Scielo RSS <![CDATA[SAMJ: South African Medical Journal]]> http://www.scielo.org.za/rss.php?pid=0256-957420180009&lang=en vol. 108 num. 8 lang. en <![CDATA[SciELO Logo]]> http://www.scielo.org.za/img/en/fbpelogp.gif http://www.scielo.org.za <![CDATA[<b>Mike Kew: A physician-scientist, teacher and role model extraordinaire with an enduring influence on excellence and mentorship in medicine</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900001&lng=en&nrm=iso&tlng=en <![CDATA[<b>Introduction</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900002&lng=en&nrm=iso&tlng=en <![CDATA[<b>Michael Charles Kew: A chronicle of his career</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900003&lng=en&nrm=iso&tlng=en <![CDATA[<b>Professor Mike Kew and the Royal Free Hospital</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900004&lng=en&nrm=iso&tlng=en <![CDATA[<b>Tributes from senior academics from the University of the Witwatersrand</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900005&lng=en&nrm=iso&tlng=en <![CDATA[<b>Tributes from the Gastroenterology Foundation of South Africa</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900006&lng=en&nrm=iso&tlng=en <![CDATA[<b>Towards the elimination of hepatitis B and hepatocellular carcinoma</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900007&lng=en&nrm=iso&tlng=en Hepatitis B (HBV) remains a global health problem despite the availability of effective vaccines since 1982 and effective antiviral therapy. The global burden of disease is substantial, with HBV resulting in 887 220 deaths in 2015: acute hepatitis (87 076), cirrhosis (462 690) and hepatocellular carcinoma (337 454). The World Health Organization has a vision to eliminate viral hepatitis as a public health threat by 2030. Although HBV and its associated complications of cirrhosis, liver failure and hepatocellular carcinoma are entirely vaccine preventable, there is no cure for chronic hepatitis B as yet. HBV elimination strategies will need to focus on effective and implementable preventive and therapeutic strategies such as upscaling HBV birth-dose vaccination, full HBV vaccine coverage, vaccination of high-risk groups, prevention of mother-to-child transmission, and identification of HBV-infected individuals and linkage to care with sustainable access to antiviral therapy. <![CDATA[<b>Molecular characteristics and clinical relevance of African genotypes and subgenotypes of hepatitis B virus</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900008&lng=en&nrm=iso&tlng=en Hepatitis B virus (HBV), a DNA virus, replicates via an RNA intermediate, through reverse transcription catalysed by the viral polymerase that lacks proof reading ability. Thus sequence heterogeneity is a feature of HBV being classified into at least 9 genotypes and over 35 subgenotypes. Africa has a high diversity of genotypes/subgenotypes, with distinct geographical distributions. Genotype A is found mainly in south-eastern Africa, E in western and central Africa and D prevailing in northern Africa. Outside Africa, subgenotype A2 prevails and A1 in Africa, which was the most probable source of its dispersal to Asia and Latin America, as a result of slave and trade routes. Genotype E is also an African strain with low genetic diversity, intimating a recent emergence of 200 years or less, with its dispersal outside Africa occurring as a result of modern human migrations. Carriers of subgenotype A1 and genotype E display unique clinical features. A1-infected individuals have low viral loads, low frequency of HBeAg-positivity, horizontal transmission of HBV, higher levels of liver damage and a higher risk of developing hepatocellular carcinoma. In contrast, individuals infected with genotype E have high viral loads, high frequency of HBeAg-positivity and transmit HBV perinatally. Although 15% of HBV infections in HIV-infected Africans are HBsAg-negative, the true occult phenotype of low viral loads is found in only 7% and 65% of individuals infected with subgenotype A1 and genotypes E (or D), respectively. Molecular and functional characteristics of these African HBV strains can account for their different clinical manifestations. <![CDATA[<b>Current and future directions for the management of hepatitis B</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900009&lng=en&nrm=iso&tlng=en Hepatitis B virus vaccination, while effective in reducing incident chronic hepatitis B in endemic regions, will not have the desired impact on the rates of end-stage liver disease in chronically infected persons. A large reservoir of chronic infection remains and needs to be managed effectively. Over three decades, interferon alpha (IFNcx), and nucleoside analogue therapies have reduced the morbidity and mortality associated with chronic hepatitis B by suppressing viral replication and retarding the progression to cirrhosis and the development of hepatocellular carcinoma (HCC). The preferential preservation of covalently closed circular (cccDNA) and capsid reverse transcriptase-cccDNA interactions during nucleoside analogue therapy currently prevent cure; the majority of patients require continuous maintenance suppressive therapy. In selected patients nucleoside analogues may be stopped. New targets for drug therapy need to be directed at inhibiting intracellular HBV replication, transcription and translation pathways to enhance the likelihood of a cure in the host. Such cures for chronic hepatitis B infection will require several synergistic therapies to achieve either complete eradication of replicative intermediates from the host (cure), or more probably, a functional cure defined as loss of hepatitis B surface antigen. Hampering such development is the lack of a proven serological surrogate for cccDNA to evaluate treatment efficacy. This review outlines the pathophysiology of the virus, the host immunological responses and current therapies. Understanding the interactions between HBV and the host remains fundamental to guide correct sequencing and combinations of treatment with either host or viral-targeting agents to achieve higher rates of cure. <![CDATA[<b>The global elimination of hepatitis C?</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900010&lng=en&nrm=iso&tlng=en Globally, 71 million people are thought to be viraemic for hepatitis C. The advent of short course all oral direct acting antiviral curative therapy for the virus has put the ideal of the global elimination of this virus within reach. Multiple efforts will be required to achieve this through identifying patients currently infected and preventing further transmission through rapid linkage to treatment while a vaccine remains tenaciously elusive. <![CDATA[<b>Hepatocellular carcinoma: Epidemiology, pathogenesis and surveillance - implications for sub-Saharan Africa</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900011&lng=en&nrm=iso&tlng=en Hepatocellular carcinoma (HCC) originates from hepatocytes usually secondary to chronic inflammation and cirrhosis. It is an important disease of global significance with a high incidence and mortality. It is the fifth and eighth most common cancer in males and females, respectively. HCC is also extremely lethal; in 2015 it was the second and sixth most common cause of death from cancer in males and females, respectively. Chronic viral hepatitis B and C are the most frequent risk factors for the development of HCC, and the global distribution of HCC largely mirrors that of chronic viral hepatitis. More recently, there has been a notable increase in the incidence of HCC as a result of obesity-related fatty liver disease. Here, we review the epidemiology of HCC, examine recent advances in our understanding of the pathogenesis of HCC, discuss the implications for identification of potential therapeutic targets, and provide the most updated recommendations on surveillance for HCC, with particular attention to the unique challenges and potential opportunities to reduce the burden of illness and death from HCC in sub-Saharan Africa. <![CDATA[<b>Molecular and cellular oncogenic mechanisms in hepatocellular carcinoma</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900012&lng=en&nrm=iso&tlng=en Hepatocellular carcinoma (HCC), as the fifth most diagnosed cancer in the world and the third leading cause of death, is a global health concern. Research stimulated by the dismal prognosis of HCC has led to significant advances in the understanding of its aetio-pathogenesis. Dysregulation of genetic, epigenetic and signalling pathways as well as tumour immunological escape mechanisms are implicated in the development of HCC. This review summarises the current knowledge of these mechanisms and argues that it is only through further understanding of their role in hepatocarcinogenesis, that new effective therapies can be developed. <![CDATA[<b>Prevention of hepatocellular carcinoma with antiviral therapy</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900013&lng=en&nrm=iso&tlng=en Chronic viral hepatitis types B and C may eventually lead to the development of hepatocellular carcinoma. Although hepatitis B is readily preventable by vaccination, there is growing evidence that antiviral therapy directed against hepatitis B may reduce the risk of liver cancer among those already infected. There is no vaccine against hepatitis C, but the evidence is now strong that antiviral therapy with sustained virological response (viral cure) reduces, but does not eliminate, the risk of hepatocellular carcinoma. <![CDATA[<b>Hepatocellular carcinoma in sub-Saharan Africa — the way forward</b>]]> http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900014&lng=en&nrm=iso&tlng=en Michael Kew's academic career spans five decades, representing the most proliferative and pioneering years of the expanded knowledge on all aspects of hepatocellular cancer (HCC). The preceding articles in this Festschrift bear testimony to his legacy, engagement, enthusiasm, dedication and ability to inspire others. His enormous contribution, mostly originating from research in sub-Saharan Africa (SSA), contributed immensely to the knowledge and evidence on which current understanding of the disease is based.