FYI...Review article: the design of clinical trials in hepatic encephalopathy - an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04590.x/abstract

Review article: the design of clinical trials in hepatic encephalopathy – an

International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN)

consensus statement

J. S. Bajaj1, J. Cordoba2, K. D. Mullen3, P. Amodio4, D. L. Shawcross5, R. F.

Butterworth6, M. Y. 7

Article first published online: 9 FEB 2011

DOI: 10.1111/j.1365-2036.2011.04590.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

Early View (Articles online in advance of print)

Summary

Background 

The clinical classification of hepatic encephalopathy is largely subjective,

which has led to difficulties in designing trials in this field.

Aims 

To review the current classification of hepatic encephalopathy and to develop

consensus guidelines on the design and conduct of future clinical trials.

Methods 

A round table was convened at the 14th International Society for Hepatic

Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points

were the nomenclature of hepatic encephalopathy and the selection of patients,

standards of care and end-points for assessing the treatment and secondary

prevention of hepatic encephalopathy.

Results 

It was generally agreed that severity assessment of hepatic encephalopathy in

patients with cirrhosis, whether made clinically or more objectively, should be

continuous rather than categorical, and a system for assessing the SONIC

(Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this

system, patients currently classified as having minimal hepatic encephalopathy

and Grade I hepatic encephalopathy would be classified as having Covert hepatic

encephalopathy, whereas those with apparent clinical abnormalities would

continue to be classified as overt hepatic encephalopathy. Some aspects of the

terminology require further debate. Consensus was also reached on the patient

populations, standards of care and endpoints to assess clinical trial outcomes.

However, some compromises had to be made as there is considerable inter- and

intravariability in the availability of some of the more objective surrogate

performance markers.

Conclusions 

The objectives of the round table were met. Robust, defendable guidelines for

the conduct of future studies into hepatic encephalopathy have been provided.

Outstanding issues are few and will continue to be discussed.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04590.x/abstract

Review article: the design of clinical trials in hepatic encephalopathy – an

International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN)

consensus statement

J. S. Bajaj1, J. Cordoba2, K. D. Mullen3, P. Amodio4, D. L. Shawcross5, R. F.

Butterworth6, M. Y. 7

Article first published online: 9 FEB 2011

DOI: 10.1111/j.1365-2036.2011.04590.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

Early View (Articles online in advance of print)

Summary

Background 

The clinical classification of hepatic encephalopathy is largely subjective,

which has led to difficulties in designing trials in this field.

Aims 

To review the current classification of hepatic encephalopathy and to develop

consensus guidelines on the design and conduct of future clinical trials.

Methods 

A round table was convened at the 14th International Society for Hepatic

Encephalopathy and Nitrogen Metabolism (ISHEN) meeting. Key discussion points

were the nomenclature of hepatic encephalopathy and the selection of patients,

standards of care and end-points for assessing the treatment and secondary

prevention of hepatic encephalopathy.

Results 

It was generally agreed that severity assessment of hepatic encephalopathy in

patients with cirrhosis, whether made clinically or more objectively, should be

continuous rather than categorical, and a system for assessing the SONIC

(Spectrum of Neuro-cognitive Impairment in Cirrhosis) was proposed. Within this

system, patients currently classified as having minimal hepatic encephalopathy

and Grade I hepatic encephalopathy would be classified as having Covert hepatic

encephalopathy, whereas those with apparent clinical abnormalities would

continue to be classified as overt hepatic encephalopathy. Some aspects of the

terminology require further debate. Consensus was also reached on the patient

populations, standards of care and endpoints to assess clinical trial outcomes.

However, some compromises had to be made as there is considerable inter- and

intravariability in the availability of some of the more objective surrogate

performance markers.

Conclusions 

The objectives of the round table were met. Robust, defendable guidelines for

the conduct of future studies into hepatic encephalopathy have been provided.

Outstanding issues are few and will continue to be discussed.