Risk Of Hepatitis B Virus Reactivation Of HCC Patients Underwent Microwave Ablation

Part one HBV reactivation after microwave ablation or hepatic resection for HBV-related hepatocellular carcinomaBackgroundHepatitis B virus infection is a global public health problem. China has about 93 million patients with HBV infection and 20 million chronic HBV carriers. Although HBV is a kind of non-cytotoxic virus, the host immune response caused by HBV replication can lead liver damage, cirrhosis, and even liver cancer. Although there are lots of treatment options available (including surgical resection, ablation, chemoembolization, radiotherapy et al), the prognosis of HBV-related HCC patients is still poor. One of the most important reasons is that HBV reactivation after treatments can result in a further deterioration of liver function and high recurrence rate. Microwave ablation as a safe and effective minimally invasive treatment technology has been widely applied in liver cancer in china. But we still don’t know whether HBV-related HCC patients will reactivate HBV replication after MWA. This study focuses on the incidence of HBV reactivation after MWA and hepatic resection and the relationship between HBV reaction and postoperative liver function recovery.MethodFrom Mar 2013 to May 2014, a retrospective study was conducted on 436 HBV-related HCC patients who were diagnosed as having initial HCC and underwent MWA or hepatic resection in the Department 1 of Minimally Invasive Therapy aof the Eastern Hepatobiliary Surgery Hospital. The inclusion criteria for this study were as follows:1. Initial early stage HCC (solitary tumor≤5 cm in diameter, or≤3 nodules and each≤3cm in diameter); 2. Patients who did not receive any antivirus therapy.3. HBsAg positivity for more than 6 months and HBV DNA load≤9999 IU/mL; 4. Adequate baseline liver function (Child-Pugh grade A or B); 5. Adequate renal function (serum creatinine<124 umol/L); Exclusion criteria were:1. HBsAg negativity or HBsAg positivity for less than 6 months or HBV DNA load≥10,000 IU/mL; 2. Taking any other antivirus medications except ETV; 3. Co-infection with other hepatotropic viruses or human immunodeficiency virus (HIV); 4. Any previous treatment for HCC and loss to follow-up within 4 months after MWA; 5. Poor liver function such as child-Pugh grade C,platelet count(PLT)<40×109/L and so on;6. Obstructive jaundice or co-existing severe non-malignant illness or any concurrent malignancy. Totally 56 patients met the study inclusion criteria. Among the 30 patients from MWA group,24 patients are male and 6 are female. And their mean age is 54.4±11.2 years. There are 26 patients in hepatic resection group.18 of them are male and 8 are female, mean age is 55.6±9.7 years. To investigate the incidence of HBV reactivation after MWA and the relationship between postoperative liver function recovery and HBV reactivation. The results were expressed as mean± standard deviation or median. Continuous variables were compared using the independent sample t-test and categorical variables were compared using the X2-test or Fisher’s exact test when appropriate. Differences with a P value less than 0.05 were considered statistically significant. Statistical analysis was performed using the SPSS version 21.0 software.ResultTotally,10 patients developed HBV reactivation,2 in the MWA group and 8 in the hepatic resection group. The incidence of MWA induced HBV reactivation is 6.7% and the incidence of hepatic resection is 30.1%(P<0.05). On univariate analysis, high HBV DNA load and hepatic resection were found to be significantly correlated with the occurrence of HBV reactivation. Patients were divided into two groups by whether developed HBV reactivation or not after MWA. Significant differences were observed in ALT levels between two groups at the second week and the fourth week after MWA or hepatic resection. No serious complications (including obstructive jaundice, bleeding, death etc) were observed in the MWA group. But there is one patient developed liver abscess in the MWA group. There are two patients developed subphrenic abscess and one patient became bile leakage.ConclusionIn summary, we could get the following conclusions:1. MWA is a safe and effective minimally invasive technique.2. MWA has lower risk of developing HBV reactivation than hepatic resection.3. Receiving ETV antivirus therapy after developing HBV reactivation, can effectively control HBV replication and prevent liver damage.Section two:Risk of Hepatitis B virus reactivation of HCC patients underwent Microwave ablation following prophylactic antiviral therapyBackgroundHCC has become the fifth biggest cancer among male in the world. There are approximately 554 thousand new HCC patients per year. In China, HCC is one of the most common malignant tumors and ranks the second cancer killer. The main risk factors of HCC include HBV, HCV, diabetes, obesity, alcoholism and metabolic diseases. These are also associated with fibrosis and cirrhosis of liver. As everyone knows, most HCC patients come from chronic liver disease (especially HBV-induced cirrhosis) in china. Nowadays, china has a large number of HBV infected patients (about 93 million). Among them,20 million are chronic HBV carriers. Since 1975 Wands discovered HBV reactivation phenomenon, doctors have come to realize that HBV reactivation is common in clinical work and can affect the liver function and even can cause tumor recurrence. HBV reactivation has been reported in many areas, but it’s not clear in the field of MWA. MWA as a safe effective and low complications minimally invasive technique has been widely used in china. This research mainly discusses HBV reactivation rate after MWA, mechanism of HBV reactivation, relationship between HBV reactivation and the recovery of liver function, relationship between HBV reactivation and HCC recurrence.MethodFrom May 2013 to July 2014, a prospective study was conducted on 821 consecutive patients with chronic HBV who were diagnosed as having initial HCC and underwent MWA in the Department 1 of Minimally Invasive Therapy of the Eastern Hepatobiliary Surgery Hospital. The inclusion criteria for this study were as follows:1. Initial early stage HCC (solitary tumor≤5 cm in diameter, or≤3 nodules and each≤3cm in diameter); 2. Receiving ETV therapy (Baraclude, SinoAmerican Squibb Pharmaceuticals) for more than 1 year or with no antivirus therapy, HBsAg positivity for more than 6 months, and HBV DNA load≤9999 IU/mL; 3. Adequate baseline liver function (Child-Pugh grade A or B); 4. Adequate renal function (serum creatinine≤124 umol/L). Exclusion criteria were:1. HBsAg negativity or HBsAg positivity for less than 6 months or HBV DNA load≥10,000 IU/mL; 2. Taking any other antivirus medications except ETV; 3. Co-infection with other hepatotropic viruses or human immunodeficiency virus (HIV); 4. Any previous treatment for HCC and loss to follow-up within 4 months after MWA; 5. Poor liver function such as child-Pugh grade C,platelet count(PLT)<40×109/L and so on; 6. Obstructive jaundice or co-existing severe non-malignant illness or any concurrent malignancy.Among 821 patients, totally 123 patients met the criteria of the study and were followed up 4 months after MWA. There were 60 patients without any antivirus threapy in the non-antivirus group and 63 patients with ETV therapy belonged to the ETV group. We want to investigate the risk factors of HBV reactivation after MWA; the influence of HBV reactivation on the recovery of liver function; the relationship between HBV reactivation and HCC recurrence. The results were expressed as mean±standard deviation or median. Continuous variables were compared using the independent sample t-test and categorical variables were compared using the X2-test or Fisher’s exact test when appropriate. Univariate analysis followed by multivariate analysis using logistic regression was undertaken to identify risk factors of HBV reactivation. Differences with a P value less than 0.05 were considered statistically significant. Statistical analysis was performed using the SPSS version 21.0 software.ResultA total of 12 patients developed HBV reactivation. The incidence of MWA induced HBV reactivation is 9.7%. The incidence of HBV reactivation in the control group and ETV group was 16.7% and 3.2% respectively. On univariate analysis, No. of tumor (P=0.042), detectable HBV DNA load (P=0.009), and without antiviral therapy (P=0.012) were found to be significantly correlated with the occurrence of HBV reactivation. While on multivariate analysis of these 17 variables using a logistic regression, only detectable HBV DNA load (OR,5.594; 95% CI 1.356-23.076, P=0.017) and without antiviral therapy (OR,9.324; 95% CI,1.713-50.745, P=0.01) remained to be significantly associated with HBV reactivation. ALT level between patients with HBV reactivation and without HBV reactivation showed significantly different at week 2 and 4, then appeared to be no significantly different at week 8,16. Totally 7 patients developed HCC recurrence in the control group and 4 in ETV group. HCC recurrence rate in patients with HBV reactivation and without HBV reactivation was 33.3%(4/12) and 6.3%(7/111) respectively.ConclusionOur result demonstrated that1. MWA could reactivate HB V replication during the perioperative period, especially in those patients who didn’t receive any antiviral therapy.2. HBV reactivation can lead liver function deterioration and increase HCC recurrence rate.3. HBV must be monitored after MWA and antivirus therapy can prevent HBV reactivation, control liver damage, and reduce the recurrence rate of HCC.