co-infected patients experienced a significantly lower survival than HIV mono-infected patients at 74 months of follow up (94% vs. 97%; p=0.0097). Generally, hepatitis B co-infection: HBsAg-positive/HIV-positive (Hazards Rate [HR]; 1.5: 95% CI 1.09-2.11), co-morbid tuberculosis (HR; 2.2: 95% CI 1.57-2.96) and male gender (HR; 1.5: 95% CI 1.08-2.00) were significantly predictive of mortality. Categorising the patients based on use of Tenofovir, HBV infection failed to become a predictor of mortality among those on Tenofovir-containing HAART. CONCLUSIONS: HBsAg-positive status was associated with reduced survival and was an independent predictor of mortality in this African HIV cohort on HAART. However, Tenofovir annulled the impact of HBV on mortality of HIV patients in the present study cohort.
ABSTRACT
BACKGROUND: Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. METHODS: Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. RESULTS: Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. CONCLUSIONS: The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Proteome , Proteomics , Adult , Africa, Western , Apolipoprotein A-I/blood , Apolipoprotein A-I/metabolism , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnosis , Case-Control Studies , Complement C3/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Hemopexin/metabolism , Hepatitis B, Chronic/complications , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Liver Neoplasms/blood , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Male , Mass Spectrometry , Middle Aged , Proteomics/methods , ROC Curve , Reproducibility of Results , Young Adult , alpha 1-Antitrypsin/blood , alpha 1-Antitrypsin/metabolismABSTRACT
Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. The majority of HCC occurs on a background of cirrhosis, principally caused by two major risk factors, chronic hepatitis B and hepatitis C infection. Current diagnostic modalities, of ultrasound and α-fetoprotein, are expensive and lack sensitivity in tumour detection. Early diagnosis is integral to improved survival rates and there have been recent advances in technology that have enabled early identification of the process of hepatocarcinogenesis. This review outlines the epidemiological trends and risk factors for HCC; diagnostic techniques and current guidelines for screening and surveillance; and newer methods of screening.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Mass Screening/methods , Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/epidemiology , Diagnostic Imaging , Genomics , Humans , Incidence , Liver Neoplasms/epidemiology , Metabolomics , Population Surveillance , Practice Guidelines as Topic , Prevalence , Prognosis , Risk FactorsABSTRACT
INTRODUCTION: Previous sentinel surveys of HIV in Nigeria studied pregnant women attending antenatal care, thereby omitting other important high-risk groups. We therefore investigated the prevalence of HIV/AIDS in low- and high-risk populations in the state of Plateau, Nigeria. METHODOLOGY: Blood samples were collected by venepuncture from 5,021 adults aged ≥ 15 years between August and October 2008. At least one major town and one rural community were selected in each Local Government Area (LGA). Samples were initially screened with a rapid HIV testing kit; reactive samples were further tested using Stat Pak. Discordant samples were confirmed using Genie-II. RESULTS: Of 5,021 subjects screened, 245 (4.88%) were seropositive. Local Government prevalence ranged from 0.68% in Bassa to 16.07% in Jos North. On average, LGAs in the Southern Senatorial Zone had higher rates. Most (over 80%) positive cases were younger than 40 years. Females had a significantly higher (6.85%) prevalence than males (2.72%). Age-specific prevalence was higher among females aged 25 to 29 years (2.09%). Risk factors identified for acquisition of HIV infection were previous history of STDs (6, 16.28%); men having sex with men (2, 11.76%); having multiple sexual partners (97; 10.49%); intravenous drug use (10, 7.58%); sharing of sharp objects (20, 4.82%); and history of blood transfusion (21, 3.65%). CONCLUSION: The seemingly higher prevalence recorded in this survey could be attributed to the inclusion of high- and low-risk groups in the general population, unlike previous reports which studied only antenatal care attendees. This survey provides useful baseline information for further studies.
Subject(s)
HIV Infections/epidemiology , Adolescent , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Nigeria/epidemiology , Pregnancy , Seroepidemiologic Studies , Sex Factors , Young AdultSubject(s)
Carcinoma, Hepatocellular/prevention & control , Hepatitis B/complications , Liver Cirrhosis/prevention & control , Liver Neoplasms/prevention & control , Africa, Western/epidemiology , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Cooperative Behavior , Hepatitis B/epidemiology , Humans , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Liver Neoplasms/epidemiology , Liver Neoplasms/virologyABSTRACT
BACKGROUND: Irritable bowel syndrome (IBS) has been reported to be common in the West. Community surveys are lacking in the African setting. We determined the prevalence of IBS in a rural community setting in Nigeria. METHOD: Questionnaires were administered to consenting individuals. Subjects satisfying the Rome II criteria for IBS were invited for physical examination at a health center to identify the presence of "alarm factors." RESULTS: One hundred forty (31.6%) of the 443 evaluated individuals fulfilled the Rome II criteria for IBS, with a male-to-female ratio of 1.37:1 (P= .11). The prevalence of IBS was highest (39.3%) in the third decade, followed by 25% in the fourth decade (P= .009). Ninety-six (67%) IBS individuals had the alternating pattern of diarrhea and constipation, whereas 28 (20%) and 19 (13%) had constipation and diarrhea subtypes, respectively. CONCLUSION: IBS as diagnosed by the Rome II criteria has a high prevalence in the African rural population, as obtained elsewhere.