The Rising Threat of Hepatocellular Carcinoma in the Middle East and North Africa Region: Results From Global Burden of Disease Study 2017

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Abbreviations

ALD

alcoholic liver disease

ASIR

age‐standardized incidence rate

ASMR

age‐standardized mortality rate

GBD

Global Burden of Disease

HBV

hepatitis B virus

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

MENA

Middle East and North Africa

NASH

nonalcoholic steatohepatitis

UAE

United Arab Emirates

Background

Hepatocellular carcinoma (HCC) is the most common neoplasm of the liver. It is mostly found as the outcome of chronic liver diseases, such as hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD).1 Liver cancer, with an incidence of 1.0 million in 2016, ranked as the seventh most common cancer globally. Liver cancer ranked as the fourth deadliest cancer globally, with 829,000 deaths in 2016.2 The overall survival of patients with HCC in the absence of treatment is very short, as found by a study in the United States, with a median survival time of 3.6 months.3 The current therapies for HCC, such as transarterial chemoembolization, can improve the overall survival of patients with HCC; however, long‐term complete remission is a rare event, especially in those with advanced stage HCC.4, 5 Despite the fact that patients with HCC have ill‐fated outcomes, the risk for HCC development and the incidence rate of HCC would be easily reduced with prevention and/or optimal management of HCC's underlying diseases, especially HBV infection, HCV infection, NASH, and ALD.6, 7, 8 The Middle East and North Africa (MENA) region, with a high prevalence of viral hepatitis, especially HCV infection, and lack of appropriate preventive and therapeutic interventions, has a rising burden of HCC. This study aimed to discuss the burden of liver cancer in the MENA region based on the data available from the Institute for Health Metrics and Evaluation Global Burden of Disease Study 2017 (GBD 2017).9

Methods

The data of liver cancer incidence, mortality, and contribution of underlying liver diseases in 1990 and 2017 in 21 MENA countries (Table 1) were extracted from the GBD Results Tool.9 The data of GBD for liver cancer include all primary liver neoplasms. The source of the data presented by GBD is a range of scientific literature (articles), vital, death, cancer, and other registries.10 The age‐standardized incidence rate (ASIR) and age‐standardized mortality rate (ASMR) of liver cancer were extracted and presented directly from the GBD Results Tool. The contribution of underlying diseases to liver cancer incidence and the change in the ASIR of liver cancer, including the results for each of the underlying diseases, were calculated using the data extracted from GBD Results Tool. These results were presented as appropriate for each MENA country to show the change in burden of liver cancer and the contribution of underlying liver diseases in 1990 and 2017.

Table 1.

Liver Cancer Incidence Rate, Mortality Rate, and Underlying Diseases in MENA Countries in 1990 and 2017

Country	Incidence Rate of Liver Cancer*		Mortality Rate Due to Liver Cancer†		Contribution of Underlying Disease in Liver Cancer Incidence in 1990 (%)					Contribution of Underlying Disease in Liver Cancer Incidence in 2017 (%)
	1990	2017	1990	2017	HBV	HCV	NASH	ALD	Other‡	HBV	HCV	NASH	ALD	Other‡
Afghanistan	6.50	5.74	6.73	5.95	34.42	35.76	8.83	10.98	10.02	37.44	32.77	8.79	9.31	11.69
Algeria	1.62	2.00	1.73	2.14	33.82	36.55	8.70	11.08	9.85	30.15	38.31	11.27	11.60	8.67
Bahrain	3.78	2.86	4.09	3.12	34.00	35.32	9.68	12.17	8.83	32.92	35.07	11.84	11.85	8.32
Egypt	13.49	19.93	13.79	20.47	16.50	57.75	7.12	9.99	8.64	14.28	58.45	9.17	10.26	7.83
Iran	2.96	3.61	3.16	3.91	40.84	24.57	15.03	7.38	12.18	34.65	27.78	19.74	7.50	10.33
Iraq	4.47	3.24	4.70	3.44	35.18	34.01	10.23	10.37	10.21	33.40	35.05	11.09	10.64	9.82
Jordan	2.34	2.52	2.45	2.76	37.82	32.01	9.43	10.50	10.24	31.36	35.28	12.88	11.77	8.71
Kuwait	3.53	3.97	3.72	4.26	38.86	30.92	10.03	11.43	8.76	31.86	34.58	13.87	11.76	7.93
Lebanon	3.47	3.22	3.58	3.17	42.97	23.62	7.66	17.08	8.66	40.97	23.69	9.99	17.16	8.19
Libya	5.23	5.88	5.45	6.14	35.08	34.27	10.44	10.18	10.03	33.33	34.19	12.93	10.04	9.51
Morocco	1.60	1.74	1.73	1.89	32.33	37.79	9.33	11.53	9.03	29.07	38.92	11.84	11.90	8.27
Oman	4.73	4.37	4.91	4.56	39.33	32.11	7.97	11.65	8.94	37.28	30.88	11.53	11.78	8.54
Palestine	6.09	5.42	6.47	5.86	32.75	37.25	9.91	9.02	11.07	30.91	37.80	11.48	9.78	10.02
Qatar	13.17	8.72	14.43	9.42	34.26	34.06	11.74	11.75	8.19	33.90	33.02	12.77	12.57	7.74
Saudi Arabia	6.36	6.42	6.68	7.01	39.06	38.21	8.60	7.33	6.79	34.78	39.50	11.84	7.25	6.63
Sudan	3.63	3.35	3.87	3.60	31.38	29.57	11.33	15.22	12.49	28.76	29.50	13.65	15.97	12.12
Syria	4.01	3.61	4.23	3.85	36.01	34.26	9.35	9.90	10.49	31.76	36.13	11.69	11.08	9.33
Tunisia	1.66	1.72	1.72	1.79	29.93	45.22	7.79	9.67	7.40	24.78	48.91	9.68	10.19	6.44
Turkey	4.20	3.73	4.37	3.92	44.16	24.18	8.13	13.89	9.64	40.05	25.30	10.42	15.74	8.49
UAE	4.48	5.72	4.71	6.00	43.01	27.00	8.04	12.93	9.01	41.91	27.30	9.94	12.78	8.07
Yemen	3.12	2.97	3.29	3.16	35.11	39.12	8.07	5.53	12.17	32.56	40.49	9.47	5.76	11.72
MENA	5.12	5.73	5.31	5.94	28.85	42.43	8.64	10.62	9.47	24.52	45.17	10.94	10.84	8.54

^*ASIR per 100,000 individuals.

^†ASMR per 100,000 individuals.

^‡Liver cancer due to other causes.

Results

Liver Cancer Incidence Rate, Mortality Rate, and Underlying Diseases

The highest ASIR of liver cancer was observed in Egypt, followed by Qatar, in both 1990 and 2017 (Table 1). The highest ASMR of liver cancer in 1990 and 2017 was observed in Qatar and Egypt, respectively (Table 1). The ASIR of liver cancer in MENA increased by 11.91% from 1990 to 2017 (Table 1). The ASIR of liver cancer increased in Egypt (+47.74%), United Arab Emirates (UAE) (+27.68%), Algeria (+23.46%), Iran (+21.96%), Kuwait (+12.46%), Libya (+12.43%), Morocco (+8.75%), Jordan (+7.69%), Tunisia (+3.61%), and Saudi Arabia (+0.94%), whereas it declined in Yemen (−4.81%), Lebanon (−7.20%), Oman (−7.61), Sudan (−7.71), Syria (−9.98%), Palestine (−11.00%), Turkey (−11.19%), Afghanistan (−11.69%), Bahrain (−24.34%), Iraq (−27.52%), and Qatar (−33.79%) from 1990 to 2017 (Table 1).

In 1990 and 2017, HCV infection was the main etiology for liver cancer in MENA, followed by HBV. Together, they accounted for approximately 70% of all liver cancers in MENA (Table 1). In 1990, the main underlying liver disease for liver cancer was HCV infection in Afghanistan, Algeria, Bahrain, Egypt, Morocco, Palestine, Tunisia, and Yemen, and HBV infection in Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Saudi Arabia, Sudan, Syria, Turkey, and UAE (Table 1). In 2017, the main underlying liver disease for liver cancer was HCV infection in Algeria, Bahrain, Egypt, Iraq, Jordan, Kuwait, Libya, Morocco, Palestine, Saudi Arabia, Sudan, Syria, Tunisia, and Yemen, and HBV infection in Afghanistan, Iran, Lebanon, Oman, Qatar, Turkey, and UAE (Table 1).

HBV‐Related Liver Cancer

The ASIR of HBV‐related liver cancer was decreased (−2.8%) in MENA from 1990 to 2017. The ASIR of HBV‐related liver cancer was decreased in most MENA countries with the exception of Algeria, Egypt, Iran, Libya, and UAE. The highest increase in ASIR of HBV‐related liver cancer from 1990 to 2017 was observed in Egypt (+31.0%), and the highest decrease was observed in Qatar (−36.0%; Fig. 1A).

Figure 1.

The change in the ASIR of liver cancer in MENA countries from 1990 to 2017. (A) HBV‐related liver cancer. (B) HCV‐related liver cancer. (C) NASH‐related liver cancer. (D) ALD‐related liver cancer.

HCV‐Related Liver Cancer

The ASIR of HCV‐related liver cancer was increased (+16.1%) in MENA from 1990 to 2017. The highest increase in ASIR of HCV‐related liver cancer from 1990 to 2017 was observed in Egypt (+47.1%), and the highest decrease was observed in Qatar (−35.6%; Fig. 1B).

NASH‐Related Liver Cancer

From 1990 to 2017, the ASIR of NASH‐related liver cancer was increased (+39.2%) in MENA countries with the exception Afghanistan, Bahrain, Iraq, and Qatar. The highest increase in ASIR of NASH‐related liver cancer from 1990 to 2017 was observed in Egypt (+89.8%), and the highest decrease was observed in Qatar (−27.4%; Fig. 1C).

ALD‐Related Liver Cancer

The ASIR of ALD‐related liver cancer was increased (+12.5%) in MENA from 1990 to 2017. The highest increase was observed in Egypt (+47.9%), and the highest decrease was observed in Bahrain (−30.0%; Fig. 1D).

Discussion

The increasing trends of HCC incidence and mortality rates from 1990 to 2017 in MENA are concerning. The main cause of HCC in MENA has been chronic viral hepatitis; however, the dramatic increase in the absolute number and incidence rate of NASH‐related HCC reveals the change in causative factor of HCC from chronic viral liver diseases to nonviral liver diseases in the near future. Chronic HBV and HCV infections have been found to be the causative agents of 70% of cases diagnosed with HCC in MENA. Hepatitis C has been the main cause of liver diseases in MENA, with a high prevalence rate (>1%) of viremia in the general population of countries such as Egypt (6.3%), Syria (3.0%), Qatar (1.6%), UAE (1.3%), and Bahrain (1.2%).11 The incidence rate of HCV‐related HCC increased (+16.1%) from 1990 to 2017, which calls for more serious interventions from MENA countries. HCV antiviral therapy using direct‐acting antiviral agents is available in most MENA countries.12 Egypt and Qatar are the pioneer countries on track to achieving the elimination of hepatitis C by 2030 in the MENA region.13, 14 State‐funded screening and antiviral therapy of hepatitis C in Qatar have resulted in the diagnosis of 4,400 cases between 2010 and 2016.15, 16 In the past 3 years, Egypt treated more than 2 million patients with HCV infection and in July 2018, it started an HCV mass screening campaign that will find 2.5 to 3 million patients with undiagnosed HCV infection.17

More commitment from other MENA countries to the funding and development of initiatives for testing and treating patients with hepatitis C is needed. This would control the transmission of HCV in groups with high‐risk behaviors, and it would decrease the burden of HCV‐related liver diseases, such as decompensated cirrhosis and HCC in patients with HCV infection.18, 19 The ASIR of HBV‐related HCC in MENA decreased (−2.8%) from 1990 to 2017 (Fig. 1); however, HBV infection remains the second common cause of HCC in MENA thus far. Hepatitis B vaccination, prevention of mother‐to‐child transmission of HBV, and HBV antiviral therapy can significantly reduce the burden of hepatitis B‐related liver diseases.6, 7 In most MENA countries, the coverage of three‐dose vaccination before age 1 year is greater than 90%; however, administration of hepatitis B immunoglobulin and HBV antiviral therapy for high‐viremia mothers has not yet been well implemented in most MENA countries.20 Moreover, the overall rate of diagnosis of hepatitis B surface antigen‐positive individuals (6%) and treatment of eligible patients with HBV infection (2%) are very low in the MENA region, and there is a need for more interventions to increase the diagnosis and improve the access of these patients to antiviral regimens.20

Among all types of HCC, NASH‐related HCC had the highest ASIR increase (+39.2%) in MENA countries from 1990 to 2017. NASH was found to be the fastest growing causative factor for HCC in liver transplant candidates in the United States as well.21 This increasing trend of NASH‐related liver diseases underlies the need for surveillance of noncommunicable diseases globally.

Although the results of the current study based on the GBD 2017 data show the increasing trend of HCC incidence and mortality in MENA countries, the country‐level results should be interpreted carefully. The main concern with these results, including the decrease in burden of HCC in countries such as Iraq and Afghanistan, and the increase in burden of HCC in countries such as UAE and Iran, can be partly attributed to the change and/or improvement in national vital, death, and cancer registries in each country. The current study represents the need for prompt implementation of preventive and therapeutic interventions for chronic liver diseases in MENA countries considering the most contributing HCC underlying diseases for each country.