Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Effectiveness of combined therapy radiofrequency ablation/transarterial chemoembolization versus transarterial chemoembolization/radiofrequency ablation on management of hepatocellular carcinoma.

BACKGROUND: One of the most widespread cancer-associated death worldwide is Hepatocellular carcinoma. Concerning hepatic malignant tumor staging system known as Barcelona clinic of liver cancer, a superior curative response could be carried out by combined techniques [radiofrequency ablation (RFA) and transarterial chemoembolization (TACE)] for stage B comparing with TACE alone as palliative monotherapy. OBJECTIVES: To discuss the merging effect of RFA followed by TACE and vice versa on objective response, overall survival, local recurrence and tumor-free survival. PATIENTS AND METHODS: Sixty-eight cases included with hepatic tumor on top of chronic liver disease post-viral infection and divided into two groups according to different combined treatment modality; first cohort included 34 patients treated with TACE followed by RFA, while the second one included 34 patients treated with RFA followed by TACE for two lesions or single medium-sized lesion stage. RESULTS: Complete response and objective response rates were 91% and 82% after TACE/RFA and 100% and 91% after RFA/TACE, respectively. Regarding Milan criteria, there was significant downstaging after RFA/TACE (P < 0.05). First and second overall survival rates were 85% and 65% after TACE/RFA versus 100% and 74%, respectively, after RFA/TACE (P > 0.05). Kaplan-Meier curve as regards disease-free survival rate, median time were 17.1 months [95% confidence interval (CI) 12.2-22.0] in TACE/RFA and 23.2 (95% CI 18.1-28.2) months in RFA/TACE (P > 0.05). CONCLUSION: RFA/TACE showed effective complete response, downstaging, disease-free survival and overall survival for the treatment of hepatic malignant tumors.

Annexin A2 as a biomarker for hepatocellular carcinoma in Egyptian patients.

AIM: To investigate the clinical utility of serum annexin A2 (ANXA2) as a diagnostic marker for early hepatocellular carcinoma (HCC). METHODS: This study was performed in HCC Clinic of Ain Shams University Hospitals, Cairo, Egypt and included: Group 1: Fifty patients with early stage HCC (Barcelona Clinic Liver Cancer stage A); Group 2: Twenty five patients with chronic liver disease; and Control Group: Fifteen healthy, age- and sex-matched subjects who were seronegative for viral hepatitis markers. The following laboratory investigations were done: Viral hepatitis markers [hepatitis B surface antigen and hepatitis C virus (HCV) antibodies], HCV RNA in HCV antibody-positive patients, serum alpha fetoprotein (AFP), and serum ANXA2 levels. RESULTS: In this study, 88% of HCC patients (n = 44) were HCV-positive, while HBV infection represented only 8% of all HCC patients (n = 4); and two patients were negative for both viral markers. A highly significant difference was found between patients with HCC and chronic liver disease as well as controls with regard to serum ANXA2 levels (130, IQR 15-240; 15, IQR 15-17; and 17, IQR 15-30 ng/mL, respectively). The area under the curve of ANXA2 was 0.865; the cut-off value was established to be 18 ng/mL with a diagnostic sensitivity of 74% and a specificity of 88%, while the sensitivity and specificity of AFP at the cut-off value of 200 ng/dL were 20% and 100%, respectively. CONCLUSION: Serum ANXA2 may serve as a biomarker for the early detection of HCC.

Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus.

BACKGROUND AND OBJECTIVES: Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). SUBJECTS AND RESULTS: 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×10(6) to 191×10(6). There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. CONCLUSION: SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis.

In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization?

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is one of the standard treatments recommended for intermediate stage hepatocellular carcinoma (HCC). At the same time, only little is known about the use of radioembolization with Yttrium-90 microspheres (TARE Y-90) for this subset of patients. To perform comparative analysis between both locoregional therapies in intermediate HCCs. Primary endpoint was overall survival (OS), while safety, response rate and time-to-progression (TTP) were considered as secondary endpoints. METHODS: We collected data of 86 HCC patients in two university hospitals at which conventional TACE with doxorubicin or TARE Y-90 using glass microspheres were performed. The median observation period was 10 months. Patients were followed up for signs of toxicity and response. They underwent imaging analysis at baseline and follow-up at regular time intervals. RESULTS: Eighty-six HCC patients with intermediate stage B (BCLC) were treated with either TACE (n = 42) or TARE Y-90 (n = 44). Despite a higher tumour burden in the TARE Y-90 group, the median OS (TACE: 18 months vs. TARE Y-90: 16.4 months) and the median TTP (TACE: 6.8 months vs. TARE Y-90: 13.3 months) were not statistically different. The number of treatment sessions, the average rate of treatment sessions per patient, total hospitalization time and rate of adverse events were significantly higher in the TACE cohort. CONCLUSION: In intermediate HCC stage patients, both treatments resulted in similar survival probabilities despite more advanced disease in the TARE Y-90 group. Still, TARE Y-90 was better tolerated and associated with less hospitalization and treatment sessions.

Risk factors for early intrahepatic distant recurrence after radiofrequency ablation for hepatocellular carcinoma in Egyptian patients.

OBJECTIVE: Early tumor recurrence, either local or intrahepatic distant recurrence (IDR), after successful radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remains a significant problem. The study aimed to determine the potential risk factors for IDR within one year after successful RFA in HCC patients. METHODS: In total, 105 patients with 138 lesions who underwent RFA and were followed up for at least one year were included in this study. The patients' data was retrospectively reviewed. Multiple host and tumoral potential risk factors were analyzed. RESULTS: IDR was found in 62 (59.0%) of all patients. Cumulative IDR-free survival rates in all patients studied were 81.9%, 45.4% and 35.2% at 1, 2 and 3 years, respectively, after RFA. Univariate and multivariate analysis showed that both tumor size >2.8 cm and primary multinodular tumors were significant risk factors for IDR within one year after RFA. CONCLUSIONS: Patients with tumors of >2.8 cm in diameter or multinodular HCC should be closely monitored for early recurrence after RFA. Combined or systemic therapies should be tried for these patients to improve their disease-free and overall survival.

Donor rejection before living donor liver transplantation: causes and cost effective analysis in an egyptian transplant center.

BACKGROUND: In the living donor liver transplant setting, the preoperative assessment of potential donors is important to ensure the donor safety. OBJECTIVES: The aim of this study was to identify causes and costs of living liver-donors rejection in the donation process. MATERIALS AND METHODS: From June 2010 to June 2012, all potential living liver donors for 66 liver transplant candidates were screened at the Ain Shams Center for Organ Transplantation. Potential donors were evaluated in 3 phases, and their data were reviewed to determine the causes and at which phase the donors were rejected. RESULTS: One hundred and ninety two potential living liver donors, including 157 (81.7%) males, were screened for 66 potential recipients. Of these, 126 (65.6%) were disqualified for the donation. The causes of rejection were classified as surgical (9.5 %) or medical (90.5 %). Five donors (3.9 %) were rejected due to multiple causes. Factor V Leiden mutation was detected in 29 (23 %) rejected donors (P = 0.001), 25 (19.8 %) donors had positive results for hepatitis serology (P = 0.005), and 16 (12.7 %) tested positive for drug abuse. Portal vein trifurcation (n = 9, 7.1%) and small size liver graft estimated by CT volumetric analysis (n = 6, 4.8 %) were the main surgical causes which precluded the donation. CONCLUSIONS: Among potential Egyptian living liver donors, Factor V Leiden mutation was a significant cause for live donor rejection. A stepwise approach to donor assessment was found to be cost-effective.

Epidemiological characteristics of hepatocellular carcinoma in Egypt: a retrospective analysis of 1313 cases.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. The aim was to study epidemiological characteristics of HCC in Egypt. METHODS: Retrospective chart review of 1456 Egyptian patients with HCC was done. Records of 1313 patients (1035 males, 278 females; median age 56 years) fulfilling diagnostic criteria for HCC were analysed for clinical, aetiological, radiological and tumour characteristics. RESULTS: The majority of cases (75%) were from rural areas. The most frequent age category affected by HCC was between 51 and 60 years (45.7%); 50% of the patients reported accidental discovery of their hepatic focal lesions. The major presenting symptom was newly developed right hypochondrial pain (66.3%). HCV Ab was detected in 91.32% of the studied patients while HVB infection was reported in 2.51%. 59.3% of patients had AFP levels below 200 ng/ml (the diagnostic level). On studying tumour characteristics, the right lobe of the liver was more frequently occupied by the focal lesions (75.4%) than the left lobe (15.7%) and 12.5% of patients had bilobar affection. Five hundred and six patients (38.6%) had more than one hepatic focal lesion and 228 patients (17.4%) had tumours occupying >50% of the liver. CONCLUSION: HCC is a major health problem in Egypt and its incidence is increasing. The high prevalence of HCV infection makes screening programmes and surveillance of those patients a very important tool to early detect cases of small HCCs.

Biliary complications including single-donor mortality: experience of 207 adult-to-adult living donor liver transplantations with right liver grafts.

BACKGROUND: After right lobe donation, biliary complication is the main cause of morbidity. Mortality after right lobe donation has been estimated to be less than 0.5%. PATIENTS AND METHODS: Between November 2001 and December 2008, 207 adult-to-adult living donor liver transplantations (ALDLT) were undertaken using right lobe grafts. Donors included 173 men and 34 women with a mean age of 28.4 +/- 5.2 years. RESULTS: Siblings comprised 144 (69.6%) cases whereas unrelated donors comprised 63 (30.4%) with a mean body mass index (BMI) of 25.2 +/- 2.4. Single and multiple right hepatic ducts (RHD) were present in 82 (39.6%) and 125 (60.3%) donors, respectively. Mean operative time was 360 +/- 50 min with an estimated blood loss of 950 +/- 450 ml and returned cell-saver amount of 450 +/- 334 ml. Mean donor remnant liver volume was 33.5 +/- 3.2%. Mean intensive care unit (ICU) stay was 3 +/- 0.7 days and mean hospital stay was 14 +/- 3.5 days. Modified Clavien classifications were used to stratify all donor biliary complications The overall biliary complications occurred in 27 cases (13.0%). After modified Clavien classification, biliary complications were graded as grade I (n= 10), grade II (n= 2), grade III (n= 14) and grade V (n= 1). Grade I and II (n= 12) biliary complications were successfully managed conservatively. Grade III cases were treated using ultrasound-guided aspiration (USGA), endoscopic retrograde cholangiography (ERCP) and surgery in 10, 2 and 2 donors, respectively. Single donor mortality (Grade V) (0.4%) occurred after uncontrolled biliary leakage with peritonitis that necessitated exploration followed by ERCP with stent insertion but the donor died on day 43 as a result of ongoing sepsis. CONCLUSION: Although the majority of biliary complications are minor and can be managed conservatively, uncontrolled biliary leakage is a serious morbidity that should be avoided as it could lead to mortality.

Recurrence-free survival after radiofrequency ablation of hepatocellular carcinoma. A registry report of the impact of risk factors on outcome.

BACKGROUND: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). METHODS: We studied 40 patients with 48 HCCs (< or = 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 +/- 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre- and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). RESULTS: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size > or = 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age > 65 years (P < 0.05). No significant risk factor relationship for IDR could be detected. CONCLUSION: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.