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Journal of Digestive Diseases 2015; 16; 152–158
doi: 10.1111/1751-2980.12223
Original article
Liver cancer in Malaysia: Epidemiology and clinical presentation in a multiracial Asian population Khean-Lee GOH, Hamizah RAZLAN, Juanda Leo HARTONO, Choon-Seng QUA, Boon-Koon YOONG, Peng-Soon KOH & Basri Johan Jeet ABDULLAH Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
OBJECTIVE: Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians. METHODS: Consecutive patients with HCC were prospectively studied from 2006 to 2009. HCC was diagnosed principally on multiphasic computed tomography and magnetic resonance imaging scans of the liver. The tumor was staged according to the Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Altogether, 348 patients were diagnosed with HCC. There were 239 (68.7%) Chinese patients, 71 (20.4%) Malays and 38 (10.9%) Indians, with the median age of 62.5 years and the male to female ratio of 3.4:1. The predominant etiology in Malay and KEY WORDS:
CONCLUSIONS: HCC is most common among Chinese, followed by Malays and Indians in Malaysia. The etiology of HCC shows a peculiar racial pattern.
BCLC staging, Chinese, hepatocelluar carcinoma, Indian, Malay, multiracial Asian population.
INTRODUCTION Hepatocellular cancer (HCC) is a major cancer in the world today. According to the World Health Organization Globocan 2012 statistics, HCC is the fifth most Correspondence to: Khean-Lee GOH, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Email: [email protected] Conflict of interest: None. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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Chinese patients was hepatitis B virus infection (>60%) and in Indian patients was alcohol intake (26.3%) and cryptogenic cause (29.0%). Hepatitis C was seen in 18.3% of Malays, but less than 10% in Chinese and Indians. BCLC staging was: Stage A, 120 (34.5%); Stage B, 75 (21.6%); Stage C, 84 (24.1%); and Stage D, 69 (19.8%). A larger proportion of Indian than Chinese and Malays patients (44.7%) presented with stage D disease. Portal vein invasion was noted in 124 patients (35.6%) and extrahepatic metastases in 68 (19.5%). Surgical resection and radiofrequency ablation with curative intent was carried out in >90% of stage A patients and transarterial chemoembolization in 49.3% and 21.4% of stages B and C patients, respectively.
common cancer in men, with 554 000 cases representing 7.5% of the total cancer burden and the ninth in women, with 228 000 cases constituting 3.4% of the global cancer burden.1 There is marked geographical variation in the epidemiology of this cancer. The regions of highest incidence are in the Asia–Pacific region: East Asia and Southeast Asia, as well as in Central and Western Africa, where about 85% of the cases occur. Agestandardized incidence rates (ASR) in excess of 40 per 100 000 per year have been reported in some
Journal of Digestive Diseases 2015; 16; 152–158 countries. Conversely, low rates are reported from the Western countries, with ASR of less than 10 per 100 000 per year.1 HCC is a common cancer among the ethnic Chinese in Malaysia. The ASR is particularly high in elder Chinese men aged >60 years where an ASR of 46.2 per 100 000 per year has been reported,2 in keeping with the figures of ethnic Chinese from the Mainland China, Taiwan, China and other high-incidence countries and regions in East Asia, such as Japan and Korea.1 Malaysia epitomizes a multiracial Asian population in Southeast Asia and consists of three major Asian races: Malay, Chinese and Indian, who live together in the same country. Differences exist in the epidemiology of various gastrointestinal diseases including gastric and colorectal cancers and Helicobacter pylori infection.3–5 Small-scale epidemiological surveys on chronic viral hepatitis B have shown that there is a higher prevalence of these diseases among the Chinese than the Malays and Indians.6,7 A recent publication by our group has further discussed the peculiar epidemiology of liver cirrhosis with distinct differences in etiological factors between races in our multiracial population.8 With these differences in mind, we carried out a survey on HCC with regards to the demographic characteristics of the patients and the etiology, clinical presentations and staging of the disease in a local Malaysian population seeking medical care in our hospital. PATIENTS AND METHODS Consecutive patients presenting with HCC at the University of Malaya Medical Centre (Kuala Lumpur, Malaysia) from 2006 to 2009 were prospectively recruited for this study. Liver cancer was diagnosed using the American Association for the Study of Liver Diseases (AASLD) guidelines9 on a multiphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) when lesions were seen larger than 2 cm in diameter and showing characteristic arterial hypervascularity and washout during the venous phase with an α-fetoprotein (AFP) level > 200 ng/mL. Lesions of less than 2 cm in diameter or did not display the characteristic pattern described above were subjected to liver biopsy for confirmation. Patients’ demographic details, medical history, AFP levels and viral serology were noted. The presence of cirrhosis and the Child–Pugh Classification of the patients was recorded. A careful review of CT or MRI
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was also carried out by a dedicated liver radiologist and the size, location, number of tumor lesions and portal vein invasion were noted. The staging of the tumor was carried out according to the Barcelona Clinic Liver Cancer (BCLC) classification.10 The study was approved by the Ethics Committee of the University of Malaya Medical Centre and the study was performed according to the International Conference on Harmonization Good Clinical Practice guidelines. Statistical analysis Statistical analyses were performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). Continuous parameters were expressed as mean ± standard deviation, and categorical variables were expressed as numbers and percentages or frequencies. Comparison between the two groups was carried out using the χ2 test or Fisher’s exact test, where appropriate. P < 0.05 was considered statistically significant. RESULTS Over the period of the study 348 patients were diagnosed with HCC. The baseline demographic data of the patients are shown in Table 1. Most of the patients were at the elder age, with a median age of 62.5 years (25–75% quartiles 54–69 years). Men outnumbered women in a ratio of 3.4:1. Chinese (n = 239, 68.7%) constituted the overwhelming majority of our patients, followed by Malays (n = 71, 20.4%) and Indians (n = 38, 10.9%). The prevalences of HCC according to racial group for the same period of time per 10 000 hospital admissions were: Malays 14.5 (71/48 849), Chinese 65.2 (239/36 682) and Indians 11.5 (38/33 076). The differences in prevalence rates between Chinese and the other two races were highly significant (both P < 0.001); however, there was no significant difference between Malays and Indians (P = 0.241). Table 1. Basic demographic characteristics of patients (N = 348) Characteristics Age, years (median [25–75% quartiles]) Male : female Ethnicity, n (%) Malays Chinese Indians
N = 348 62.5 (54–69) 269:79 71 (20.4) 239 (68.7) 38 (10.9)
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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Etiological factors
Presentations of HCC
Overall, the most common etiology for HCC in our patients was hepatitis B virus (HBV) infection, which accounted for 59.2% of our patients (Table 2). Among the Chinese patients, hepatitis B accounted for 157 (65.7%) of HCC patients; in 7 (2.9%) chronic hepatitis B was concomitant with heavy alcohol intake and 6 (2.5%) were co-infected with hepatitis C virus (HCV). Cryptogenic origin, hepatitis C and heavy alcohol intake as the sole etiological factor were found in only 33 (13.8%), 22 (9.2%) and 10 (4.2%) of Chinese patients, respectively. While hepatitis B (n = 43, 60.6%) was also the major etiological agent in Malay patients; hepatitis C was the sole etiology in 13 (18.3%) and another 13 (18.3%) of the patients had a cryptogenic etiology. Among the Indians, on the other hand, 6 (15.8%) patients were infected with HBV alone, while 10 (26.3%) were due to heavy alcohol intake and 11 (29.0%) to a cryptogenic cause. Hepatitis C as the sole etiology accounted for only 2 (5.3%) of the Indians. A heavy alcohol intake together with hepatitis B and C were seen in 3 (7.9%) and 4 (10.5%) patients, respectively. Only one Indian and one Chinese patient had previously diagnosed autoimmune hepatitis and primary biliary cirrhosis, respectively.
The first clinical presentation of patients is shown in Table 3. Almost one-third of the patients (n = 109; 31.3%) were asymptomatic and their HCC was detected incidentally. Upper abdominal pain was reported in 86 (24.7%) patients. A further 59 (17.0%) complained of non-specific abdominal discomfort with wind and bloating that were consistent with dyspeptic symptoms. Altogether 29 (8.3%) patients presented with weight loss only, 19 (5.5%) presented with variceal bleeding, 16 (4.6%) with jaundice and 30 (8.6%) having pre-existing cirrhosis presented with deterioration of their liver function, including worsening of jaundice, abdominal distension/swelling. Therefore, 18.7% (65/348) of these patients presented with some complication or deterioration of liver disease.
Table 2.
Overall and race-based etiologies for hepatocellular carcinoma
Etiology, n (%) Hepatitis B Hepatitis C Cryptogenic Alcohol Hepatitis B + C Alcohol + hepatitis B Alcohol + hepatitis C Primary biliary cirrhosis Autoimmune hepatitis
Table 3.
There were no significant differences in the patients’ clinical presentations among the three races. The proportion of Indian HCC patients presenting with complicated liver disease (jaundice, encephalopathy, variceal bleeding and deterioration of known liver disease) was higher than that of Malays and Chinese (29.0% [11/38] vs 22.5% [16/71] and 15.9% [38/ 239], respectively). The difference between Indian and Chinese patients with respect to this issue was almost significant with a P value of 0.051. Most of the Indian
Overall (n = 348)
Malays (n = 71)
Chinese (n = 239)
Indians (n = 38)
206 (59.2) 37 (10.6) 57 (16.4) 21 (6.0) 7 (2.0) 11 (3.2) 7 (2.0) 1 (0.3) 1 (0.3)
43 (60.6) 13 (18.3) 13 (18.3) 1 (1.4) 0 (0) 1 (1.4) 0 (0) 0 (0) 0 (0)
157 (65.7) 22 (9.2) 33 (13.8) 10 (4.2) 6 (2.5) 7 (2.9) 3 (1.3) 1 (0.4) 0 (0)
6 (15.8) 2 (5.3) 11 (29.0) 10 (26.3) 1 (2.6) 3 (7.9) 4 (10.5) 0 (0) 1 (2.6)
First clinical presentation of patients
n (%) Asymptomatic Abdominal pain Abdominal discomfort and bloating Weight loss Liver failure/encephalopathy (deterioration of known liver cirrhosis) Jaundice Variceal bleeding
Overall (n = 348)
Malays (n = 71)
Chinese (n = 239)
Indians (n = 38)
109 (31.3) 86 (24.7) 59 (17.0) 29 (8.3) 30 (8.6)
13 (18.3) 22 (31.1) 15 (21.1) 5 (7.0) 11 (15.5)
90 (37.6) 58 (24.3) 32 (13.4) 21 (8.8) 12 (5.0)
6 (15.8) 6 (15.8) 12 (31.5) 3 (7.9) 7 (18.4)
16 (4.6) 19 (5.5)
3 (4.2) 2 (2.8)
11 (4.6) 15 (6.3)
2 (5.3) 2 (5.3)
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 152–158
Liver cancer in Malaysia
patients (54.5% [6/11]) in this category had heavy alcohol intake-related liver cirrhosis and had sought medical treatment late in their illness. Most asymptomatic patients (67/109) presented with incidental findings on ultrasonography of the liver with or without the elevation of AFP levels. Thirty-five (32.1%) patients presented with elevated AFP levels (>200 ng/mL). Surveillance Overall, only 74 of 348 (21.3%) patients were on any sort of surveillance program with doctors for liver disease. Among the Chinese patients, 58 (24.3%) were detected on surveillance, compared with Malay (n = 11, 15.5%) and Indians (n = 5, 13.2%). Surveillance for HCC was carried out predominantly among hepatitis B patients and mainly in Chinese patients. However, of the hepatitis B patients, only 57 of 206 (27.7%) patients were on regular follow up in a special hepatitis B surveillance clinic. Of the asymptomatic patients 55 (50.5%) were detected on surveillance but this constituted only 15.8% of the whole group of HCC patients. Presence and severity of cirrhosis Most of the patients (313/348) were cirrhotic at the diagnosis of HCC; among them, 138 (39.7%), 106 (30.5%) and 69 (19.8%) were classified as Child-Pugh Class A, B and C. Table 4.
Stage Stage Stage Stage
Extent and staging of tumor The extent of tumor was staged according to the BCLC classification (Table 4). Altogether, 120 (34.5%) of patients were classified as early HCC (stage A) and 75 (21.6%) and 84 (24.1%) were classified as stages B and C, respectively. A total of 19.8% of our patients presented with stage D disease. Portal vein invasion was noted in 124 (35.6%) patients. Racial differences in the staging of disease were seen. The proportion of Chinese (40.6% vs 7.9%, P < 0.001) and Malays (28.2% vs 7.9%, P = 0.014) patients with stage A disease was significantly higher than Indians. The difference between Chinese and Malay patients, however, did not reach statistical significance (P = 0.060). At the same time, the proportion of Indians with stage D disease was significantly higher than that of the Chinese (44.7% vs 13.8%, P < 0.001) and Malays (44.7% vs 13.8%, P < 0.001 and 44.7% vs 26.7%; P = 0.010). The difference between Indians and Malays, however, did not reach statistical significance (P = 0.058). BCLC staging and first treatment received (Table 5) As shown in Table 5, among the stage A patients, 41 (34.2%) underwent surgical resection, 72 (60.0%) underwent radiofrequency ablation (RFA) and the other 7 (5.8%) refused RFA therapy or surgery and underwent alternative treatment and chemotherapy or were lost to follow up. Of stage B patients, 37 (49.3%) underwent transarterial chemoembolization (TACE) and 14 (18.7%) received RFA treatment, while one
Barcelona Clinic Liver Cancer staging, n (%)
A B C D
Table 5.
155
Overall (n = 348)
Malay (n = 71)
Chinese (n = 239)
Indian (n = 38)
120 (34.5) 75 (21.6) 84 (24.1) 69 (19.8)
20 (28.2) 12 (16.9) 20 (28.2) 19 (26.7)
97 (40.6) 55 (23.0) 54 (22.6) 33 (13.8)
3 (7.9) 8 (21.1) 10 (26.3) 17 (44.7)
Barcelona Clinic Liver Cancer (BCLC) staging and treatment Treatments
BCLC staging A (N = 120) B (N = 120) C (N = 84) D (N = 69)
Surgery
TACE
RFA
Systemic chemotherapy
Other/ palliative
41 (34.2) 0 (0) 0 (0) 0 (0)
0 (0) 37 (49.3) 18 (21.4) 0 (0)
72 (60.0) 14 (18.7) 4 (4.8) 0 (0)
0 (0) 1 (1.3) 0 (0) 0 (0)
7 (5.8) 23 (30.7) 62 (73.8) 69 (100)
RFA, radiofrequency ablation; TACE, transarterial chemoembolization.
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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Journal of Digestive Diseases 2015; 16; 152–158
underwent systemic chemotherapy and 23 (30.7%) refused further treatment or underwent palliative or alternative therapy. Most patients with stage C disease (62/84, 73.8%) received only palliative or alternative medical treatment. However, 18 (21.4%) patients with stage C underwent TACE and the other 4 (4.8%) underwent RFA. Targeted chemotherapy with sorafenib was prescribed in only 5 (6.0%) patients with stage C HCC. All 69 patients in stage D received palliative and supportive therapy. AFP levels AFP levels varied widely from 0 to >2 ×106 ng/mL, with a median value of 200 ng/mL (25–75% quartiles 18–4000 ng/mL). Exactly half the patients exceeded the arbitrary cut-off level of >200 ng/mL. The range of AFP levels according the BCLC staging are shown in Table 6. The proportion of patients with elevated AFP levels ≥200 ng/mL was significantly higher in stage C and D than in stage A and B (P < 0.001). There were no significant differences in the AFP levels between stages A and B or C and D, respectively. Tumor metastasis Tumor metastasis was noted in 68 (19.5%) patients (Table 7). The lungs were the most common site of metastasis, with solitary or multiple nodules seen in 61 (17.5%) patients, followed by tumor metastasis to Table 6. The range of α-fetoprotein (AFP) levels according the BCLC staging AFP levels (ng/mL)
BCLC stage, n (%)
1000
A (N = 120) B (N = 75) C (N = 84) D (N = 69)
83 (69.2) 47 (62.7) 22 (26.2) 25 (36.2)
16 (13.3) 9 (12.0) 12 (14.3) 10 (14.5)
21 (17.5) 19 (25.3) 50 (59.5) 34 (49.3)
Table 7.
Tumor metastasis (N = 348) n (%)†
Lungs Bone Para vertebral mass Intra-abdominal lymph nodes Adrenal Mediastinal lymph nodes No documented metastasis
61 (17.5) 16 (4.6) 3 (0.9) 32 (9.2) 4 (1.1) 4 (1.1) 280 (80.5)
†Metastasis in more than one location in some patients.
intra-abdominal lymph nodes in 32 (9.2%) and to bone in 16 (4.6%), while metastases to the adrenals (1.1%), paravertebral area (0.9%) and mediastinal lymph nodes (1.1%) were also observed. DISCUSSION Liver cancer is an important cancer in Malaysia that places a huge burden on the country’s health resources. Although it ranks only as the sixth most frequent cancer, HCC is the second most common cancer in the digestive tract following colorectal cancer in Malaysian men.3 The frequency of cancer follows a racial pattern, with the Chinese being affected most, followed by the Malays and Indians, as is shown in our hospital admission prevalence statistics and is confirmed by the National Cancer Registry Database.2,3 We have previously reported and discussed quite extensively the epidemiology of liver cirrhosis in Malaysia.8 The etiological factors in the different racial groups showed an interesting and peculiar pattern, reflecting the different epidemiology of chronic viral hepatitis B and C, alcohol intake and diabetes mellitus among the different races in this country.8 In this study, we have again shown that, similar to liver cirrhosis, among Chinese and Malays HBV infection is the main etiological factor. In contrast, among Indians, alcohol intake and cryptogenic cause accounted for over 50% of the cases. We have discussed previously the peculiar epidemiology of heavy alcohol intake in the country, which appears to be confined to socioeconomically poor Indians presenting with liver cirrhosis.8 HBV infection continues to be the most important cause of chronic liver disease in Malaysia. Despite the introduction of mass vaccination of newborns in 1989 in the country, the reservoir of HBV infection in the middle and elder age adult population remains large and will presumably only start to decline in 2050. Although HCV infection was found in a significant proportion of Malay patients with HCC (18.3%), it is significantly lower in both Indian and Chinese patients. Overall, HCV infection was found in only 10.6% of our HCC cases and is not an important cause of chronic liver disease or HCC in Malaysia. This is in contrast to those reported in the Western countries and Japan, where hepatitis C is a major cause of chronic liver disease and the most frequent cause of HCC.11,12 On the other hand, 16.4% of all HCC patients was cryptogenic. We have shown that most patients in this
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 152–158 category had a history of long-standing diabetes mellitus and presumably had pre-existing non-alcoholic fatty liver disease. With the increasing incidence of diabetes mellitus13–15 and the high prevalence of fatty liver in our population, and especially among Malays and Indians, as shown in our recent publication,16 the proportion of HCC patients with associated nonalcoholic fatty liver disease and the overall number of HCC cases appear likely to increase dramatically. It is also important to note that Malays constitute up to 60% of our population, showing that the increase in absolute number of cases and the overall health burden in the country would be quite marked. Clinical presentations of our patients are protean. Nearly one-third of our patients were asymptomatic at presentation and were detected incidentally with an abdominal mass on clinical examination, a lesion at ultrasonography or on the detection of elevated AFP level. Only one-quarter of the patients presented with abdominal pain, while a significant proportion (17.0%) presented with abdominal discomfort and distension rather than actual pain. Interestingly, a small but significant proportion of patients (8.3%) presented with only weight loss. Only 18.7% of patients presented with some specific liver-related complaint and 8.6% were detected in patients with already established liver cirrhosis and failure. The early detection of HCC remains the key to a favorable treatment outcome of HCC. The hepatitis B surveillance clinic has been in existence in our hospital since 1984; the original aim being to review and follow up ‘blood bank-screened’ HBV-positive individuals. This clinic has now been expanded for the surveillance of all chronic viral hepatitis patients. AFP levels and ultrasonography of the liver are carried out in patients at regular intervals (usually at 6-monthly intervals). It is disappointing, however, to note that only a small proportion of patients (15.8%) were detected on a surveillance clinic follow up. The rate of HCC detection through surveillance is low among all three races, although it is higher in the Chinese, as the proportion of hepatitis B is higher in this racial group and proportionately more are therefore likely to attend the hepatitis B surveillance clinic follow up. One-third of our patients were staged with BCLC stage A, almost half with stages B and C, and 19.8% were classified as BCLC stage D. Of the three races, it is interesting to note that the proportion of Indian patients presenting with stage D disease was significantly higher than the Malays and Chinese. This can
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be explained by the fact that most Indian patients are poor and seek healthcare at a late stage of disease. It also reflects the predominant underlying etiology of HCC. Many Indian patients with HCC present with decompensated alcoholic cirrhosis and liver cancer is detected only at that point in time. The treatment of HCC reflects the availability of local expertise and resources. Overall, relatively few of our patients underwent curative resection. Of the BCLC stage A patients, only 34.2% of them underwent surgery whereas more than half underwent RFA. Liver transplantation is not established in Malaysia for the treatment of liver cancer and is not available in our medical center. Of the stage B and C patients, onethird underwent TACE, while many patients opted for alternative or mainly supportive therapy. In our local setting both RFA and TACE are frequently used with the availability of a dedicated interventional hepatobiliary radiology team. However, both procedures remain expensive. Since 2008 TACE has been carried out with drug-eluting beads and doxorubicin, which has added to the overall cost of the procedure. This has invariably influenced the choice of treatment of many of our patients, who have opted for various alternative traditional types of therapies which are less expensive. Targeted chemotherapy was only recently introduced in Malaysia in 2009 and, together with the high cost of therapy, has understandably been used in only a minority of patients. To our knowledge, this is a first report on HCC from Malaysia. Our study described the real-life clinical experience of a busy general hospital and although it is a single center study, we feel it reliably reflects the epidemiology, clinical features and treatment approaches to the disease in this country at the current time. Despite the increased awareness of hepatitis B and C among the public and the health profession, a significant proportion of patients present late with the advanced liver cancer. This has restricted their choice of treatment options. The proportion of hepatitis B-related HCC will invariably decline with the effect of mass vaccination on all newborns implemented in the country since 1989. However, at the same time, the increase in diabetes mellitus and the high prevalence of fatty liver disease, especially among the Indians and Malays, is greatly worrying16 and portends a marked increase in chronic liver disease cirrhosis and cancer in Malaysia. The increase in the prevalence of obesity and fatty liver is a global phenomenon. Obesity is already regarded
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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as occurring in epidemic proportions in the Asia– Pacific region17 and perhaps a harbinger of an epidemic of HCC in the future.18 REFERENCES 1 World Health Organization International Agency for Cancer Research. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Cited: 29 January 2015. Available from URL: http://globocan.iarc .fr/accessed 2 Lim GCC, Halimah Y, eds. Second Report of the National Cancer Registry. Cancer Incidence in Malaysia 2003. Kuala Lumpur: National Cancer Registry, 2004. 3 Ariffin Z, Nor Saleha IT. National Cancer Registry Report 2007. Ministry of Health, Malaysia, 2011. 4 Goh KL, Cheah PL, Md N, Quek KF, Paraskathi N. Ethnicity and H. pylori as risk factors for gastric cancer in Malaysia: A prospective case control study. Am J Gastroenterol 2007; 102: 40–5. 5 Goh KL, Parasakthi N. The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial South–East Asian country. Eur J Gastroenterol Hepatol 2001; 13: 177–83. 6 Tan TC, Vadivale M, Ong CN. Prevalence of hepatitis B surface antigen and antibody among health care employees in Negri Sembilan, Malaysia, 1989. Asia Pac J Public Health 1992–1993; 6: 134–9. 7 Yap SF. Chronic hepatitis B infection in Malaysians. Malays J Pathol 1994; 16: 3–6. 8 Qua CS, Goh KL. Liver cirrhosis in Malaysia: peculiar epidemiology in a multiracial Asian country. J Gastroenterol Hepatol 2011; 26: 1333–7. 9 Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases.
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Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208–36. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999; 19: 329–38. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med 2000; 160: 3227–30. Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology 2002; 62 (Suppl 1): 8–17. Khebir BV, Osman A, Khalid BA. Changing prevalence of diabetes mellitus amongst rural Malays in Kuala Selangor over a 10-year period. Med J Malaysia 1996; 51: 41–7. Chiam P, Abdullah F, Chow HK, Adeeb SM, Yousafzai MS. The ethnic characteristics and prevalence of diabetes mellitus, hypertension and hyperlipidaemia in patients who underwent coronary artery bypass grafting in Hospital Universiti Kebangsaan Malaysia. Med J Malaysia 2002; 57: 460–6. Rampal S, Rampal L, Rahmat R et al. Variation in the prevalence, awareness, and control of diabetes in a multiethnic population: a nationwide population study in Malaysia. Asia Pac J Public Health 2010; 22: 194–202. Goh SC, Ho ELM, Goh KL. Prevalence and risk factors of non-alcoholic fatty liver disease in a multiracial suburban Asian population in Malaysia. Hepatol Int 2013; 7: 548–54. Yoon KH, Lee JH, Kim JW et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006; 368: 1681–8. Goh LY, Goh KL. Obesity: an epidemiological perspective from Asia and its relationship to gastrointestinal and liver cancers. J Gastroenterol Hepatol 2013; 28 (Suppl 4): 54–8.
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 152–158
doi: 10.1111/1751-2980.12223
Original article
Liver cancer in Malaysia: Epidemiology and clinical presentation in a multiracial Asian population Khean-Lee GOH, Hamizah RAZLAN, Juanda Leo HARTONO, Choon-Seng QUA, Boon-Koon YOONG, Peng-Soon KOH & Basri Johan Jeet ABDULLAH Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
OBJECTIVE: Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians. METHODS: Consecutive patients with HCC were prospectively studied from 2006 to 2009. HCC was diagnosed principally on multiphasic computed tomography and magnetic resonance imaging scans of the liver. The tumor was staged according to the Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Altogether, 348 patients were diagnosed with HCC. There were 239 (68.7%) Chinese patients, 71 (20.4%) Malays and 38 (10.9%) Indians, with the median age of 62.5 years and the male to female ratio of 3.4:1. The predominant etiology in Malay and KEY WORDS:
CONCLUSIONS: HCC is most common among Chinese, followed by Malays and Indians in Malaysia. The etiology of HCC shows a peculiar racial pattern.
BCLC staging, Chinese, hepatocelluar carcinoma, Indian, Malay, multiracial Asian population.
INTRODUCTION Hepatocellular cancer (HCC) is a major cancer in the world today. According to the World Health Organization Globocan 2012 statistics, HCC is the fifth most Correspondence to: Khean-Lee GOH, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Email: [email protected] Conflict of interest: None. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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Chinese patients was hepatitis B virus infection (>60%) and in Indian patients was alcohol intake (26.3%) and cryptogenic cause (29.0%). Hepatitis C was seen in 18.3% of Malays, but less than 10% in Chinese and Indians. BCLC staging was: Stage A, 120 (34.5%); Stage B, 75 (21.6%); Stage C, 84 (24.1%); and Stage D, 69 (19.8%). A larger proportion of Indian than Chinese and Malays patients (44.7%) presented with stage D disease. Portal vein invasion was noted in 124 patients (35.6%) and extrahepatic metastases in 68 (19.5%). Surgical resection and radiofrequency ablation with curative intent was carried out in >90% of stage A patients and transarterial chemoembolization in 49.3% and 21.4% of stages B and C patients, respectively.
common cancer in men, with 554 000 cases representing 7.5% of the total cancer burden and the ninth in women, with 228 000 cases constituting 3.4% of the global cancer burden.1 There is marked geographical variation in the epidemiology of this cancer. The regions of highest incidence are in the Asia–Pacific region: East Asia and Southeast Asia, as well as in Central and Western Africa, where about 85% of the cases occur. Agestandardized incidence rates (ASR) in excess of 40 per 100 000 per year have been reported in some
Journal of Digestive Diseases 2015; 16; 152–158 countries. Conversely, low rates are reported from the Western countries, with ASR of less than 10 per 100 000 per year.1 HCC is a common cancer among the ethnic Chinese in Malaysia. The ASR is particularly high in elder Chinese men aged >60 years where an ASR of 46.2 per 100 000 per year has been reported,2 in keeping with the figures of ethnic Chinese from the Mainland China, Taiwan, China and other high-incidence countries and regions in East Asia, such as Japan and Korea.1 Malaysia epitomizes a multiracial Asian population in Southeast Asia and consists of three major Asian races: Malay, Chinese and Indian, who live together in the same country. Differences exist in the epidemiology of various gastrointestinal diseases including gastric and colorectal cancers and Helicobacter pylori infection.3–5 Small-scale epidemiological surveys on chronic viral hepatitis B have shown that there is a higher prevalence of these diseases among the Chinese than the Malays and Indians.6,7 A recent publication by our group has further discussed the peculiar epidemiology of liver cirrhosis with distinct differences in etiological factors between races in our multiracial population.8 With these differences in mind, we carried out a survey on HCC with regards to the demographic characteristics of the patients and the etiology, clinical presentations and staging of the disease in a local Malaysian population seeking medical care in our hospital. PATIENTS AND METHODS Consecutive patients presenting with HCC at the University of Malaya Medical Centre (Kuala Lumpur, Malaysia) from 2006 to 2009 were prospectively recruited for this study. Liver cancer was diagnosed using the American Association for the Study of Liver Diseases (AASLD) guidelines9 on a multiphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) when lesions were seen larger than 2 cm in diameter and showing characteristic arterial hypervascularity and washout during the venous phase with an α-fetoprotein (AFP) level > 200 ng/mL. Lesions of less than 2 cm in diameter or did not display the characteristic pattern described above were subjected to liver biopsy for confirmation. Patients’ demographic details, medical history, AFP levels and viral serology were noted. The presence of cirrhosis and the Child–Pugh Classification of the patients was recorded. A careful review of CT or MRI
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was also carried out by a dedicated liver radiologist and the size, location, number of tumor lesions and portal vein invasion were noted. The staging of the tumor was carried out according to the Barcelona Clinic Liver Cancer (BCLC) classification.10 The study was approved by the Ethics Committee of the University of Malaya Medical Centre and the study was performed according to the International Conference on Harmonization Good Clinical Practice guidelines. Statistical analysis Statistical analyses were performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA). Continuous parameters were expressed as mean ± standard deviation, and categorical variables were expressed as numbers and percentages or frequencies. Comparison between the two groups was carried out using the χ2 test or Fisher’s exact test, where appropriate. P < 0.05 was considered statistically significant. RESULTS Over the period of the study 348 patients were diagnosed with HCC. The baseline demographic data of the patients are shown in Table 1. Most of the patients were at the elder age, with a median age of 62.5 years (25–75% quartiles 54–69 years). Men outnumbered women in a ratio of 3.4:1. Chinese (n = 239, 68.7%) constituted the overwhelming majority of our patients, followed by Malays (n = 71, 20.4%) and Indians (n = 38, 10.9%). The prevalences of HCC according to racial group for the same period of time per 10 000 hospital admissions were: Malays 14.5 (71/48 849), Chinese 65.2 (239/36 682) and Indians 11.5 (38/33 076). The differences in prevalence rates between Chinese and the other two races were highly significant (both P < 0.001); however, there was no significant difference between Malays and Indians (P = 0.241). Table 1. Basic demographic characteristics of patients (N = 348) Characteristics Age, years (median [25–75% quartiles]) Male : female Ethnicity, n (%) Malays Chinese Indians
N = 348 62.5 (54–69) 269:79 71 (20.4) 239 (68.7) 38 (10.9)
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Etiological factors
Presentations of HCC
Overall, the most common etiology for HCC in our patients was hepatitis B virus (HBV) infection, which accounted for 59.2% of our patients (Table 2). Among the Chinese patients, hepatitis B accounted for 157 (65.7%) of HCC patients; in 7 (2.9%) chronic hepatitis B was concomitant with heavy alcohol intake and 6 (2.5%) were co-infected with hepatitis C virus (HCV). Cryptogenic origin, hepatitis C and heavy alcohol intake as the sole etiological factor were found in only 33 (13.8%), 22 (9.2%) and 10 (4.2%) of Chinese patients, respectively. While hepatitis B (n = 43, 60.6%) was also the major etiological agent in Malay patients; hepatitis C was the sole etiology in 13 (18.3%) and another 13 (18.3%) of the patients had a cryptogenic etiology. Among the Indians, on the other hand, 6 (15.8%) patients were infected with HBV alone, while 10 (26.3%) were due to heavy alcohol intake and 11 (29.0%) to a cryptogenic cause. Hepatitis C as the sole etiology accounted for only 2 (5.3%) of the Indians. A heavy alcohol intake together with hepatitis B and C were seen in 3 (7.9%) and 4 (10.5%) patients, respectively. Only one Indian and one Chinese patient had previously diagnosed autoimmune hepatitis and primary biliary cirrhosis, respectively.
The first clinical presentation of patients is shown in Table 3. Almost one-third of the patients (n = 109; 31.3%) were asymptomatic and their HCC was detected incidentally. Upper abdominal pain was reported in 86 (24.7%) patients. A further 59 (17.0%) complained of non-specific abdominal discomfort with wind and bloating that were consistent with dyspeptic symptoms. Altogether 29 (8.3%) patients presented with weight loss only, 19 (5.5%) presented with variceal bleeding, 16 (4.6%) with jaundice and 30 (8.6%) having pre-existing cirrhosis presented with deterioration of their liver function, including worsening of jaundice, abdominal distension/swelling. Therefore, 18.7% (65/348) of these patients presented with some complication or deterioration of liver disease.
Table 2.
Overall and race-based etiologies for hepatocellular carcinoma
Etiology, n (%) Hepatitis B Hepatitis C Cryptogenic Alcohol Hepatitis B + C Alcohol + hepatitis B Alcohol + hepatitis C Primary biliary cirrhosis Autoimmune hepatitis
Table 3.
There were no significant differences in the patients’ clinical presentations among the three races. The proportion of Indian HCC patients presenting with complicated liver disease (jaundice, encephalopathy, variceal bleeding and deterioration of known liver disease) was higher than that of Malays and Chinese (29.0% [11/38] vs 22.5% [16/71] and 15.9% [38/ 239], respectively). The difference between Indian and Chinese patients with respect to this issue was almost significant with a P value of 0.051. Most of the Indian
Overall (n = 348)
Malays (n = 71)
Chinese (n = 239)
Indians (n = 38)
206 (59.2) 37 (10.6) 57 (16.4) 21 (6.0) 7 (2.0) 11 (3.2) 7 (2.0) 1 (0.3) 1 (0.3)
43 (60.6) 13 (18.3) 13 (18.3) 1 (1.4) 0 (0) 1 (1.4) 0 (0) 0 (0) 0 (0)
157 (65.7) 22 (9.2) 33 (13.8) 10 (4.2) 6 (2.5) 7 (2.9) 3 (1.3) 1 (0.4) 0 (0)
6 (15.8) 2 (5.3) 11 (29.0) 10 (26.3) 1 (2.6) 3 (7.9) 4 (10.5) 0 (0) 1 (2.6)
First clinical presentation of patients
n (%) Asymptomatic Abdominal pain Abdominal discomfort and bloating Weight loss Liver failure/encephalopathy (deterioration of known liver cirrhosis) Jaundice Variceal bleeding
Overall (n = 348)
Malays (n = 71)
Chinese (n = 239)
Indians (n = 38)
109 (31.3) 86 (24.7) 59 (17.0) 29 (8.3) 30 (8.6)
13 (18.3) 22 (31.1) 15 (21.1) 5 (7.0) 11 (15.5)
90 (37.6) 58 (24.3) 32 (13.4) 21 (8.8) 12 (5.0)
6 (15.8) 6 (15.8) 12 (31.5) 3 (7.9) 7 (18.4)
16 (4.6) 19 (5.5)
3 (4.2) 2 (2.8)
11 (4.6) 15 (6.3)
2 (5.3) 2 (5.3)
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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patients (54.5% [6/11]) in this category had heavy alcohol intake-related liver cirrhosis and had sought medical treatment late in their illness. Most asymptomatic patients (67/109) presented with incidental findings on ultrasonography of the liver with or without the elevation of AFP levels. Thirty-five (32.1%) patients presented with elevated AFP levels (>200 ng/mL). Surveillance Overall, only 74 of 348 (21.3%) patients were on any sort of surveillance program with doctors for liver disease. Among the Chinese patients, 58 (24.3%) were detected on surveillance, compared with Malay (n = 11, 15.5%) and Indians (n = 5, 13.2%). Surveillance for HCC was carried out predominantly among hepatitis B patients and mainly in Chinese patients. However, of the hepatitis B patients, only 57 of 206 (27.7%) patients were on regular follow up in a special hepatitis B surveillance clinic. Of the asymptomatic patients 55 (50.5%) were detected on surveillance but this constituted only 15.8% of the whole group of HCC patients. Presence and severity of cirrhosis Most of the patients (313/348) were cirrhotic at the diagnosis of HCC; among them, 138 (39.7%), 106 (30.5%) and 69 (19.8%) were classified as Child-Pugh Class A, B and C. Table 4.
Stage Stage Stage Stage
Extent and staging of tumor The extent of tumor was staged according to the BCLC classification (Table 4). Altogether, 120 (34.5%) of patients were classified as early HCC (stage A) and 75 (21.6%) and 84 (24.1%) were classified as stages B and C, respectively. A total of 19.8% of our patients presented with stage D disease. Portal vein invasion was noted in 124 (35.6%) patients. Racial differences in the staging of disease were seen. The proportion of Chinese (40.6% vs 7.9%, P < 0.001) and Malays (28.2% vs 7.9%, P = 0.014) patients with stage A disease was significantly higher than Indians. The difference between Chinese and Malay patients, however, did not reach statistical significance (P = 0.060). At the same time, the proportion of Indians with stage D disease was significantly higher than that of the Chinese (44.7% vs 13.8%, P < 0.001) and Malays (44.7% vs 13.8%, P < 0.001 and 44.7% vs 26.7%; P = 0.010). The difference between Indians and Malays, however, did not reach statistical significance (P = 0.058). BCLC staging and first treatment received (Table 5) As shown in Table 5, among the stage A patients, 41 (34.2%) underwent surgical resection, 72 (60.0%) underwent radiofrequency ablation (RFA) and the other 7 (5.8%) refused RFA therapy or surgery and underwent alternative treatment and chemotherapy or were lost to follow up. Of stage B patients, 37 (49.3%) underwent transarterial chemoembolization (TACE) and 14 (18.7%) received RFA treatment, while one
Barcelona Clinic Liver Cancer staging, n (%)
A B C D
Table 5.
155
Overall (n = 348)
Malay (n = 71)
Chinese (n = 239)
Indian (n = 38)
120 (34.5) 75 (21.6) 84 (24.1) 69 (19.8)
20 (28.2) 12 (16.9) 20 (28.2) 19 (26.7)
97 (40.6) 55 (23.0) 54 (22.6) 33 (13.8)
3 (7.9) 8 (21.1) 10 (26.3) 17 (44.7)
Barcelona Clinic Liver Cancer (BCLC) staging and treatment Treatments
BCLC staging A (N = 120) B (N = 120) C (N = 84) D (N = 69)
Surgery
TACE
RFA
Systemic chemotherapy
Other/ palliative
41 (34.2) 0 (0) 0 (0) 0 (0)
0 (0) 37 (49.3) 18 (21.4) 0 (0)
72 (60.0) 14 (18.7) 4 (4.8) 0 (0)
0 (0) 1 (1.3) 0 (0) 0 (0)
7 (5.8) 23 (30.7) 62 (73.8) 69 (100)
RFA, radiofrequency ablation; TACE, transarterial chemoembolization.
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underwent systemic chemotherapy and 23 (30.7%) refused further treatment or underwent palliative or alternative therapy. Most patients with stage C disease (62/84, 73.8%) received only palliative or alternative medical treatment. However, 18 (21.4%) patients with stage C underwent TACE and the other 4 (4.8%) underwent RFA. Targeted chemotherapy with sorafenib was prescribed in only 5 (6.0%) patients with stage C HCC. All 69 patients in stage D received palliative and supportive therapy. AFP levels AFP levels varied widely from 0 to >2 ×106 ng/mL, with a median value of 200 ng/mL (25–75% quartiles 18–4000 ng/mL). Exactly half the patients exceeded the arbitrary cut-off level of >200 ng/mL. The range of AFP levels according the BCLC staging are shown in Table 6. The proportion of patients with elevated AFP levels ≥200 ng/mL was significantly higher in stage C and D than in stage A and B (P < 0.001). There were no significant differences in the AFP levels between stages A and B or C and D, respectively. Tumor metastasis Tumor metastasis was noted in 68 (19.5%) patients (Table 7). The lungs were the most common site of metastasis, with solitary or multiple nodules seen in 61 (17.5%) patients, followed by tumor metastasis to Table 6. The range of α-fetoprotein (AFP) levels according the BCLC staging AFP levels (ng/mL)
BCLC stage, n (%)
1000
A (N = 120) B (N = 75) C (N = 84) D (N = 69)
83 (69.2) 47 (62.7) 22 (26.2) 25 (36.2)
16 (13.3) 9 (12.0) 12 (14.3) 10 (14.5)
21 (17.5) 19 (25.3) 50 (59.5) 34 (49.3)
Table 7.
Tumor metastasis (N = 348) n (%)†
Lungs Bone Para vertebral mass Intra-abdominal lymph nodes Adrenal Mediastinal lymph nodes No documented metastasis
61 (17.5) 16 (4.6) 3 (0.9) 32 (9.2) 4 (1.1) 4 (1.1) 280 (80.5)
†Metastasis in more than one location in some patients.
intra-abdominal lymph nodes in 32 (9.2%) and to bone in 16 (4.6%), while metastases to the adrenals (1.1%), paravertebral area (0.9%) and mediastinal lymph nodes (1.1%) were also observed. DISCUSSION Liver cancer is an important cancer in Malaysia that places a huge burden on the country’s health resources. Although it ranks only as the sixth most frequent cancer, HCC is the second most common cancer in the digestive tract following colorectal cancer in Malaysian men.3 The frequency of cancer follows a racial pattern, with the Chinese being affected most, followed by the Malays and Indians, as is shown in our hospital admission prevalence statistics and is confirmed by the National Cancer Registry Database.2,3 We have previously reported and discussed quite extensively the epidemiology of liver cirrhosis in Malaysia.8 The etiological factors in the different racial groups showed an interesting and peculiar pattern, reflecting the different epidemiology of chronic viral hepatitis B and C, alcohol intake and diabetes mellitus among the different races in this country.8 In this study, we have again shown that, similar to liver cirrhosis, among Chinese and Malays HBV infection is the main etiological factor. In contrast, among Indians, alcohol intake and cryptogenic cause accounted for over 50% of the cases. We have discussed previously the peculiar epidemiology of heavy alcohol intake in the country, which appears to be confined to socioeconomically poor Indians presenting with liver cirrhosis.8 HBV infection continues to be the most important cause of chronic liver disease in Malaysia. Despite the introduction of mass vaccination of newborns in 1989 in the country, the reservoir of HBV infection in the middle and elder age adult population remains large and will presumably only start to decline in 2050. Although HCV infection was found in a significant proportion of Malay patients with HCC (18.3%), it is significantly lower in both Indian and Chinese patients. Overall, HCV infection was found in only 10.6% of our HCC cases and is not an important cause of chronic liver disease or HCC in Malaysia. This is in contrast to those reported in the Western countries and Japan, where hepatitis C is a major cause of chronic liver disease and the most frequent cause of HCC.11,12 On the other hand, 16.4% of all HCC patients was cryptogenic. We have shown that most patients in this
© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 152–158 category had a history of long-standing diabetes mellitus and presumably had pre-existing non-alcoholic fatty liver disease. With the increasing incidence of diabetes mellitus13–15 and the high prevalence of fatty liver in our population, and especially among Malays and Indians, as shown in our recent publication,16 the proportion of HCC patients with associated nonalcoholic fatty liver disease and the overall number of HCC cases appear likely to increase dramatically. It is also important to note that Malays constitute up to 60% of our population, showing that the increase in absolute number of cases and the overall health burden in the country would be quite marked. Clinical presentations of our patients are protean. Nearly one-third of our patients were asymptomatic at presentation and were detected incidentally with an abdominal mass on clinical examination, a lesion at ultrasonography or on the detection of elevated AFP level. Only one-quarter of the patients presented with abdominal pain, while a significant proportion (17.0%) presented with abdominal discomfort and distension rather than actual pain. Interestingly, a small but significant proportion of patients (8.3%) presented with only weight loss. Only 18.7% of patients presented with some specific liver-related complaint and 8.6% were detected in patients with already established liver cirrhosis and failure. The early detection of HCC remains the key to a favorable treatment outcome of HCC. The hepatitis B surveillance clinic has been in existence in our hospital since 1984; the original aim being to review and follow up ‘blood bank-screened’ HBV-positive individuals. This clinic has now been expanded for the surveillance of all chronic viral hepatitis patients. AFP levels and ultrasonography of the liver are carried out in patients at regular intervals (usually at 6-monthly intervals). It is disappointing, however, to note that only a small proportion of patients (15.8%) were detected on a surveillance clinic follow up. The rate of HCC detection through surveillance is low among all three races, although it is higher in the Chinese, as the proportion of hepatitis B is higher in this racial group and proportionately more are therefore likely to attend the hepatitis B surveillance clinic follow up. One-third of our patients were staged with BCLC stage A, almost half with stages B and C, and 19.8% were classified as BCLC stage D. Of the three races, it is interesting to note that the proportion of Indian patients presenting with stage D disease was significantly higher than the Malays and Chinese. This can
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be explained by the fact that most Indian patients are poor and seek healthcare at a late stage of disease. It also reflects the predominant underlying etiology of HCC. Many Indian patients with HCC present with decompensated alcoholic cirrhosis and liver cancer is detected only at that point in time. The treatment of HCC reflects the availability of local expertise and resources. Overall, relatively few of our patients underwent curative resection. Of the BCLC stage A patients, only 34.2% of them underwent surgery whereas more than half underwent RFA. Liver transplantation is not established in Malaysia for the treatment of liver cancer and is not available in our medical center. Of the stage B and C patients, onethird underwent TACE, while many patients opted for alternative or mainly supportive therapy. In our local setting both RFA and TACE are frequently used with the availability of a dedicated interventional hepatobiliary radiology team. However, both procedures remain expensive. Since 2008 TACE has been carried out with drug-eluting beads and doxorubicin, which has added to the overall cost of the procedure. This has invariably influenced the choice of treatment of many of our patients, who have opted for various alternative traditional types of therapies which are less expensive. Targeted chemotherapy was only recently introduced in Malaysia in 2009 and, together with the high cost of therapy, has understandably been used in only a minority of patients. To our knowledge, this is a first report on HCC from Malaysia. Our study described the real-life clinical experience of a busy general hospital and although it is a single center study, we feel it reliably reflects the epidemiology, clinical features and treatment approaches to the disease in this country at the current time. Despite the increased awareness of hepatitis B and C among the public and the health profession, a significant proportion of patients present late with the advanced liver cancer. This has restricted their choice of treatment options. The proportion of hepatitis B-related HCC will invariably decline with the effect of mass vaccination on all newborns implemented in the country since 1989. However, at the same time, the increase in diabetes mellitus and the high prevalence of fatty liver disease, especially among the Indians and Malays, is greatly worrying16 and portends a marked increase in chronic liver disease cirrhosis and cancer in Malaysia. The increase in the prevalence of obesity and fatty liver is a global phenomenon. Obesity is already regarded
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as occurring in epidemic proportions in the Asia– Pacific region17 and perhaps a harbinger of an epidemic of HCC in the future.18 REFERENCES 1 World Health Organization International Agency for Cancer Research. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Cited: 29 January 2015. Available from URL: http://globocan.iarc .fr/accessed 2 Lim GCC, Halimah Y, eds. Second Report of the National Cancer Registry. Cancer Incidence in Malaysia 2003. Kuala Lumpur: National Cancer Registry, 2004. 3 Ariffin Z, Nor Saleha IT. National Cancer Registry Report 2007. Ministry of Health, Malaysia, 2011. 4 Goh KL, Cheah PL, Md N, Quek KF, Paraskathi N. Ethnicity and H. pylori as risk factors for gastric cancer in Malaysia: A prospective case control study. Am J Gastroenterol 2007; 102: 40–5. 5 Goh KL, Parasakthi N. The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial South–East Asian country. Eur J Gastroenterol Hepatol 2001; 13: 177–83. 6 Tan TC, Vadivale M, Ong CN. Prevalence of hepatitis B surface antigen and antibody among health care employees in Negri Sembilan, Malaysia, 1989. Asia Pac J Public Health 1992–1993; 6: 134–9. 7 Yap SF. Chronic hepatitis B infection in Malaysians. Malays J Pathol 1994; 16: 3–6. 8 Qua CS, Goh KL. Liver cirrhosis in Malaysia: peculiar epidemiology in a multiracial Asian country. J Gastroenterol Hepatol 2011; 26: 1333–7. 9 Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases.
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