Does overt hepatic encephalopathy cause persistent cognitive defects even after successful liver transplantation?

Ever since the advent of liver transplantation, there has been great interest in how effectively this procedure reverses hepatic encephalopathy (HE). Most clinicians believe that the majority of the clinical features recognized as HE are reversed by successful liver transplantation.1 However, in this issue of Liver Transplantation, there is a report showing an incomplete reversal of certain cognitive defects in patients who had bouts of overt HE before they underwent liver transplantation.2 Interestingly, abnormal electroencephalographic patterns that were noted in all these patients completely normalized after transplantation, whereas previously abnormal domains of cognition improved over a 12-month period but still were not normal in patients with a pretransplant history of overt HE. There have been a number of studies suggesting that once patients have had a bout of overt HE, they may be at risk for a less-than-full recovery of brain function even after liver transplantation.3-5 Perhaps we might accept this lack of recovery in patients who have not received a new liver if they still appear to be normal on the surface. After all, HE therapy in patients with cirrhosis does appear to control overt HE, but a substantial number of patients treated with lactulose or rifaximin may still have minimal HE. Traditionally, in many contemporary studies of minimal HE, patients with previous overt HE have been excluded. It would be interesting to see whether the responses to HE therapy for minimal HE in patients with previous bouts of overt HE and patients without that history are different. Be that as it may, on the basis of the findings of the current study, we can conclude a few points. First, even though 23 of the patients (the total sample was 65) had histories of overt HE, it appears that none had overt HE around the time of transplantation. We assume that the patients were placed on therapy as is usual after bouts of overt HE. The domains of attention and executive function were more impaired in those patients who had previous bouts of overt HE even though they were treated for HE (we assume), and importantly, after liver transplantation, the performance on these domains remained lower than the performance of patients who had not experienced overt HE previously. In contrast, memory, which was also impaired before liver transplantation in patients who previously had overt HE, returned to a virtually normal state. Trail Making Test B seemed to be particularly sensitive for picking up the less reversible aspects of the domain of attention. This is well illustrated in Fig. 3 of the article. It must be admitted that the number of patients at the end of the study may have been insufficient to completely prove the lack of recovery in these patients. As mentioned earlier, if we accept that patients with a previous bout of overt HE may be unable to recover from a defect in the cognitive domain of attention or executive function even with a liver transplant, a more serious issue is raised. Should all patients undergo transplantation before their first bout of overt HE if this is possible?6 This radical suggestion is unlikely to be enacted, but an alternative idea may have traction. Looking at Figs. 3 and 4 of the article, we get the feeling that all of the psychometric test performances were steadily improving. Perhaps many patients just need more time to recover from a very demanding procedure and previous overt HE in order for their psychometric test performance to normalize. This interesting study may stimulate further research in this area.