Lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. They are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (NH) ions, and increase transit of bowel content through the gut. Doses of 15-30 ml are administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool pH of <6.0. Lactulose may also be given by enema, especially if encephalopathy is severe. More commonly, phosphate enemas are used. 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. Lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy. Side effects of lactulose and lactitol include the possibility of diarrhea, bloating, flatulence, and nausea. In acute liver failure, it is unclear whether lactulose is beneficial. 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. It is a nonabsorbable antibiotic from the rifamycin class. 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. Rifaximin is more expensive than lactulose, but the cost may be offset by reduced hospital admissions for encephalopathy.

The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy. The rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. 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.

Patients with grade I–II encephalopathy should be transferred to a liver transplant facility and listed for transplantation. Consider a brain computed tomography (CT) scan to rule out other causes of altered or impaired mental status. Stimulation and overhydration can cause elevations in intracranial pressure (ICP) and should be avoided. Unmanageable agitation may be treated with short-acting benzodiazepines in small doses. Lactulose can be considered at this stage. A preliminary report from the ALFSG on 117 patients suggests that use of lactulose in the first 7 days after diagnosis is associated with a small increase in survival time, but with no difference in severity of encephalopathy or in the overall outcome. For patients who progress to grade III–IV encephalopathy, intubation for airway protection is generally required. Many centers use propofol for sedation because it may reduce cerebral blood. The head of the bed should be elevated to 30 degrees, and electrolytes, blood gasses, glucose, and neurologic status monitored frequently.

Impaired liver synthesis of clotting factors, low-grade fibrinolysis, and intravascular coagulation are typical of ALF. Thrombocytopenia is common and may also be dysfunctional. Replacement therapy is recommended only in the setting of bleeding or prior to an invasive procedure. Vitamin K can be given to treat an abnormal prothrombin time, regardless of whether there is poor nutritional status. Administration of recombinant factor VIIa has shown promise; however, this treatment approach requires further study. The use of gastrointestinal hemorrhage prophylaxis with a histamine-2 (H2) blocker, proton pump inhibitor, or sucralfate is recommended.

A 2006 Cochrane review did not find evidence sufficient for the use of androgenic anabolic steroids. Corticosteroids are sometimes used; however, this is recommended only when severe liver inflammation is present.

Sylimarin has been investigated as a possible treatment, with ambiguous results. One review claimed benefit for S-adenosyl methionine in disease models.

The effects of anti–tumor necrosis factor medications such as infliximab and etanercept are unclear and possibly harmful. Evidence is unclear for pentoxifylline. Propylthiouracil may result in harm.

Evidence does not support supplemental nutrition in liver disease.

Although in rare cases liver cirrhosis is reversible, the disease process remains mostly irreversible. Liver transplantation remains the only definitive therapy. Today, survival after liver transplantation is similar for people with ALD and non-ALD. The requirements for transplant listing are the same as those for other types of liver disease, except for a 6-month sobriety prerequisite along with psychiatric evaluation and rehabilitation assistance (i.e., Alcoholics Anonymous). Specific requirements vary among the transplant centers. Relapse to alcohol use after transplant listing results in delisting. Re-listing is possible in many institutions, but only after 3–6 months of sobriety. There are limited data on transplant survival in patients transplanted for acute alcoholic hepatitis, but it is believed to be similar to that in nonacute ALD, non-ALD, and alcoholic hepatitis with MDF less than 32.

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). Diuretics may be necessary to suppress ascites. Diuretic options for inpatient treatment include aldosterone antagonists (spironolactone) and loop diuretics. Aldosterone antagonists are preferred for people who can take oral medications and are not in need of an urgent volume reduction. Loop diuretics can be added as additional therapy.

If a rapid reduction of volume is required, paracentesis is the preferred option. This procedure requires the insertion of a plastic tube into the peritoneal cavity. Human albumin solution is usually given to prevent complications from the rapid volume reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy.

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical risk factors in the recipient. In the United States, the MELD score is used to prioritize patients for transplantation. Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus).

Clinical practice guidelines by the American College of Gastroenterology have recommended corticosteroid treatment. Patients should be risk stratified using a MELD Score or Child-Pugh score.

- Corticosteroids: These guidelines suggest that patients with a modified Maddrey's discriminant function score > 32 or hepatic encephalopathy should be considered for treatment with prednisolone 40 mg daily for four weeks followed by a taper. Models such as the Lille Model can be used to monitor for improvement or to consider alternative treatment.

- Pentoxifylline: A randomized controlled trial found that among patients with a discriminant function score > 32 and at least one of the following symptoms (a palpable, tender enlarged liver, fever, high white blood cell count, hepatic encephalopathy, or hepatic systolic bruit), 4.6 patients must be treated with pentoxifylline for 4 weeks to prevent one patient from dying. Subsequent trials have suggested that pentoxifylline may be superior to prednisolone in the management of acute alcoholic hepatitis with discriminant function score >32. Advantage of pentoxifylline over prednisolone was better tolerability, lesser side effects, with decreased occurrence of renal dysfunction in patients receiving pentoxifylline.

- Potential for combined therapy: A large prospective study of over 1000 patients investigated whether prednisolone and pentoxifylline produced benefits when used alone or in combination. Pentoxifylline did not improve survival alone or in combination. Prednisolone gave a small reduction in mortality at 28 days but this did not reach significance, and there were no improvements in outcomes at 90 days or 1 year.

Acute fatty liver of pregnancy is best treated in a centre with expertise in hepatology, high-risk obstetrics, maternal-fetal medicine and neonatology. The physicians who treat this condition will often consult with experts in liver transplantation in severe cases. Admission to the intensive care unit is recommended.

Initial treatment involves supportive management with intravenous fluids, intravenous glucose and blood products, including fresh frozen plasma and cryoprecipitate to correct DIC. The foetus should be monitored with cardiotocography. After the mother is stabilized, arrangements are usually made for delivery. This may occur vaginally, but, in cases of severe bleeding or compromise of the mother's status, a caesarian section may be needed. Often AFLP is not diagnosed until the mother and baby are in trouble, so it is most likely that an emergency C-section is needed.

The complications of acute fatty liver of pregnancy may require treatment after delivery, especially if pancreatitis occurs. Liver transplantation is rarely required for treatment of the condition, but may be needed for mothers with severe DIC, those with rupture of the liver, or those with severe encephalopathy.

Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some patients. In severe cases, dialysis or organ replacement surgery may be needed.

Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in patients with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.

The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity: Troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone, ximelagatran and pemoline.

In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In acetaminophen toxicity, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.

An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hy's Law). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.

The initial aim of treatment in hypertensive crises is to rapidly lower the diastolic pressure to about 100 to 105 mmHg; this goal should be achieved within two to six hours, with the maximum initial fall in BP not exceeding 25 percent of the presenting value. This level of BP control will allow gradual healing of the necrotizing vascular lesions. More aggressive hypotensive therapy is both unnecessary and may reduce the blood pressure below the autoregulatory range, possibly leading to ischemic events (such as stroke or coronary disease).

Once the BP is controlled, the person should be switched to medication by mouth, with the diastolic pressure being gradually reduced to 85 to 90 mmHg over two to three months. The initial reduction to a diastolic pressure of approximately 100 mmHg is often associated with a modest worsening of renal function; this change, however, is typically transient as the vascular disease tends to resolve and renal perfusion improves over one to three months. Antihypertensive therapy should not be withheld in this setting unless there has been an excessive reduction in BP. A change in medication, however, is indicated if the decline in renal function is temporally related to therapy with an angiotensin (ACE) converting enzyme inhibitor or angiotensin II receptor blocker, which can interfere with renal autoregulation and produce acute renal failure in patients with bilateral renal artery stenosis. (See "Renal effects of ACE inhibitors in hypertension".)

Several parenteral antihypertensive agents are most often used in the initial treatment of malignant hypertension.

- Nitroprusside – an arteriolar and venous dilator, given as an intravenous infusion. Nitroprusside acts within seconds and has a duration of action of only two to five minutes. Thus, hypotension can be easily reversed by temporarily discontinuing the infusion, providing an advantage over the drugs listed below. However, the potential for cyanide toxicity limits the prolonged use of nitroprusside, particularly in patients with renal insufficiency.

- Nicardipine – an arteriolar dilator, given as an intravenous infusion.

- Clevidipine – a short-acting dihydropyridine calcium channel blocker. It reduces blood pressure without affecting cardiac filling pressures or causing reflex tachycardia.

- Labetalol – an alpha- and beta-adrenergic blocker, given as an intravenous bolus or infusion. Bolus followed by infusion.

- Fenoldopam – a peripheral dopamine-1 receptor agonist, given as an intravenous infusion.

- Oral agents — A slower onset of action and an inability to control the degree of BP reduction has limited the use of oral antihypertensive agents in the therapy of hypertensive crises. They may, however, be useful when there is no rapid access to the parenteral medications described above. Both sublingual nifedipine and sublingual captopril can substantially lower the BP within 10 to 30 minutes in many patients. A more rapid response is seen when liquid nifedipine is swallowed.

The major risk with oral agents is ischemic symptoms (e.g., angina pectoris, myocardial infarction, or stroke) due to an excessive and uncontrolled hypotensive response. Thus, their use should generally be avoided in the treatment of hypertensive crises if more controllable drugs are available.

Treatment is directed largely to removing the cause, or, where that is impossible, to modifying its effects. Thus, therapy aimed at improving right heart function will also improve congestive hepatopathy. True nutmeg liver is usually secondary to left-sided heart failure causing congestive right heart failure, so treatment options are limited.

"Acute on chronic liver failure" is said to exist when someone with chronic liver disease develops features of liver failure. A number of underlying causes may precipitate this, such as alcohol misuse or infection. People with ACLF can be critically ill and require intensive care treatment, and occasionally a liver transplant. Mortality with treatment is 50%.

Treatment is mainly for the symptoms that toxic encephalopathy brings upon victims, varying depending on how severe the case is. Diet changes and nutritional supplements may help some patients. To reduce or halt seizures, anticonvulsants may be prescribed. Dialysis or organ replacement surgery may be needed in some severe cases.

Management of affected individuals consists of immediate removal from exposure to the toxic substance(s), treatment of the common clinical manifestation of depression if present, and counselling for the provision of life strategies to help cope with the potentially debilitating condition.

Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain. These permanent deficits can be considered a form of stable dementia. Some encephalopathies can be fatal.

In those with severe (tense) ascites, therapeutic paracentesis may be needed in addition to medical treatments listed above. As this may deplete serum albumin levels in the blood, albumin is generally administered intravenously in proportion to the amount of ascites removed.

Treatment generally includes supportive care including pain management and possibly diuretics. In the those severe disease due to a bone marrow transplant, defibrotide is a proposed treatment. It has been approved for use in severe cases in Europe and the United States. A placebo controlled trial, however, has not been done as of 2016.

Most symptoms will improve quickly if deficiencies are treated early. Memory disorder may be permanent.

In patients suspected of WE, thiamine treatment should be started immediately. Blood should be immediately taken to test for thiamine, other vitamins and minerals levels. Following this an immediate intravenous or intramuscular dose of thiamine should be administered two or three times daily. Thiamine administration is usually continued until clinical improvement ceases.

Considering the diversity of possible causes and several surprising symptomatologic presentations, and because there is low assumed risk of toxicity of thiamine, because the therapeutic response is often dramatic from the first day, some qualified authors indicate parenteral thiamine if WE is suspected, both as a resource for diagnosis and treatment. The diagnosis is highly supported by the response to parenteral thiamine, but is not sufficient to be excluded by the lack of it. Parenteral thiamine administration is associated with a very small risk of anaphylaxis.

Alcohol abusers may have poor dietary intakes of several vitamins, and impaired thiamine absorption, metabolism, and storage; they may thus require higher doses.

If glucose is given, such as in hypoglycaemic alcoholics, thiamine must be given concurrently. If this is not done, the glucose will rapidly consume the remaining thiamine reserves, exacerbating this condition.

The observation of edema in MR, and also the finding of inflation and macrophages in necropsied tissues, has led to successful administration of antiinflammatories.

Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease. In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.

Other supplements may also be needed, including: cobalamin, ascorbic acid, folic acid, nicotinamide, zinc, phosphorus (dicalcium phosphate) and in some cases taurine, especially suitable when there cardiocirculatory impairment.

Patient-guided nutrition is suggested. In patients with Wernicke-Korsakoff syndrome, even higher doses of parenteral thiamine are recommended. Concurrent toxic effects of alcohol should also be considered.

In the past, treatment options were limited to supportive medical therapy. Nowadays neonatal encephalopathy is treated using hypothermia therapy.

Both pharmacological (non-specific β-blockers, nitrate isosorbide mononitrate, vasopressin such as terlipressin) and endoscopic (banding ligation) treatment have similar results. TIPS (transjugular intrahepatic portosystemic shunting) is effective at reducing the rate of rebleeding.

The management of active variceal bleeding includes administering vasoactive drugs (somatostatin, octreotide), endoscopic banding ligation, balloon tamponade and TIPS.

Since salt restriction is the basic concept in treatment, and aldosterone is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be sought. Spironolactone (or other distal-tubule diuretics such as triamterene or amiloride) is the drug of choice since they block the aldosterone receptor in the collecting tubule. This choice has been confirmed in a randomized controlled trial. Diuretics for ascites should be dosed once per day. Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day).

40% of patients will respond to spironolactone. For nonresponders, a loop diuretic may also be added and generally, furosemide is added at a dose of 40 mg/day (max 160 mg/day), or alternatively (bumetanide or torasemide). The ratio of 100:40 reduces risks of potassium imbalance. Serum potassium level and renal function should be monitored closely while on these medications.

Monitoring diuresis: Diuresis can be monitored by weighing the patient daily. The goal is weight loss of no more than 1.0 kg/day for patients with both ascites and peripheral edema and no more than 0.5 kg/day for patients with ascites alone.

If daily weights cannot be obtained, diuretics can also be guided by the urinary sodium concentration. Dosage is increased until a negative sodium balance occurs. A random urine sodium-to-potassium ratio of > 1 is 90% sensitivity in predicting negative balance (> 78-mmol/day sodium excretion).

Diuretic resistance: Diuretic resistance can be predicted by giving 80 mg intravenous furosemide after 3 days without diuretics and on an 80 mEq sodium/day diet. The urinary sodium excretion over 8 hours < 50 mEq/8 hours predicts resistance.

If a patient exhibits a resistance to or poor response to diuretic therapy, ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid retention and congestion. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with diuretic resistance and may restore responsiveness to conventional doses of diuretics.

The management of ascites needs to be gradual to avoid sudden changes in systemic volume status which can precipitate hepatic encephalopathy, renal failure and death. The management includes salt restriction, diuretics (spironolactone), paracentesis, and transjugular intrahepatic portosystemic shunt.