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 ( 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. (HEPATOLOGY 2014;60:1291-1301
Hepatocellular carcinoma (HCC) is a disease of global public health significance with mortality on the rise, despite the preventable nature of its risk factors especially in Africa. It is now the sixth most common cancer worldwide, fifth in males, and ninth in females. HCC incidence and mortality are predicted to increase in African countries constrained by limited resources to combat endemic levels of viral infection and synergistic environmental risk factors. The changing nature of HCC etiology is particularly illustrated here with the traditional risk factors like viral hepatitis coexisting alongside high human immunodeficiency virus (HIV) prevalence and rapidly increasing urbanization that have promoted a sharp increase in additional risk factors like coinfection, type 2 diabetes mellitus, and obesity. Although there are some differences in etiology between North Africa and sub-Saharan Africa, risk factors like chronic viral hepatitis B and C, aflatoxin exposure, and iron overload predominate. Aggressive hepatitis B genotypes, combined with hepatitis B virus/hepatitis C virus/HIV coinfections and aflatoxin exposure, promote a more aggressive molecular phenotype. In parallel to a better understanding of the molecular etiology of HCC, policy and planning initiatives to address the burden of HCC must be anchored within the reality of the limited resources available. Establishment and coordination of cancer registries across Africa is needed to improve the quality of data necessary to galvanize action. Preventive measures including hepatitis B vaccination programs, measures to prevent maternal-to-child and child-to-child transmission, delivery of universally accessible antiretroviral and antiviral treatments, and reduction of dietary aflatoxin exposure can contribute markedly to reduce HCC incidence. Finally, the development of biomarkers and new therapeutic interventions will need a better understanding of the unique genetic and epigenetic characteristics of HCC on the continent. We present a narrative review of HCC in Africa, discussing present and future trends.
In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5–20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5–62.2) and 90.0% (89.0–91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1–85.1) and 64.3% (62.8–65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.
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.
Background Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV‐infected individuals. We compared host and tumour characteristics between HIV‐infected and HIV‐uninfected Nigerians with HCC and examined the impact of HIV on survival. Methods This prospective observational study was conducted at Jos University Teaching Hospital in Jos, Nigeria, among adults (>18 years) with HCC enrolled between September 2015 and September 2017 and followed until April 2019. Demographics, tumour characteristics and survival were compared between HCC subjects with and without HIV. Results 101 (10 HIV‐infected and 91 HIV‐uninfected) subjects were enrolled [male 72%; median age 48 (IQR 35–60)]. 60% HIV‐infected subjects were receiving ART; 90% had CD4 counts ≥ 200/mm3 at HCC diagnosis, and 20% had HIV RNA levels < 20 copies/mL. 57.4% were infected with chronic HBV (HBsAg+). The duration of symptoms was shorter in HIV‐infected vs. HIV‐uninfected subjects [93 (IQR 54–132) vs. 155 (93–248] days; p = 0.02]. At the end of follow‐up, 99 of 101 (98.0%) subjects were confirmed to have died: 9 of 10 (90.0%) HIV‐infected and 90 of 91 (98.9%) HIV‐uninfected. The probability of survival at three months was 22% and 47% in HIV‐infected and HIV‐uninfected subjects, respectively (P = 0.02). Median time to death was significantly shorter in HIV‐infected vs. HIV‐uninfected subjects [24 days (IQR 16–88) vs. 85 days (IQR 34–178), respectively (P = 0.03)]. Conclusions High early mortality was observed in this cohort of Nigerian adults with HCC. HIV infection was associated with a faster clinical presentation and shorter survival. More aggressive HCC surveillance may be warranted in HIV‐infected subjects, particularly if they are co‐infected with chronic HBV.
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