Profile and Risk Factor of Hepatocellular Carcinoma Patients

Siti Hasnita O. Purba

, Imelda Rey

2, 3

Student of Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

Division of Gastroenterohepatology, Internal Medicine Department, Universitas Sumatera Utara, Medan, Indonesia

Adam Malik General Hospital, Bunga Lau Street, Medan, Indonesia

Keywords: Hepatocellular Carcinoma, Profile, Risk Factors.

Abstract: Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor in the world. The

incidence of hepatocellular carcinoma varies worldwide and is correlated with the incidence of hepatitis B

virus and hepatitis C virus. In addition to viral hepatitis, there are other risk factors such as alcohol

consumption that causes alcoholic liver disease and obesity and diabetes associated with non-alcoholic fatty

liver disease (NAFLD) / non-alcoholic steatohepatitis (NASH). Most of these risk factors lead to the

development of liver cirrhosis. One of the most commonly used stages of hepatocellular carcinoma is

Barcelona Clinic Liver Cancer (BCLC) staging system that can also determine which therapy will be given

to patients with hepatocellular carcinoma. The aim of this study was to determine the profile and risk factors

of hepatocellular carcinoma patients. This cross-sectional study using HCC patient’s medical records in

Adam Malik General Hospital from January 2016 – June 2017. There were 182 patients with hepatocellular

carcinoma with the highest age group 40-60 years (54.4%), dominated by male sex (80.2%), occupation

with the highest prevalence is self-employed (27.5%), has no family history (97.8%), risk factors with the

highest prevalence is hepatitis B (47.3%), Child-Pugh B (57.1%), multinodular radiology (51.1%), AFP

increased, BCLC stage B (40.7%) and treated with symptomatic treatment (78%). The highest risk factor in

patients with hepatocellular carcinoma is hepatitis B.

1 INTRODUCTION

Hepatocellular carcinoma (HCC) is a primary

malignant liver tumor that originating from

hepatocytes (Budihusodo, 2014). HCC is the ninth

most common cancer in women and fifth in men.

HCC mortality rate is also very high, in second place

of cancer-related death after lung cancer

(GLOBOCAN 2012).

The incidence of HCC varies worldwide and

correlates with regional prevalence of Hepatitis B

Virus (HBV) and Hepatitis C Virus (HCV)

(Budihusodo, 2014). In the endemic areas, HBV is

majority obtained by vertical and perinatal

transmission more than 90% of these cases changes

to chronic HBV carriers. HBV is a well-known

cause of HCC because it can become HCC without

cirrhosis, although most HBV (70-90%) develop

into cirrhosis prior to becoming HCC (Yang et al,

2011). Some cases of HCV has been reported, in

Italy 44-66% turn in to HCC cases and about 80% in

Japan. Whereas, in United States, the chronic HCV

was also a major risk factor for HCC (El-Serag,

2007).

Other risk factors of viral hepatitis, such as

alcohol consumption that associated to alcoholic

liver disease and obesity and diabetes associated

with non-alcoholic fatty liver disease (NAFLD) /

non-alcoholic steatohepatitis (NASH). Most of these

risk factors lead to the development of liver cirrhosis

present in 80-90% of HCC patients (El-Serag, 2011).

Several studies reported that risk of developing HCC

through NASH-associated cirrhosis is lower than

other liver diseases, such as HCV and HBV

(Takuma, 2010).

Although the prevalence of HCC in patients with

NASH is low, but the prevalence of obesity-related

NASH in the United States is high and it is a leading

to indicated a major causes for liver transplantation

(Wong, 2014).

Purba, S. and Rey, I.

Proﬁle and Risk Factor of Hepatocellular Carcinoma Patients.

DOI: 10.5220/0010070204250428

In Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches (ICOSTEERR 2018) - Research in Industry 4.0, pages

425-428

ISBN: 978-989-758-449-7

425

2 METHODS

This study was a cross-sectional study design. Data

were taken by using secondary data from medical

record of hepatocellular carcinoma patients at RSUP

Haji Adam Malik Medan period 1

of January 2016

until 30

of June 2017. The sampling method was

done by total sampling method. Data taken include

age, sex, risk factors, laboratory results, child-pugh

classification, radiological results, BCLC stage,

tumor marker results and therapy provided.

3 RESULT

This study was obtained 182 patients hepatocellular

carcinoma who visited the RSUP Haji Adam Malik

Medan during the period 01 January 2016 - 30 June

2017.

Table 1 : Characteristics of HCC patients

Characteristic n = 182

Sex

Men

Women

146 (80,2)

36 (19,8)

Age (years)

< 40

40-60

> 60

25 (13,7)

99 (54,4)

58 (31,9)

Occupation

Government

employees

Private employees

Entrepreneur

Farmers

Housewife

Retired

Others

18 (9,9)

19 (10,4)

50 (27,5)

39 (21,4)

17 (9,3)

22 (12,1)

Risk factors

HBV

HCV

Cirrhosis

Alcohol

Diabetes

Obesity

86 (47,3)

10 (5,5)

60 (33)

41 (22,5)

16 (8,8)

29 (15,9)

Laboratory data

Hb (g/dL)

Leucocyte

10,9±2,7

10.705,13±4957,31

(cells/mm

)

Trombosite

(thousand/mm

)

ALT (U/L)

ASP (U/L)

ALP (U/L)

Gamma-GT (U/L)

Bilirubin (mg/dL)

Albumin (g/dL)

INR

275.756,90±1,60

69,81±76,09

201,65±252,12

277,18±265,64

345,88±305,02

3,8±6,4

2,7±0,65

1,2±0,39

Tumor marker

AFP (ng/ml)

CEA (ng/ml)

CA125 (u/ml)

CA19-9 (u/ml)

26.728,84±1,67

464,33±1856,02

286,26±261,67

161,09±351,64

Child-Pugh score (%)

Missing

47 (25,8)

104 (57,1)

27 (14,8)

4 (2,2)

Tumor type (%)

Soliter

Multinoduler

Diffuse

Missing

52 (28,6)

93(51,1)

7 (3,8)

30 (16,5)

BCLC stage (%)

Missing

14 (7,7)

30 (16,5)

74 (40,7)

13 (7,1)

25 (13,7)

26 (14,3)

Treatment (%)

Hepatic resection

TACE

Liver transplantation

Symptomatic

2 (1,1)

37 (20,3)

142 (78)

1 (0,5)

4 DISCUSSION

Table 1 shows the characteristics of patients in

which the largest number of hepatocellular

carcinoma patients were men. This is in accordance

with previous study that found the most sex in

hepatocellular carcinoma patients were male

(Karageorgos et al, 2017; Mittal et al, 2015). Sex

influences are also associated to sex hormones

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

426

namely androgens and estrogens which is main

regulated the progression of HBV infection and the

incidence of HBV-associated to hepatocellular

carcinoma, in which androgens increase the

transcription and replication of the HBV gene

whereas the estrogen plays a protective role by

decreasing the transcription of HBV RNA and the

number of inflammatory cytokines (Montella, 2015).

In addition, high alcohol consumption in men also

increases the hepatocellular carcinoma incidence

risk in people that infected by hepatitis B and

hepatitis C virus (Budihusodo, 2014).

The most risk factor in hepatocellular carcinoma

patients in this study is hepatitis B. Chronic hepatitis

B infection was a major risk factor for hepatocellular

carcinoma in the world (El-Serag, 2011). About 80%

of the world's hepatocellular carcinoma cases are in

developing countries such as East Asia and

Southeast Asia and Central Africa, which is known

to be a high prevalence of viral hepatitis

(Budihusodo, 2014).

Chronic hepatitis B can progress to

hepatocellular carcinoma without cirrhosis, although

most develop into cirrhosis before it becomes

hepatocellular carcinoma (Yang et al, 2011). In this

study, the second highest risk factor was cirrhosis

hepatis. This is associated with high incidence of

hepatitis B and other risk factors that can develop

into cirrhosis before becoming hepatocellular

carcinoma.

The laboratory results of hepatocellular

carcinoma patients where the mean Hb decreases,

normal leukocytes, normal platelets, ALT increases,

ASP increases, ALP increases, Gamma-GT

increases, bilirubin increases, normal albumin and

normal INR. The most common abnormalities in

liver tumors are elevated alkaline phosphatase

(ALP) and GT gamma. The concentrations of SGOT

/ AST and SGPT / ALT enzymes in hepatocellular

carcinoma at baseline did not show an increase

unless the underlying disease was cirrhosis of the

liver. When the tumor gets bigger and greater liver

damage can also be found an increase in AST and

ALT (Amirudin, 2014).

In the results of tumor marker examination of

hepatocellular carcinoma patients found the average

AFP increased, the average CEA increased, the

average CA125 increased, and the average CA19-9

increased. AFP is a specific tumor marker in

diagnosing hepatocellular carcinoma, whereas other

tumor markers such as CEA, CA125 and CA19-9

are not specific but may increase with worsening

disease (Li et al, 2015).

In Asia, hepatocellular carcinomas usually

appear as well-described, solitary or multifocal

masses and are associated with secondary cirrhosis

due to hepatitis B. In western countries,

hepatocellular carcinomas usually appear as diffuse

infiltration masses and are associated with alcohol-

induced cirrhosis (Sharma, 2009). In this study, the

most radiology results in patients with hepatocellular

carcinoma multinodular. It is accordance with the

previous study that get the most tumor type is

multinodular (Su et al, 2017) .

The most common of Child-Pugh classification

in hepatocellular carcinoma patients was Child-Pugh

B. This study is in accordance with the previous

study which received the most Child-Pugh

classification is Child-Pugh B (Nadhim, 2016). The

most BCLC staging in patients with hepatocellular

carcinoma is stage B. According to previous study, it

showed that the highest stage of BCLC in

hepatocellular carcinoma hepatitis B virus etiology

is stage B (Nadhim, 2016). While in another study

received the highest stage BCLC was stage C (Mittal

et al, 2015; Hidayat, 2007). BCLC staging is closely

related to the Child-Pugh classification and

radiology results in patients, where in this study the

most Child-Pugh classifications are Child-Pugh B

and multinodular radiology results. That all

determine the choice of therapy which in this study

the most common treatment to the patients with

hepatocellular carcinoma is symptomatic treatment.

5 CONCLUSION

Most of patients were in BCLC staging B , with the

highest risk factor in patients with hepatocellular

carcinoma is hepatitis B.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge that the present

research is supported by Ministry of Research and

Technology and Higher Education Republic of

Indonesia.

REFERENCES

Amirudin, R. 2014, ‘Fisiologi dan Biokimia Hati’, in

Setiati, S. et al. (eds) Buku Ajar Ilmu Penyakit Dalam

Jilid II. Interna Publishing. Jakarta, 6

Edition.

Budihusodo, U. 2014, ‘Karsinoma Hati’, in Setiati, S. et

Proﬁle and Risk Factor of Hepatocellular Carcinoma Patients

427

al. (eds) Buku Ajar Ilmu Penyakit Dalam Jilid III.

Interna Publishing. Jakarta, 6

Edition.

El–Serag, H. B., & Rudolph, K. L. 2007. Hepatocellular

carcinoma: epidemiology and molecular

carcinogenesis. Gastroenterology, 132(7), 2557-2576.

El-Serag, H. B. 2011, ‘Hepatocellular carcinoma’, The

New England Jorunal of Medicine, 365, pp. 1118–

1127.

Hidayat, H. 2007. Perbedaan profil klinik karsinoma

hepatoseluler yang terinfeksi kronik virus hepatitis B

dengan virus hepatitis C (Doctoral dissertation,

FacultyofMedicine).Availableat:http://eprints.undip.ac

.id/22680/1/Hendri_Hidayat.pdf

International Agency of Research on Cancer 2012,

GLOBOCAN 2012: Estimated Cancer Incidence,

Mortality and Prevalence Worlwide in 2012.

Available at:

http://globocan.iarc.fr/Pages/fact_sheets_population.as

px.

Karageorgos, S. A., Stratakou, S., Koulentaki, M.,

Voumvouraki, A., Mantaka, A., Samonakis, D., et al.

2017. Long-term change in incidence and risk factors

of cirrhosis and hepatocellular carcinoma in Crete,

Greece: a 25-year study. Annals of

gastroenterology, 30(3), 357.

Li, Y., Li, D. J., Chen, J., Liu, W., Li, J. W., Jiang, P., et

al. 2015. Application of Joint Detection of AFP,

CA19-9, CA125 and CEA in Identification and

Diagnosis of Cholangiocarcinoma. Asian pac J Cancer

prev, 16, 3451-3455.

Mittal, S., Sada, Y. H., El-Serag, H. B., Kanwal, F., Duan,

Z., Temple, S., et al. 2015. Temporal trends of

nonalcoholic fatty liver disease–related hepatocellular

carcinoma in the veteran affairs population. Clinical

Gastroenterology and Hepatology, 13(3), 594-601.

Montella, M., D’Arena, G., Crispo, A., Capunzo, M.,

Nocerino, F., Grimaldi, M., et al. 2015. Role of sex

hormones in the development and progression of

hepatitis B virus-associated hepatocellular

carcinoma. International journal of

endocrinology, 2015.

Nadhim, M., Suharti, C., Hardian. 2016. 'Distribusi

Geografis dan Tingkat Keparahan Pasien Karsinoma

Hepatoseluler Etiologi Virus Hepatiis B di RS Kariadi

Semarang', Jurnal Kedokteran Diponegoro, 5(4),

pp.1290-1302.

Sharma, R. and Madhusudhan, K. S. 2009, ‘Malignant

Focal Lesions of The Liver’, in Gupta, A. K.,

Chowdhury, V., and Khandelwal, N. (eds) Diagnostic

Radiology Gastrointestinal and Hepatobiliary

Imaging. Jaypee. New Delhi, 3

Edition.

Su, Y. W., Liu, P. H., Hsu, C. Y., Lee, Y. H., Hsia, C. Y.,

Ho, S. Y., et al. 2017. Prognostic impact of diabetes

mellitus on hepatocellular carcinoma: Special

emphasis from the BCLC perspective. PloS

one, 12(3), e0174333.

Takuma, Y., & Nouso, K. 2010. Nonalcoholic

steatohepatitis-associated hepatocellular carcinoma:

our case series and literature review. World journal of

gastroenterology: WJG, 16(12), 1436.

Wong, R. J., Cheung, R., & Ahmed, A. 2014.

Nonalcoholic steatohepatitis is the most rapidly

growing indication for liver transplantation in patients

with hepatocellular carcinoma in the

US. Hepatology, 59(6), 2188-2195.

Yang, J. D., Kim, W. R., Coelho, R., Mettler, T. A.,

Benson, J. T., Sanderson, S. O., et al. 2011. Cirrhosis

is present in most patients with hepatitis B and

hepatocellular carcinoma. Clinical Gastroenterology

and Hepatology, 9(1), 64-70.

ICOSTEERR 2018 - International Conference of Science, Technology, Engineering, Environmental and Ramiﬁcation Researches

428