Characteristics of Hepatocellular ‎Carcinoma in Egyptian Patients : ‎A Single Center Pilot Study ‎

• Hepatocellular‏ ‏Carcinoma is one of the most widespread leading causes of mortality.
• The most frequent risk factors for HCC are chronic HBV and HCV infection, which ‎account for 80% of all HCC cases globally.

One of the highest incidences of all hepatic malignancies is  hepatocellular carcinoma [18]. It often arises in cirrhotic livers with serious complications [19]. Recent efforts have been made to change the reality of poor prognosis and short survival times [20-22]. Options for treatment mostly depend on the stage of the HCC tumor.

In this study, males were more predominantly exposed to HCC (68%) than females (32%) with a ratio about (2.1:1). This in accordance with previous results of Hossain et al. [23]; Guyton et al. [24]; Yang et al. [25]; Huang et al. [26] Ganong et al.[27];Graevfore et al. [28], this can be explained by the delayed development of HCC in females and in some racial groups, which support the hypothesis of a protective effect of female sex hormones against HCC development.

In this work, incidence of HCC was increased in patients more than 50 years ,  this also reported by El-Serag et al.  [29] who reported that older male patients had increased HCC incidence in cirrhotic individuals.

Other studies support our results such as;  Hossain et al.  [23] who found that patients between 41 and 50 years were the most commonly exposed to HCC, this can be explained by long standing chronic viral hepatitis all over years and accumulated  risk factors with age  such as ;liver cirrhosis

In accordance with results of Hashem et al. [30] who demonstrated increased HCC incidence among older HCV infected patients due to long standing established risk factors like HCV and liver cirrhosis.

Also, Dohmen et al. [31] reported that   increased incidence may be linked to increased life expectancy, which increases the incidence of HCC development in older patients 

In this work, there was high incidence of HCC among child A patients than child B & C.

The only possible explanation for these findings was the strict early screening program for detection of HCC in our tertiary center, which allows early detection of small lesions, unlike what is expected, advanced cirrhosis may not be linked to a high incidence of HCC

AFP (alfa feto protein) is a protein made in the liver of a developing baby and healthy adults should have very low levels of AFP.

AFP synthesis is suppressed in adults. Only during pregnancy, in specific tumours (such as HCC, gastric carcinoma, lung cancer, pancreatic cancer, and testicular carcinoma), and in non-tumor situations (such as chronic hepatitis and liver cirrhosis) are elevated AFP serum levels observed in the maternal serum.  [32]

When the cut-off value is 20 ng/ml, serum AFP has a sensitivity of 41–65% (so it may be false negative) and a specificity of 80–94%.

However, AFP levels more than 400 g/L are typically regarded as diagnostic of HCC [33] A recent meta-analysis on the effectiveness of AFP in the diagnosis of HCC included seven studies and indicated a pooled sensitivity of 66% with a specificity of 86%. [33, 34]

At the time of tumour diagnosis, AFP appears to have prognostic value. Patients with HCC who have high AFP concentrations (400 ng/mL) have larger tumours, bilobar involvement, portal vein invasion, and a worse median survival rate.[35]

Patients with blood AFP levels greater than 1000 ng/ml have a higher frequency of vascular invasion (61% versus 32%). [36]

Our results demonstrated that 26.3% of patients with HCC had normal AFP level, 83.8% had AFP < 400 ng/dl and only 16.2 % had AFP more than 400 ng/dl.

These surprising results may be due to the fact that some types of HCC may not secrete AFP i.e.; fibrolamellar HCC [37].

Furthermore,  in AFP-producing HCC, AFP can also be employed as a marker to identify tumour progression. If the pre-treatment increased AFP levels drop to and stay at normal levels during future follow-up measurements after the tumour has been treated, a full response is anticipated[38].

There was 26.3% had normal AFP level (below 10  ng/mL) which will be  missed in diagnosis if we depended on  AFP level  only , so we finally reported that, no diagnostic AFP cut off level for HCC diagnosis, because patients with HCC may have normal titer of AFP, and diagnosis doesn’t  depends only on AFP alone but radiology is mandatory.

One of our interesting findings that, the majority of patients with HCC were not received any lines of treatment for HCV infection, while small portion of patients who received different modalities of therapy developed HCC, this may be due to the effect of HCV particles and liver cirrhosis induced by HCV infection and comorbidities: DM and Insulin Resistance [39], [40 ], [41].

Our results are supported by previous findings of; El-Zayadi et al. [42]; Shi J et al. [43].  These findings  explained by that  HCV is the major risk factor of HCC in cirrhotic patients.

In addition to that, treatment of HCV may be a protective factor against HCC development in accordance with Marrero et al. [44]; Griffith et al. [45]; who demonstrated that successful DAA therapy is associated with a 71% reduction in  HCC risk.

This can be explained by eliminated HCV particles by DAA treatment which activate CD8+ T cells to respond to the HCV also induces a T-cell mediated response and increased immune surveillance to the virus-induced aggressive HCC tumor and also due to decreased liver fibrosis after HCV treatment.

In our study, there were (39.7%) diabetic  patients  with HCC, this can be explained by; One possible mechanism of carcinogenesis

suggested that patients with non insulin dependent diabetes mellitus are characterized by insulin resistance, compensatory hyper-insulinemia and increased growth factor production  [46]^.

It is believed that hyperinsulinemia and hyperglycemia directly stimulate hepatic stellate cells, leading to activation of connective tissue growth factor and subsequent accumulation of extra­cellular matrix [47]. Although insulin can directly induce tumour growth, many of its mitogenic and antiapoptotic effects are operating through the (Insulin like growth factor)IGFI system, in particular breast and prostate cancers, have been documented ^.[48].

With regard to incidence of HCC in diabetic patients, widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non-cirrhotic livers in about 40% of cases.

CONCLUSION

Hepatocellular carcinoma is predominant in older male patients ‎with chronic hepatitis C who are not receiving any modalities of ‎treatment  and  have diabetes mellitus‎‎.

ACKNOWLEDGMENT

The authors would thank all of their colleagues who helped conduct this study. We are also grateful to Dr. Mohammed Elegezy, associate professor of Tropical medicine, Faculty of ‎Medicine, Mansoura University, Mansoura, Egypt for reviewing this article.‎

Funding: None.

Conflict of interest: None

Ethical consideration:

Prior to the study's execution, the Ethical Committee of Mansoura University's Faculty of Medicine gave its approval (IRB no. MS. 21.02.1386).