Splenectomy may improve the liver function, reverse hypersplenism and reduce portal pressure and thus decrease the occurrence of complications such as infection, ascites and variceal bleeding in cirrhotic patients
[9–13]. However, it may also compromise the immunity of the patients
[14, 15]. Therefore, best practice care is needed for asplenic patients
. For patients with HBV cirrhosis after splenectomy for hypersplenism and portal hypertension, the efficacy and safety of antiviral therapy have not been well documented although the benefit of antiviral therapy with nucleos(t)ide analogs has been demonstrated in most of the disease status of persistent HBV infection
[2–8]. In this study, we showed that the overall survival rate and complication-free survival rate in the treatment group was higher than those in the control group although the difference was not statistically significant. This may be the result of the insufficient numbers of patients in our cohort. The univariate analysis showed no significant factors which may predict the overall survival but the age of the patients was associated with complication-free survival. The multivariate analysis showed that the antiviral therapy, though not statistically significant, was associated with increased overall survival and significantly associated to increased complication-free survival of the patients. These results suggest that antiviral therapy also benefits this subgroup of patients and should be implemented in these patients after splenectomy. Of course, it is impartial to commence antiviral treatment before surgery for the HBV cirrhotics. Although antiviral therapy is becoming more and more common in HBV-associated disease, the awareness of antiviral treatment should still be emphasized because it is always not too late to initiate antiviral treatment at any stage of chronic HBV infection.
Serum AST level, international normalized ratio (INR) and HBeAg status were factors associated with overall survival in multivariate analysis. These parameters are reflections of the inflammation and synthetic function of the liver and the characteristics of the virus at splenectomy in the patients and thus may also affect the disease-associated survival after splenectomy. Another independent factor associated to the complication-free survival of the patients was the age of the patients at splenectomy. This is consistent with the long-term observation about the natural history of chronic HBV infection showing that older age at diagnosis is an important determinant of disease progression
[17, 18]. Notably, our results revealed that, even in the antiviral treatment group, the complication-free survival rate in younger patients was higher than that in older patients, suggesting that younger patients benefit more from the treatment.
There were no serious adverse effects associated with the use of nucleos(t)ide analogs in the present study. Understandably, the most significant concern associated with nucleos(t)ide analogs therapy is the emergence of resistant mutants
[19–21], which may lead to a relapse of hepatitis and result in fatal liver failure occasionally. In the present study, we did not determine the emergence of viral resistant mutants. Lamivudine in combination with adefovir dipivoxil was administered in 2 patients de novo to prevent the emergence of resistant mutants taking into account of their high HBV DNA levels and the lower rates of resistance and HBV DNA breakthrough as well as the higher rates of ALT normalization with de novo combination treatment in chronic hepatitis B patients
. None of the patients with nucleos(t)ide analogs developed breakthrough hepatitis in our cohort, probably thanks to the preventive de novo combination, the uninterrupted administration of the medicine in the patients and the good compliance in all the patients. With the advent of new and emerging antiviral agents such as tenofovir disoproxil and the optimization and combination of the therapeutics
[19, 21, 23], the emergence of resistant mutants will be well controlled.
One interesting and important issue is the effect of asplenic status on the seroconversion of HBeAg and/or HBsAg with antiviral therapy in the HBV patients. Unfortunately, we were not able to address this issue because of the actual difficulty to retrieve the virological data in most of our patients and to set a comparable group of HBV-related splenic cirrhotic patients. Theoretically, the asplenia status may reduce the seroconversion rate because of the absence of the role of spleen in both innate and adaptive immunity
[24–26]. Further studies are necessary to clarify the effect of splenectomy on the seroconversion with antiviral therapy in asplenic patients by comparative observation with splenic patients.
We believe that the antiviral treatment accounts for the improvement in cumulative complication-free survival rate and overall survival rate among patients in the nucleos(t)ide analogs group. However, our study is limited by the small sample size of patients studied, retrospective analysis in design, nonstandardized criteria to use the nucleos(t)ide analogs, lack of addressing the seroconversion and the short observation periods. The statistical power may be insufficient to detect a small susceptible effect of some factors. Therefore, prospective studies in larger sample size of patients with standardized criteria to use the nucleos(t)ide analogs and longer observation periods are needed to clarify the effects of nucleos(t)ide analogs on asplenic HBV cirrhotic patients. In fact, due to the rare condition and the lack of standardized criteria of antiviral therapy for asplenic HBV cirrhosis patients, prospective randomized trials with large numbers of patients seem infeasible, and we believe that our results derived from the retrospective data, do contribute to the understanding of commencement of antiviral therapy in this special subgroup of cirrhotic patients and add novel information for the management of HBV-associated diseases.
In summary, our present study showed for the first time to our knowledge that initiation of antiviral therapy with nucleos(t)ide analogs after splenectomy may reduce the occurrence of major complications and tend to improve the survival in asplenic HBV-associated cirrhotic patients. Multivariate analysis suggests that antiviral treatment and younger age were factors associated with reduced occurrence of complications in the asplenic HBV patients. Younger patients benefit more from the treatment after splenectomy. Our results therefore support the use of antiviral therapy in HBV cirrhotic patients even after splenectomy for hypersplenism and portal hypertension. Larger prospective studies are warranted to confirm our findings and to address the concerns whether antiviral therapy after splenectomy improves survival of the patients and affects seroconversion and viral resistance in the asplenic status.