Hepatitis B, C and D virus infections and risk of hepatocellular carcinoma in Africa: A meta-analysis including sensitivity analyses for studies comparable for confounders

Abstract

Introduction Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa. Methods Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses. Results A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7–105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2–15.6]) and DNA (OR = 8.9; 95% CI = [5.9–13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3–14.0]) and RNA (OR = 16.5; 95% CI = [7.8–34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9–112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3–387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0–13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6–10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4–13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results. Conclusions In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed.

Hepatocellular carcinoma in Hepatitis B and Human Immunodeficiency Virus coinfection in Africa: a focus on surveillance

“…In South Africa, many HBV infections aren’t discovered in PLWH until these individuals are diagnosed with HCC. As a result, many individuals appear with several lesions or large liver lesions on radiological examination, thus limiting the treatment options to palliative strategies [ 8 ] . Similarly, according to one study carried out in Egypt there is no efficient screening strategy for HCC in cirrhotic individuals with HIV, with only ~10% of new HCC detected during planned screening, while 38% of these patients had multiple liver tumors, and 72% had tumors greater than 5 cm in diameter [ 74 ] .…”

“…Africa and East Asia are estimated to account for more than 75% of global HCC patients [ 6 ] . Indeed, unique risk factors, such as a high prevalence of HIV in the context of HBV or hepatitis C (HCV) coinfection, as well as exposure to aflatoxins and underreported consumption of alcohol help explain the high incidence of HCC in these regions [ 6 – 8 ] . Moreover, the dynamics related to poor outcomes in HCC are increased in resource-limited settings including many parts of Africa, where most of HIV infections occur [ 9 , 10 ] .…”

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

“…Although the prevalence of NAFLD is increasing globally and emerging as a major cause of advanced liver diseases, effective and evidence-based pharmacotherapy is still lacking [ 4 ]. In viral hepatitis, potent antiviral therapy using nucleot(s)ide analogues and direct-acting antivirals (DAAs) is the mainstay treatment; however, only selected patients are candidates for antiviral therapy, and the supply of antiviral drugs is often limited in under-developed countries [ 5 , 6 ]. In addition, research has shown the combined fatty load in patients with viral hepatitis to have an unfavorable influence on long-term outcomes [ 7 ].…”

“…4 In viral hepatitis, potent antiviral therapy using nucleot(s)ide analogues and direct-acting antivirals (DAAs) is the mainstay treatment; however, only selected patients are candidates for antiviral therapy, and the supply of antiviral drugs is often limited in under-developed countries. 5,6 In addition, research has shown the combined fatty load in patients with viral hepatitis to have an unfavorable influence on long-term outcomes. 7 Therefore, varying drugs, including antidiabetics, antioxidants, lipid-lowering drugs, probiotics, and anti-platelets, which might have potential beneficial effects, have been continuously investigated in patients with CLD.…”

Clinical profiles and risk factors of hepatocellular carcinoma with viral hepatitis at a tertiary hospital in Mogadishu

“…In Africa, HBV and HCV are the primary HCC aetiologic agents (2,9,10), with over half of HCC cases caused by HBV, while approximately 25% are caused by HCV (10); however, in some African countries, Egypt in particular, HCV is the leading cause of HCC (11). Unfortunately, in Sub-Saharan Africa, most HCC diagnosis is made late in the disease cycle when surgery cannot be done.…”