In the current study, there was a significant reduction in the incidence of HE episodes in the simvastatin group (0/40), compared to the control group (15/40), and this is in accordance with the finding of studies which showed survival benefits and improvement in liver functions with simvastatin [14, 15]. Improvement in PHT, reduction in the incidence of HCC, and delays in hepatic decompensation have been associated with statin therapy among patients with cirrhosis [15, 16]. In our study, there was no significant difference between the two groups concerning INR, albumin level, total bilirubin, AST, and ALT, and this comes with an agreement with the findings in most of the studies discussing the impact of statins on the liver biochemical profile [17,18,19]. Statins are known to decrease Rho-kinase activity in activated hepatic stellate cells [11]. Besides, statins have anti-inflammatory, immunomodulatory, and antioxidant properties [12]. Simvastatin is also known to induce Krüppel-like factor 2, which improves liver fibrosis and PHT by increasing nitric oxide bioavailability [13, 14]. Generally, conflicting reports are available in the literature regarding liver function changes with statin use, with an insignificant risk of elevated transaminases [20, 21]. No significant difference was observed in the adverse effects noted during the study between the two groups in terms of diarrhea or worsening of ascites; however, there was a significant difference between the two study groups in myalgia, while other studies found no significant difference in adverse effect in the term of diarrhea, ascites, and myalgia noted during the study [17, 18]. Regarding the survival of patients in the two studied groups, there was a significant difference between them. This agrees with Motzkus-Feagans and his colleague [17] and agrees with a study done using the Veteran Affairs Clinical Case Registry [22]. This study described the effect of statins in cirrhotic HCV patients matched 1:5 with statin non-users, finding fewer decompensation episodes and death in statin users. No differences in comorbidities, metabolic conditions, or hepatic function were reported between the groups. The positive effect of statins in cirrhosis decompensation and mortality persisted at 10 years after adjustment for age, FIB-4 index score, serum level of albumin, model for end-stage liver disease (MELD), and CTP scores [22]. In our study, no significant difference was observed between the two groups as regards variceal rebleeding. This also agrees with the finding of Motzkus-Feagans et al., who proved that rebleeding rates were not different between the treatment and the control [17].
Regarding survival in CTP score A and B patients, there was a significant difference between the two studied groups. At the same time, there was an increased survival in group II patients compared to group I. The same finding was conveyed by Motzkus-Feagans and his colleague, who reported an increased survival in decompensated cirrhotic patients who received simvastatin after variceal bleeding [17]. Similarly, Pollo-Flores and colleagues reported the same findings after evaluating statin use in cirrhotic patients to look for increased mortality or decompensation with a mean follow-up of 36 months, including most cirrhotic patients at an early stage (CTP score A) [23]. They show that statin use was associated with lower mortality and fewer hepatic decompensation episodes in multivariate analysis.
More prolonged administration of simvastatin treatment than placebo for severe PHT was assessed in a blinded randomized controlled trial. Three months of 40 mg simvastatin in 24 patients, most CTP A and B nearly two-thirds with use of NSBB and medium/ large esophageal varices including 30% with previous variceal bleeding, showed a significant reduction in HVPG with greater effect in patients with previous variceal bleeding and medium/large esophageal varices. Again, no significant increase in adverse events from the use of simvastatin was reported [23]. Regarding survival in Child C patients, no significant difference was observed between the two studied groups, which matches the published data in this regard [17].
The current study has some limitations, such as the relatively small sample size, which could be attributed to our narrow inclusion criteria and the long-term follow-up required for the participants. Repeating the experiment with a larger sized sample could confirm our findings.