Christian, in my current project we have seen that lactulose is a good option to treat HE, without side effects. Weight gain and eating behavior are normal in rats with HE treated with lactulose when compared to control group, without treatment. Moreover, they have a significantly decrease in the ammonia levels and show a improve of behavior, in the same way it is observed in humans. We are still analysing other parameters. Despite, I agree with you about the efficacy of Rifaximin, that has been show in many researches, but i don't know about the especific effects of this treatment especially related to behavior that could improve the quality of life, how you asked. I recently saw a review about HE and the author showed that both (lactulose and rifaximin), when used together, has better effects than used alone. I think it needs to be investigated with more details in rats and, if possible, in humans, with different amount, period and frequency.

Hello Christian. Its good to see clinicians considering the significance of nutrition and QOL in HE. I would tend to agree with Natalia's observation about combining Lactulose with rafaximin and there are a number of authors who support this approach. There is currently a publication entilted Hepatic Encephalopathy: an Update, Clinics in Liver Disease; Ed Mullen & Prakash, Feb 2012 Vol 16, No 1, published Saunders, which has an excellent chapter "Malnutrition in Cirrhosis: Contribution and Consequences of Sarcopenia on Metabolic and Clinical Responses" by Periyalwar and Dasarathy, which is well worth a look. There is also a chapter entitled " Hepatic Encephalopathy and Health-Related Quality of Life" by Bianchi, Giovagnoli, Sasdelli & Marchesini. Overall, its an excellent publication.

Perhaps, it would be a good deal far from the point of the question, but I recollect a famous fact that the octopus, rather an intelligent creature, can live without liver at all. May it be worth to abandon the Lactulose for a while (just stop to invent the uninventable) and take a look at the unvertabrates physiology? :))

A nice review article from the Montreal group in Journal of Nutrition and MetabolismVolume 2010 (2010), "Role of Nutrition in the Management of Hepatic Encephalopathy in End-Stage Liver Failure" Full text at:

http://www.hindawi.com/journals/jnume/2010/489823/

The greatest impairment with HE is cognitive and behavioral with resulting impact on capability to perform Activities of Daily Living (ADL). The potential for nutritional interventions is (1) to correct the deleterious effects of basic undernutrition ("malnutrition") common to most patients with chronic liver disease, cirrhosis, and HE, and (2) to make specific targeted interventions to mitigate the effects of patient with HE pathophysiology related to impairments in capacity to process nutrients like proteins and amino acids. Basic nutritional intervention strategies can be applied when underlying nutritional deficiencies are identified (vitamin B12, folate, minerals, etc). Targeted nutritional interventions (reduced or increased intake of specific amino acids, protein types, fatty acids, etc) can be useful in patients with refractory HE that do not respond to usual management such as lactulose, general protein restriction, etc. In such case, supplementing branched-chain amino acids and reducing aromatic amino acids have proven beneficial. Until human evolves into the octopus, we must continue to strive to improve quality of life for those with end stage liver disease who are waiting (or excluded) from liver transplant.

Thank you for the link for gorgeous an article!

A question: is there any novel data as to substances that induce HE? As far as I remember, there has been no convincing evidence untill now in the world literature that a certain substance is a main cause of the hepatic encephalopathy.

As for the octopus, I might be excused by the fact that these smart creatures have not the liver only, but hemoglobin and the products of its degradation accordingly. It has got inspite hemocyanin the breath pigment with Cu inspite of Fe. It is not toxic, so it is soluted directly in blood, tinting it blue.

On the other hand, during the evolution process the liver, hemoglobin (rather a toxic matter with properties of the strong acid) and erythrocytes, its specific cell-transporters seems to develop simultaneously in the same time with the vertebrates appearance. The fact that proved by the human erythropoesis starts in the liver bud at first. The amphioxus, the primitive chordate, which anatomy the students learn at classes in school and university, has no hemoglobin, erythrocytes and liver itself.

When I was young, a non-hemoglobin solution for the shock and liver failure resuscitation was invented. Its name was perphthoran, or simply 'the blue blood'.

Lactulose diet and expensive wide-spectrum antibiotic (Rifaximin) therapy in the liver cirrhosis patients:

Both are not more than methods of palliative therapy. By definition, they are able just to give timely and tiny advantages, if any.

In spite of highly pretentious name, so called the evidence-based medicine remains a tool that is rather rood and primitive one yet. To prescribe a lactulose diet or\and wide-spectrum antibiotics is a wage and too general recommendation. Let us to consider what could be their mechanisms of action, when and how they could work? What kind of results a physician should wait for from the kind of therapy?

The goal of the lactulose ingestion instead of the glucose is to diminish the activity and, virtually, amount of the glucose-fermented intestinal microflora that is, in its turn, the putative main source of the hepatic encephalopathy. The theoretical basis of this therapy were: 1) the experimental studies on the rodents with toxin-induced liver cirrhosis, and 2) cohort studies on the LC patients (approximately a half of which became better for some time after the therapy). This therapy is not individualized!

Questions that one could raise as to those studies (and as the basis, accordingly):

1) What studies were performed as to the intestinal microflora quality and quantity changes in humans after longtime lactulose diet? Was their rest food standartisized?

2) What studies were performed as to the small intestine bacterial overgrowth presence in the liver cirrhosis patients at all, and after the lactulose diet in part? And after the appropriate Rifamixin treatment?

3) Why should we believe in that any liver cirrhosis patient has that very kind of the intestinal microflora-dependent encephalopathy that caused by namely the glucose-fermented bacteria?

4) ‘The HE patient eventually needs a Liver transplant but the health state in which he reaches that destination is in our hands’. What is in our hands really and to what extent?

In short,

If you have $1.000.000 per case, what diagnostics ans treatment would you prescribe for the HE patient that needs liver transplantation?

One issue that has not been mentioned so far in relation to nutrition and QOL in patients with HE is the effect of family/social circle on having/maintaining adequate nutritional intake. Does the patient have access to family members or friends or council services ie meals-on-wheels (provided in australia by council services) that provide/cook, encourage and support a good nutritional intake. Without family/social supports, I have found many patients with Cirrhosis and a history of HE perform very poorly in QOL and the ability to sustain adequate nutritional intake. Think of ETOH abuse/IVDU and the often isolated, dysfunctional life many of these patients with HE have. Often patients are discharged from hospital after a bout of HE and then present to hospital again with HE, begging the question, "what actually took place during that time?" I once cared for a lady who was Child-Pugh C throughout the last 5 years of her life with intermittent admissions due to HE. I believe she would have presented much more frequently if not for the care and devotion of her two daughters, who, living close by, were able to monitor her health and any signs of impending HE, while providing/encouraging her with her nutritional intake and assisting her to do some of the activities in life that she enjoyed most.