Keywords: Autoimmune hepatitis, Liver failure, Liver transplantation, development of hepatic encephalopathy and coagulopathy within 8 wk. Prognosis of acute severe autoimmune hepatitis (AS-AIH): the role of (1) Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS Glucocorticoids/adverse effects; Hepatic Encephalopathy*/etiology. Hepatic encephalopathy (HE) occurs when the liver stops working properly non-alcoholic fatty liver disease, alcohol, autoimmune hepatitis.
Autoimmune Hepatic Hepatitis Encephalopathy,
If encephalopathy develops in acute liver failure type A , even in a mild form grade 1—2 , it indicates that a liver transplant may be required, and transfer to a specialist centre is advised. In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management.
In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. This has been shown to be incorrect. Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight.
A diet with adequate protein and energy is therefore recommended. Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis. Lactulose lactitol are disaccharides that are not absorbed from the digestive tract. This may relieve constipation, one of the causes of encephalopathy, and increase bowel transit. Lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment.
The possible side effect of bloating may interfere with a liver transplant procedure if required. The antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease.
This is thought to work in a similar way to other antibiotics, but without the complications attached to neomycin or metronidazole. Due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. When rifaximin is added to lactulose, the combination of the two may be more effective than each component separately. The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy.
Neomycin was chosen because of its low intestinal absorption , as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. Later studies showed that neomycin was indeed absorbed when taken by mouth , with resultant complications. Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage , in addition to gastrointestinal side effects.
Together with the severity of encephalopathy, these markers have been incorporated into the Child-Pugh score ; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation. In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality, and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis.
Historically, widely used criteria for offering liver transplantation, such as King's College Criteria , are of limited use and recent guidelines discourage excessive reliance on these criteria. The occurrence of hepatic encephalopathy in people with Wilson's disease hereditary copper accumulation and mushroom poisoning indicates an urgent need for a liver transplant.
The occurrence of disturbed behaviour in people with jaundice may have been described in antiquity by Hippocrates of Cos ca. Many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, Giovanni Battista Morgagni — reported in that it was a progressive condition.
In the s, several reports enumerated the numerous abnormalities reported previously, and confirmed the previously enunciated theory that metabolic impairment and portosystemic shunting are the underlying mechanism behind hepatic encephalopathy, and that the nitrogen-rich compounds originate from the intestine.
The same group investigated protein restriction  and neomycin. The West Haven classification was formulated by Prof Harold Conn — and colleagues at Yale University while investigating the therapeutic efficacy of lactulose. From Wikipedia, the free encyclopedia. Hepatic encephalopathy Synonyms Portosystemic encephalopathy, hepatic coma,  coma hepaticum Micrograph of Alzheimer type II astrocytes , as may be seen in hepatic encephalopathy. The New England Journal of Medicine.
Archived from the original on 5 July Retrieved 30 July Ferri's Clinical Advisor E-Book: Archived from the original on Harrison's Principles of Internal Medicine 16th ed. Cochrane Database Syst Rev 4: J Clin Exp Neuropsychol. The Cochrane Database of Systematic Reviews. A double blind controlled trial". Encephalitis Viral encephalitis Herpesviral encephalitis Limbic encephalitis Encephalitis lethargica Cavernous sinus thrombosis Brain abscess Amoebic.
Autoimmune hepatitis AIH is a disease that is characterized by chronic hepatic inflammation, presence of autoantibodies [antinuclear antibody ANA , anti-smooth muscle antibody SMA , and liver kidney microsomal LKM antibody], female preponderance and elevated serum gammaglobulins, especially IgG[ 1 ]. AIH can have protean manifestations, with the majority of patients presenting with subclinical or chronic disease.
Fulminant hepatic failure FHF is a devastating clinical condition that occurs in patients with no prior history of liver disease, and is characterized by development of hepatic encephalopathy and coagulopathy within 8 wk after onset of jaundice[ 9 ]. In contrast, those with subacute LF present with encephalopathy at wk after onset of symptoms[ 10 ]. Unfortunately, neither the International Autoimmune Hepatitis Group IAIHG criteria[ 14 ] nor the simplified diagnostic criteria for diagnosis of AIH[ 15 ] have been extensively validated in patients with LF; largely because of the small number of cases encountered.
Thus, diagnosis of AIH and LF remains clinical and is supported by positive autoantibodies, negative viral serology, absence of alcohol excess and culprit drugs, and compatible liver biopsy. Although challenging, AIH can still be diagnosed in such a scenario by excluding other liver diseases, and by testing for other autoantibodies [perinuclear antineutrophil cytoplasmic antibodies pANCA , and antibodies to soluble liver antigen SLA ][ 18 , 19 ]. Nonetheless, the decision to initiate corticosteroids in patients who do not fulfill conventional diagnostic criteria for AIH must be made on an individual basis, and remains the prerogative of the treating hepatologist.
There is a paucity of published data on patients with AIH with LF at initial diagnosis; consisting mostly of anecdotal case reports or small case series[ 20 , 21 ]. Much of the controversy hinges on a critical management issue, namely should such patients be given a trial of corticosteroids, be priority listed for LT, or both.
If corticosteroids are indeed initiated, how and at what time point do we define failure of medical treatment? This editorial attempts to address some of these controversies with the aim to develop strategies that could optimize management of patients with AIH that present with LF.
Only studies providing data on type and duration of immunosuppressive therapy and outcomes were included. It is well known that these factors have a prognostic value in patients with AIH and in those with LF[ 7 , 26 - 28 ]. In addition, all the studies were retrospective, and one has only been published in an abstract form[ 22 ]. Nonetheless, these five studies do provide valuable information about the natural history of AIH with LF at initial presentation.
Clinical characteristics of patients with autoimmune hepatitis with liver failure at initial presentation.
In these five studies, the prevalence of LF at initial presentation in patients with AIH varied from 8. In all but one patient this was the first presentation of their disease. Of the total of 85 patients, 69 For the majority of the patients, there was no rationale provided for initiation or withholding corticosteroids, and the decision appeared to have been made on an ad hoc basis.
The remission rates with immunosuppression varied from 8. Outcomes of patients with autoimmune hepatitis and initial presentation with liver failure. The variability in remission rates with corticosteroid therapy in these five studies is most certainly a reflection of the heterogeneous patient population. Unsurprisingly, the lowest remission rates were seen in the study of Ichai et al[ 25 ], which had the sickest patients, as reflected by their high admission MELD scores.
The duration of steroid therapy prior to death was highly variable d. Nevertheless, in these five studies, there were a subset of patients with AIH and LF in whom death may have been preventable had LT been more aggressively pursued. It is conceivable that initiation of steroids provided a false sense of security, thereby delaying transplant evaluation. One could argue that the low remission rates to corticosteroids in this cohort were partly related to delay in initiating therapy.
However, where available, the data do not support this conclusion, as corticosteroids were initiated promptly, especially in the sicker patients. In our study, subsequent non-responders to corticosteroids were commenced on therapy within 2. It is more likely that non-responders to corticosteroids had aggressive disease at the time of diagnosis with a critical degree of liver cell death already having occurred prior to the introduction of medical treatment[ 24 ].
Assessing patients with LF for LT is a complex process. As is evident from the published data[ 7 , 22 - 25 ], there certainly are a subset of patients with AIH and LF who will respond to corticosteroids. Inappropriate transplantation in such patients would mean subjecting them to unnecessary surgery and its attendant complications and lifelong immunosuppression.
In addition, it would deprive another more suitable recipient from receiving the graft[ 33 ]. On the other hand, denying LT to a patient with AIH and LF who is unlikely to respond to corticosteroids means condemning them to a certain death, which is unacceptable, especially since post-transplant survival for AIH is excellent [estimated 5-year survival probability after first LT is 0. The contentious issue thus is how best to stratify patients with AIH and LF into likely responders and non-responders to corticosteroids as soon as possible after hospitalization; hence optimizing their management.
Furthermore, in our study, responders to corticosteroids were more likely to have either an improvement or stabilization in bilirubin and INR within 3.
Surprisingly, in our study, the presence of cirrhosis was more likely was associated with response to corticosteroids[ 7 ]. Although the impact of cirrhosis on the natural history of AIH remains controversial[ 27 , 28 , 35 , 36 ], it is likely that this group has long-standing indolent disease that progresses to cirrhosis, with LF representing an acute relapse of AIH[ 37 ]. This is in contrast with the study of Ichai et al[ 25 ], in which absence of significant hepatic fibrosis in all the patients indicated a de novo fulminant disease process.
Whether steroids increase the risk of septic complications in patients with severe liver disease is subject to an ongoing debate.
The issue becomes even more contentious in the presence of LF because in itself that has been associated with an increased risk of bacterial and fungal infections[ 25 , 38 , 39 ]. This increased propensity for sepsis is further aggravated in the post-transplant setting due to use of immunosuppression. Therefore, not surprisingly, sepsis with or without multiorgan failure, accounts for almost one-third of all deaths in patients undergoing LT for LF, and is the most common cause of mortality in this cohort[ 40 ].
Hepatitis A or B infection uncommon to occur this way Blockage of blood supply to the liver Poisoning by different toxins or medicines Constipation Upper gastrointestinal bleeding People with severe liver damage often suffer from HE. Common causes of chronic liver disease are: Less body fluids dehydration Eating too much protein Low potassium or sodium levels Bleeding from the intestines, stomach, or food pipe esophagus Infections Kidney problems Low oxygen levels in the body Shunt placement or complications Surgery Narcotic pain or sedative medicines Disorders that can appear similar to HE may include: Alcohol intoxication Alcohol withdrawal Bleeding under the skull Brain disorder caused by lack of vitamin B1 In some cases, HE is a short-term problem that can be corrected.
Early symptoms may be mild and include: Breath with a musty or sweet odor Changes in sleep patterns Changes in thinking Mild confusion Forgetfulness Personality or mood changes Poor concentration and judgment Worsening of handwriting or loss of other small hand movements Severe symptoms may include: Abnormal movements or shaking of hands or arms Agitation, excitement, or seizures occur rarely Disorientation Drowsiness or confusion Behavior or personality changes Slurred speech Slowed or sluggish movement People with HE can become unconscious, unresponsive, and possibly enter a coma.
People are often not able to care for themselves because of these symptoms. Signs of nervous system changes may include: Shaking of the hands "flapping tremor" when trying to hold arms in front of the body and lift the hands Problems with thinking and doing mental tasks Signs of liver disease , such as yellow skin and eyes jaundice and fluid collection in the abdomen ascites Musty odor to the breath and urine Tests done may include: Treatment of HE depends upon the cause.
If changes in brain function are severe, a hospital stay may be needed. Bleeding in the digestive tract must be stopped. Infections, kidney failure, and changes in sodium and potassium levels need to be treated. Medicines given may include: Neomycin and rifaximin also reduce the amount of ammonia made in the intestines. If the HE improves while taking rifaximin, it should be continued indefinitely. Any sedatives, tranquilizers, and any other medicines that are broken down by the liver.
Medicines containing ammonium including certain antacids Your health care provider may suggest other medicines and treatments. When to Contact a Medical Professional.
Autoimmune hepatitis rarely presents as fulminant hepatic failure. Approximately one Ascites and hepatic encephalopathy also may ensue. To review diagnosis and management of autoimmune hepatitis Autoimmune Hepatitis (AIH). •. Type I . Treatment and prevention of hepatic encephalopathy. Loss of brain function occurs when the liver is unable to remove toxins from the blood. This is called hepatic encephalopathy (HE). Severe hepatitis B or C infection; Alcohol abuse · Autoimmune hepatitis; Bile duct disorders.