**6. Treatment options for HCC**

infected with the other genotype strains. Furthermore, those patients respond poorly to cur-

HCV infection is also one of the frequent risk factors in developing HCC in the word. The risk of HCC is very high in patients chronically infected with HCV [19]. Coinfection with HIV or HBV increased this risk further. The high majority of coinfected patients with either HIV or HBV precipitate chronic hepatitis, leading to HCC. Suppression of HCV load by IFN therapy, apparently, participates in reducing the onset of HCC [20]. However, concerns regarding the impact of HCV direct-acting agents (DAAs) on the incidence of HCC continue to be raised in clinic [21]. The potential increased risk of HCC in HCV patients under DAAs therapy has been reported [22]. Therefore, interferon therapy should not be discontinued at

Evidence shows that long-term alcohol use is responsible for alcoholic liver disease (ALD) and a high risk of developing HCC [23]. ALD is well characterized; however, little progress has been made for its treatment. It is well established that alcohol is highly toxic to hepatocytes. By causing continuous cell necrosis, it induces perpetual regeneration of hepatocytes and paves the way to carcinogenesis [24]. In addition, alcohol causes liver damage by promoting inflammation that precipitates cirrhosis and leads to HCC [23]. The effect of alcohol on liver

NASH is a condition of fatty liver disease in which liver has abnormal fat accumulation and increased inflammation. Although the exact etiology of NASH remains unknown, the risk factors include obesity, type II diabetes, and related metabolic dysfunctions. NASH patients with no cirrhosis have no increased risk of HCC, indicating that induction of liver cirrhosis is a leading cause of HCC. However, the outcome of NASH is much similar as other chronic hepatitis such as HCV infection [26]. Although the risk of developing HCC might be lower in NASH patients than HCV patients, the severity of HCC and patient survival in both cases

The majority of HCCs arise from liver cirrhosis, a condition in which liver tissue is replaced by scar tissue [27]. The scar tissue jeopardizes the blood flow through the liver and retains it from functioning correctly. Cirrhosis results mainly from different chronic hepatitis mainly due to viral infections and fatty liver disease related or unrelated to alcohol abuse. Currently, besides HBV, HCV, and HDV, three hepatitis viruses are identified and have been demonstrated to

rent therapies based on interferon or other antiviral agents [15, 16].

**4.2. Hepatitis C virus (HCV) infection**

least for HCV patients with high risk of HCC.

disease is boosted in people with viral hepatitis [25].

**5. Liver cirrhosis and other risk factors for HCC**

**4.4. Nonalcoholic steatohepatitis (NASH)**

**4.3. Alcohol abuse**

6 Liver Cancer

remain similar.

Currently, many options are available for the treatment of HCC [30]. Potentially curative treatments like surgical resection or liver transplantation might be possible for less advanced HCC. Minimally invasive surgical technologies continue to improve increasing its safety and applicability for oncologic liver surgery. Different surgical procedures, including advanced surgical technologies, are currently performed.

Unfortunately, tumor recurrence and metastasis frequently occur after resection and limit the overall survival. In patients with unresectable HCC and preserved liver function, transarterial chemoembolization (TACE) can prolong survival. However, TACE is rarely curative. More than half of patients with HCC continue to die secondary to liver failure from progressing cirrhosis. Current chemotherapy, interferon treatment, or alternative medicine only partially benefits patients with advanced disease. Therefore, novel treatments for liver cancer, particularly advanced HCC, are in urgent need [31].

Since the introduction of sorafenib, a multikinase inhibitor that showed some benefits to HCC patients, other targeted and immune therapies emerged for the treatment of HCC. Currently, promising therapies for HCC are underway, including targeted therapy, immune checkpoint inhibitors, oncolytic viruses (OVs), and chimeric antigen receptor-redirected T cells (CAR-T cells). Combination strategies are also under investigation to promote further the treatment of advanced HCC [32].
