*3.13. Local Experience*

The authors of this review run a daily, dedicated HE clinic within a tertiary referral hepatology centre [76]. While they adhere, as they have in this manuscript, to published treatment guidelines, it is their impression that routine clinical HE reality is complex, and its management more varied and in many ways more interesting and more satisfactory than one would expect. We utilise treatment to facilitate differential diagnosis, as patients with cirrhosis have multiple and often coexisting risk factors for neuropsychiatric impairment [77]: if HE is treated adequately one can rule out alternative diagnoses and/or establish their relative contribution to overall neuropsychiatric status. We use dietary changes, under strict and frequent monitoring, for highly recurrent and persistent HE, sometimes very successfully. We often resolve iatrogenic HE by simply easing strict dietary prescriptions (sometimes self-imposed) that have resulted in malnutrition and sarcopenia. We do not miss an opportunity to test experimental HE treatment strategies if co-morbidities allow us to do so safely. For example, we all recall a patient with shuntrelated, persistent HE whose neuropsychiatric status drastically improved when he was started on a brief course of a non-steroidal anti-inflammatory drug because of backache. We are fortunate enough to have the facilities [78] to test the effects of treatment over time in a comprehensive fashion, and to tailor treatment accordingly. We regret that this clinical experience, partly because of inherent difficulties in describing/summarising it and partly because of publication policies in relation to case reports/case series, remains largely unpublished and transferred to colleagues by traditional and somewhat haphazard teaching and collaboration strategies. Finally, we have sometimes been able to test treatment in controlled conditions, i.e., by inducing hyperammonaemia and then attempting to lower it in different ways [66]. We find this to be an under-utilised but potent tool to better understand the pathophysiology of HE [79], and thus, improve its management.

**Table 1.** Available treatments (other than general principles, non-absorbable disaccharides/antibiotics) with some commentary on the evidence for them and/or tips for use.


**Funding:** S.M. is grateful to the University of Padova (Supporting TAlent in ReSearch @University of Padova 2019).

**Conflicts of Interest:** S.M.'s group has received research funding from AlfaSigma S.p.a., Norgine Ltd., Merz Pharmaceuticals GmbH, Umecrine Cognition AB and Versantis AG.
