Hepatoencephalopathy

RE: Hepatoencephalopathy

Clive Ansell — Fri, 06 Sep 2019 12:38:10 GMT

[quote user="Andrew Kent"]I would agree at that level that portosystemic shunting is likely - although could always be something else as well causing the seizures![/quote]

Andy - thanks again for help.

we are confined by costs and owner compliance with this case, but have started medical management and will reassess in a month

There may be other differentials I know, but unlikely to be able to investigate in this case.

[quote user="Andrew Kent"]Do let us know whether the signs improve on HE treatment.[/quote]

Shall do

RE: Hepatoencephalopathy

Andrew Kent — Thu, 05 Sep 2019 20:47:44 GMT

[quote user="Clive Ansell"]post prandial 117[/quote]

I would agree at that level that portosystemic shunting is likely - although could always be something else as well causing the seizures!

Do let us know whether the signs improve on HE treatment.

Andy

RE: Hepatoencephalopathy

Christopher Scudder — Thu, 05 Sep 2019 13:24:39 GMT

Hi,

I did some research for hepatic encephalopathy for the PROTECT poster and this is what I found:

Hepatic Encephalopathy

Although the complete pathophysiology of hepatic encephalopathy remains uncertain, ammonia is believed to be key component of this condition. Roughly 50% of intestinal ammonia is formed in the small intestines as a by-product of bacterial glutamine degradation and 50% in the colon as a by-product of bacterial metabolism of protein and urea . Additional bacteria-derived toxins might also contribute to HE pathogenesis: mercaptans formed from bacterial metabolism of methionine and short chain fatty acids such as butyrate, valerate and phenols.

Most therapies are aims at reducing intestinal ammonia production and increasing faecal ammonia elimination. Lactulose and low protein diet remain the mainstay of the management of hepatic encephalopathy. Lactulose reduces glutamine uptake by small intestinal enterocytes. Ammonia absorption in colon occurs via urea absorption, glutamine absorption and nitrogen breakdown. Ureolysis and colonic nitrogen breakdown are the two major routes. Lactulose appears to alter colonic luminal pH and bacterial metabolism which results in a reduction of colonic ammonia production by increased bacterial mass and decreased colonic nitrogen absorption by conversion of ammonia into ammonium. Soluble fibre of vegetable origin also increases colonic nitrogen incorporation into bacteria. Lactulose has shown to be unequivocally beneficially in the management of HE in humans but has not been shown to affect mortality rates. In addition, a recent Conchane review concluded lactulose was inferior to antibiotics in reducing blood ammonia and HE symptoms.

The rationale for antibiotic usage was reduction of urease producing bacteria. According to American College of Gastroenterology. Antbiotics should be reserved for patients who do not respond to diet and lactulose therapy (Blei & Córdoba 2001). An antibiotic which disrupts the intestinal microbiota diversity as little as possible while having beneficial clinical effects is favourable.

Neomycin is poorly absorbed by the gastrointestinal tract and show to reduce gastrointestinal urease activity and also been shown to be effective I the management of HE in people. However, sufficient quantities can be absorbed to risk ototoxicity.

Metronidazole has been considered second line in human medicine despite a lack of proven efficacy. This antibiotic is also associated with risk of neurological toxicity which remains a concern with it’s use. Metronidazole use in dogs is associated with a reduction of bacterial biodiversity which could result in detrimental effects, however it’s use is associated with increased Bifidobacterium numbers (Igarashi et al. 2014). As these bacteria are able to lower intestinal pH by lactose fermentation, use of this antibiotic could be a beneficial by reducing intestinal ammonia absorption (Jiang & Savaiano 1997).

Rifaximin is an antibiotic with is becoming increasingly recognised as an effective treatment for HE in humans (Bucci & Palmieri 1993; Bass et al. 2010). It is a semisynthetic, gut-selective, and nonabsorbable oral antibiotic which locally in the gastrointestinal tract. It is active against a variety of aerobic and anaerobic Gram-positive and Gram-negative organisms, as well as protozoal infections. It has been used in dogs and shown to be an alternative to metronidazole in the treatment of antibiotic responsive diarrhoea (Menozzi et al. 2016). However, it’s current cost limits it’s use for most patients.

Amoxicillin or ampicillin are commonly recommended antibiotics for the treatment of HE in dogs. However, use is associated with induction of multiple antibiotic-resistant bacterial populations and development of dysbiosis (Grønvold et al. 2010). Use of these antibiotics are also likely to result in greater gastrointestinal gram negative bacterial load, which might be a contributor to gastrointestinal inflammation (Honneffer et al. 2014; Omori et al. 2017).

Tetracyclines, chloramphenicol, lincomycin, sulphonamides and erythromycin should be avoided due to the potential for hepatotoxicity ans requirement for hepatic metabolism.

Concluding remarks:

Diet and lactulose should be first line therapies in the management of patients with HE. The lack of evidence of use of antibiotics in either veterinary or human medicine is surprising and an area for SAMSoc to investigate further. If we were to recommend an antibiotic as a second line therapy, then I think metronidazole would be my preferred on the weight of it.

Bass, N.M. et al., 2010. Rifaximin Treatment in Hepatic Encephalopathy. New England Journal of Medicine, 362(12), pp.1071–1081.

Blei, A.T. & Córdoba, J., 2001. Hepatic Encephalopathy. The American journal of gastroenterology, 96(7), pp.1968–1976.

Bucci, L. & Palmieri, G.C., 1993. Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Current medical research and opinion, 13(2), pp.109–18.

Grønvold, A.M.R. et al., 2010. Changes in fecal microbiota of healthy dogs administered amoxicillin. FEMS Microbiology Ecology, 71(2), pp.313–326.

Honneffer, J.B., Minamoto, Y. & Suchodolski, J.S., 2014. Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs. World Journal of Gastroenterology, 20(44), pp.16489–16497.

Igarashi, H. et al., 2014. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs. PLoS ONE, 9(9).

Jiang, T. & Savaiano, D.A., 1997. Modification of colonic fermentation by bifidobacteria and pH In Vitro: Impact on lactose metabolism, short-chain fatty acid, and lactate production. Digestive Diseases and Sciences, 42(11), pp.2370–2377.

Menozzi, A. et al., 2016. Rifaximin is an effective alternative to metronidazole for the treatment of chronic enteropathy in dogs: A randomised trial. BMC Veterinary Research, 12(1), pp.1–9.

Omori, M. et al., 2017. Fecal microbiome in dogs with inflammatory bowel disease and intestinal lymphoma. Journal of Veterinary Medical Science, 79(11), pp.1840–1847.

RE: Hepatoencephalopathy

Clive Ansell — Thu, 05 Sep 2019 10:10:14 GMT

[quote user="Andrew Kent"]How high were the bile acids out of interest?[/quote]

Hi Andy, thanks for your post.

pre prandial BA 15 (ref range 0-9)

post prandial 117

All other bloods including toxoplasma serology, and all hepatic enzymes all wnl

RE: Hepatoencephalopathy

Clive Ansell — Thu, 05 Sep 2019 10:07:37 GMT

[quote user="Sara Ramsey"]Also, inflammation some where could be involved in a worsening of symptoms if it does have a PSS - does it have any other disease processes?[/quote]

Not that we are aware of, other than being overweight . Other than raised bile acids, all of remaining bloods were normal.

RE: Hepatoencephalopathy

Andrew Kent — Wed, 04 Sep 2019 12:39:17 GMT

Hi Clive,

Agree with others that in most PSS patients that seizure we will see a good improvement on medical therapy for HE. In this breed the situation can be more complex due to concurrent brain disease.

How high were the bile acids out of interest?

My initial combo for HE would be dietary manipulation (I now use soya based diets such as Purina HA as non-meat diets are less ammoniogenic and, as other have said, we often don't need the excessive protein restriction of a hepatic diet), lactulose + antibiotics (I use metronidazole at 7-8mg/kg BID). Longer-term (if not having surgery) many patients can be de-escalated to only diet + lactulose or even only diet sometimes.

Levetiracetam would be a good choice if additional seizure control is needed.

Andy

RE: Hepatoencephalopathy

Iain Richards — Wed, 04 Sep 2019 11:22:15 GMT

[quote user="Richard Carter"]

reduce ammonia production in git , help with compromised hepatic retic endothelial immune system with digested food going straight into circulation without being filtered

[/quote] Thanks. Something else added to the grey cells.

RE: Hepatoencephalopathy

George Cooper — Wed, 04 Sep 2019 10:46:17 GMT

I’d a yorkie that I rescued that had initially crystalluria and was investigated and found to have hepatic encephalopathy.

We managed her with oral amoxyllin, lactulose, and a diet of cottage cheese and pasta. Lived to a good age.

RE: Hepatoencephalopathy

Richard Carter — Wed, 04 Sep 2019 10:10:52 GMT

reduce ammonia production in git , help with compromised hepatic retic endothelial immune system with digested food going straight into circulation without being filtered

RE: Hepatoencephalopathy

Iain Richards — Wed, 04 Sep 2019 08:49:20 GMT

What's the rationale for the antibiotics please? Memory getting a little dusty

RE: Hepatoencephalopathy

Sara Ramsey — Tue, 03 Sep 2019 22:50:46 GMT

Also, inflammation some where could be involved in a worsening of symptoms if it does have a PSS - does it have any other disease processes?

RE: Hepatoencephalopathy

Sara Ramsey — Tue, 03 Sep 2019 22:48:21 GMT

With respect to diet, Penny Watson advises that they are usually too low in protein when the animal is already in a catabolic state. Using a highly digestible diet, fed several times a day is what I was recommend.

RE: Hepatoencephalopathy

Julie Innes — Tue, 03 Sep 2019 16:04:03 GMT

Another for lactulose and metronidazole, although I'm old enough to remember a neomycin(?)/ kaloin mix that was once used in these guys (Kaobiotic)! I remember one owner feeding one on roast potatoes at one time!

RE: Hepatoencephalopathy

Emily Rainbow — Tue, 03 Sep 2019 15:20:16 GMT

Could also use keppra for 3-5d after next seizure to see if extends seizure frequency?

RE: Hepatoencephalopathy

Richard Carter — Tue, 03 Sep 2019 13:59:03 GMT

our pss cases are managed with low dose metronidazole (10mg/kg) and lactulose and careful feeding - usually cottage cheese diet. we never use the metrobactin data sheet dose levels - far too high.

others were better on amoxycillin (without clav) and lactulose