The book comprehensively covers all aspects of hepatocellular carcinoma (cancer) as it occurs in sub-Saharan black Africans and how the cancer differs from that in other parts of the world, in most of which it occurs infrequently. The first chapter is introduced with a discussion of the difficulty in recording all cases of this cancer in sub Saharan Africa and then covers its epidemiology, emphasising the very high incidence of liver cancer in sub Saharan black Africans. The relatively young age at which the tumor occurs in comparison with the older age of the patients in resource-rich regions is stressed. The sex distribution of the cancer is also discussed. The second chapter describes the ways in which hepatocellular cancer presents in black Africans, its symptoms and signs, and how its presentation differs from that in other parts of the world. The third chapter summarises the grave outlook for patients with the tumor, the very short survival times of the patients, and the reasons for their deaths. The fourth chapter discusses the diagnosis of the cancer and why this is far more difficult than it is in resource-rich countries. The fifth chapter deals with the pathology of the tumor-its similarities and differences from that in other parts of the world. The sixth chapter is the longest in the book, and it deals comprehensively with the causes of liver cancer in sub-Saharan Africa. The major cause is chronic infection with the hepatitis B virus, an infection acquired in early childhood, and the possible mechanisms by which this may cause the cancer. Other less common but still important causes in the subcontinent-such as exposure to the fungal carcinogen, aflatoxin, chronic hepatitis C virus infection, dietary iron overload among Africans, and membranous obstruction of the inferior vena cava-are also discussed. The seventh chapter discusses the difficulty in treating hepatocellular cancer and the poor results

HEPATOCELLULAR CARCINOMA IN SUB-SAHARAN AFRICA

By Michael Charles Kew

Trafford Publishing

Copyright © 2012 Michael Charles Kew
All right reserved.
ISBN: 978-1-4669-1890-0

Contents

Dedication...........................................................................viiAcknowledgements.....................................................................ixForeword.............................................................................xiChapter 1 Epidemiology...............................................................1Chapter 2 Clinical Presentation......................................................24Chapter 3 Natural History, Prognosis, and Causes of Death............................69Chapter 4 Diagnosis..................................................................73Chapter 5 Pathology..................................................................98Chapter 6 Aetiology and Pathogenesis.................................................109Chapter 7 Treatment..................................................................205Chapter 8 Prevention, Screening and Surveillance.....................................218Chapter 9 Wither Hepatocellular Carcinoma In Sub-Saharan Africa?.....................251References...........................................................................255About The Author.....................................................................335

Chapter One

EPIDEMIOLOGY

INTRODUCTION

Africa is the second largest of the world's continents. It covers 30,300,000 square kilometers, approximately one-fifth of the global land area. The continent is sparsely inhabited, with a population of some 800 million people accounting for only 12% of the global population. Most of Africa's population lives to the south of the Sahara desert, where the vast majority of the inhabitants are Blacks. North Africa, in climate, customs, and cultural background, is Mediterranean rather than African, and almost every distinctive feature of cancer in Africa belongs to sub-Saharan Africa [Parkin et al, 2003]. None more so than hepatocellular carcinoma.

The global cancer burden has been, and will continue to be, increasingly influenced by the growth and aging of the world's population. In the year 2000, 10.1 million new cases of cancer were recorded worldwide, and this figure is expected to increase to 15 million by the year 2020 [Stewart and Kleihues, 2003]. Furthermore, by the year 2030 an annual total of 27 million new cases of cancer, 17 million deaths attributed to cancer, and 75 million people living with cancer could be expected [Boyle, 2006]. The impact of this increase will be felt in all geographical regions, but especially in the economically-constrained (low income; developing) regions, including sub-Saharan Africa.

To date, information on the occurrence of hepatocellular carcinoma in sub-Saharan Africa, in common with that on all cancers in the sub-continent, has been neither complete nor always accurate, as anyone who has ever tried to obtain accurate estimates of cancer incidences in the sub-continent will attest [Berman, 1951; Oettlé, 1964; Cook and Burkitt, 1971; Parkin et al, 2003]. As a result, the true incidence of hepatocellular carcinoma in sub-Saharan Africa has been significantly understated. Knowledge of cancer incidence and patterns in the African sub-continent has, until quite recently, been based largely on the work of a few pioneering clinicians and pathologists, who described series of cancer patients seen in their practices in terms of age, sex, cancer site, and histology [Berman, 1951; Oettlé, 1964; Cook and Burkitt, 1971]. Comparisons based on relative frequencies of different cancers in such case series may be misleading [Parkin et al, 2003]. Because biopsies and necropsies were, and to a lesser extent still are, seldom performed in Black African patients thought to be suffering from hepatocellular carcinoma, estimates of the occurrence of the tumor in the sub-continent, but particularly in rural areas where 80% of the Black population lives, under-estimate the true incidence of the tumor. Medical facilities in these rural areas are few and far between, and it has long been known that attendance at the local hospital decreases with its distance from the patient's home [Davies et al, 1965]. Furthermore, in the past, hepatocellular carcinoma has been, and even now is, often diagnosed solely on the basis of compatible clinical features, supported in some patients by either a raised serum -fetoprotein concentration or the finding of a mass-lesion in the liver on first-line ultrasonographic imaging of the liver [Kew, 2007]. The more sophisticated and expensive dynamic hepatic imaging techniques that today enable a firm diagnosis of hepatocellular carcinoma to be made on the basis of the early hypervascularity of the tumor followed by rapid wash-out of the indicator from the tumor are available in a few medical centers only in the large cities in sub-Saharan Africa, and certainly not in the rural areas.

Reports on hospital-based series of patients with hepatocellular carcinoma in the African sub-continent have been, and remain, biased by the interests and competence of the local clinicians, the diagnostic facilities and therapeutic options available, and the accuracy and completeness of record keeping [Oettlé, 1964; Parkin et al, 2003]. These short-comings are compounded by the nihilistic attitude of many doctors in sub-Saharan Africa to making a definitive diagnosis of hepatocellular carcinoma, which is engendered by the extremely poor results of treatment of this tumor and the dismal prognosis of the patients [Kew, 2007].

The appropriate statistic for comparing cancer risks between populations is the incidence rate [Parkin et al, 2003]. Incidence rates should be derived from population-based cancer registries, which aim to record information on all new cases of cancer that occur in a defined population [Parkin et al, 2003]. Accurate registration depends upon identifying every case of the cancer, which can only be achieved if patients have ready access to appropriate health services. When the necessary resources are inadequate, the number of patients with access to these services is limited and meaningful cancer registration is unlikely to be achieved [Oettlé, 1964; Parkin et al, 2003].

Another difficulty is to correctly identify the place of residence of cancer patients, so that when incidence rates are calculated, only those cases belonging to the population at risk are included [Flegg Mitchell, 1966; Parkin et al, 2003]. Unfortunately, place of residence is not an obvious concept in some sub-Saharan African regions. This is especially true in eastern and southern Africa, where Blacks living and working in urban areas often retain a foothold in their home village, to which they return intermittently on vacation. They may also return home to seek medical advice or care from the local traditional healers (witch-doctors; `nyangas'), or, when seriously ill or very old, to die [Flegg Mitchell, 1966]. Consequently, they may not be included in either an urban-based or a rural-based cancer registry. Moreover, many Black Africans living permanently in rural areas rely on the diagnostic and treatment services of traditional healers rather than conventional doctors [Flegg Mitchell, 1966] and they too would not be included in rural-based cancer registries. On the other hand, some Black men and women living in rural areas travel to towns or cities to stay with a relative when they are ill and need to visit a hospital. The address given to the hospital will be that of the urban...