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.

Not drinking further alcohol is the most important part of treatment. People with chronic HCV infection should abstain from any alcohol intake, due to the risk for rapid acceleration of liver disease.

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.

Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation; their role in preventing encephalopathy is limited.

Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with chelation therapy (for example, penicillamine) to remove the copper.

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).

Gradual weight loss may improve the process in obese patients; rapid loss may worsen NAFLD. Specifically, walking or some form of aerobic exercise at least 30–45 minutes daily is recommended. The negative effects of rapid weight loss are controversial: the results of a meta-analysis showed that the risk of progression is very low.

Treatment of NAFLD typically involves counseling to improve nutrition and consequently body weight and composition. Diet changes have shown significant histological improvement. Specifically, avoiding food containing high-fructose corn syrup and trans-fats is recommended. A systematic review and meta-analysis found that omega-3 fatty acid supplementation in those with NAFLD/NASH using doses approaching or higher than 1 gram daily (median dose 4 grams/day with median duration 6 months treatment) has been associated with improvements in liver fat. The best dose of omega-3 fatty acids for individuals with NAFLD/NASH is unclear.

Epidemiological data have suggested that coffee consumption may be associated with a decreased incidence of NAFLD and may reduce the risk of liver fibrosis in those who already have NAFLD/NASH. Olive oil consumption, as part of the Mediterranean diet, is also a reasonable dietary intervention; the optimal dose of olive oil supplementation for people with NAFLD/NASH has not been well-established. Few studies have been performed to evaluate the respective impact of a diet rich in avocados, red wine, tree nuts, or tea in people with NAFLD/NASH. However, limited evidence suggests that avocados may improve other areas of cardiovascular health (i.e., lipid profile) and their addition to a balanced diet is reasonable. Red wine consumption (in modest amounts) is likely safe and may improve insulin resistance but definitive studies are lacking.

The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including corticosteroids, interferon, antivirals, bile acids or other drugs. Supportive therapy for complications of cirrhosis include diuretics, albumin, vitamin K, blood products, antibiotics and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.

Many herbal and antioxidant remedies have been advocated for chronic liver disease but the evidence is not conclusive. Some support may be found in the orthodox medical use of two of these: N-acetyl cysteine (NAC), is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle (Silybum marianum) or its derivative silibinin are used in liver poisoning from certain mushrooms, notably amanita phalloides, although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang, chaparral, comfrey, germander, greater celandine, kava, mistletoe, pennyroyal, skull cap and valerian.

Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:

- By using steroid-based drugs in autoimmune hepatitis.

- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.

- Wilson’s disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.

- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.

The treatment of fatty liver depends on its cause, and, in general, treating the underlying cause will reverse the process of steatosis if implemented at an early stage. Two known causes of fatty liver disease are an excess consumption of alcohol and a prolonged diet containing foods with a high proportion of calories coming from lipids. For the patients with non-alcoholic fatty liver disease with pure steatosis and no evidence of inflammation, a gradual weight loss is often the only recommendation. In more serious cases, medications that decrease insulin resistance, hyperlipidemia, and those that induce weight loss have been shown to improve liver function.

For advanced patients with non-alcoholic steatohepatitis (NASH), there are no currently available therapies.

Up to 10% of people with cirrhotic alcoholic FLD will develop hepatocellular carcinoma. The overall incidence of liver cancer in nonalcoholic FLD has not yet been quantified, but the association is well-established.

Bariatric surgery, while not currently recommended as a treatment for fatty liver disease (FLD) alone, has been shown to revert FLD and advanced steatohepatitis in over 90% of people who have undergone this surgery for the treatment of obesity.

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.

In patients with grade I or II encephalopathy, enteral feeding should be initiated early. Parenteral nutrition should be used only if enteral feeding is contraindicated as it increases the risk of infection. Severe restriction of protein is not beneficial; 60 g/day of protein is generally reasonable. Fluid replacement with colloid (e.g. albumin) is preferred rather than crystalloid (e.g. saline); all solutions should contain dextrose to maintain euglycemia. Multiple electrolyte abnormalities are common in ALF. Correction of hypokalemia is essential as hypokalemia increases the kidneys' ammonia production, potentially exacerbating encephalopathy. Hypophosphatemia is especially common in patients with acetaminophen-induced ALF and in those with intact renal function. Hypoglycemia occurs in many patients with ALF and is often due to depletion of hepatic glycogen stores and impaired gluconeogenesis. Plasma glucose concentration should be monitored and hypertonic glucose administered as needed.

Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. There have been 7 drug treatments approved to date in the United States:

- Injectable interferon alpha was the first therapy approved for chronic hepatitis B. It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication. These include long-acting interferon bound to polyethylene glycol (pegylated interferon) and the oral nucleoside analogues.

- Pegylated interferon (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500-8,700 for the oral medications; however, its treatment duration is 48 weeks as opposed to the oral antivirals, which require indefinite treatment for most patients (minimum 1 year). PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis.

- Lamivudine was the first approved oral nucleoside analogue. While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment. However, it is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients, consolidation therapy is recommended to be extended to at least a year. All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well-tolerated. Many patients develop resistance, which is correlated with longer treatment duration. If this occurs, an additional antiviral is added. Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen.

- Adefovir dipivoxil, a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy.

- Entecavir is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive.

- Telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone.

- Tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection. It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.

First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference. Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, HBeAg positive or negative status, ALT levels, and in certain cases, family history of HCC and liver biopsy. In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x10 IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level. In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable. Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir.

Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration. Hospitalization may be required for particularly severe cases or for pregnant women.

"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%.

Non-alcoholic steatohepatitis is fatty liver disease due to causes other than alcohol. No pharmacological treatment has received approval as of 2015 for NASH. Some studies suggest diet, exercise, and antiglycemic drugs may alter the course of the disease. General recommendations include improving metabolic risk factors and reducing alcohol intake. NASH was first described in 1980 in a series of patients of the Mayo Clinic. Its relevance and high prevalence were recognized mainly in the 1990s. Some think NASH is a diagnosis of exclusion, and many cases may in fact be due to other causes.

Early diagnosis is vital as the late effects of iron accumulation can be wholly prevented by periodic phlebotomies (by venesection) comparable in volume to blood donations. Initiation of treatment is recommended when ferritin levels reach 500 milligrams per litre.

Phlebotomy (or bloodletting) is usually done at a weekly interval until ferritin levels are less than 50 milligrams per litre. In order to prevent iron reaccumulation, subsequent phlebotomies are normally carried out approximately once every three to four months for males, and twice a year for females.

Where venesection is not possible, long-term administration of desferrioxamine mesylate is useful. Desferrioxamine is an iron-chelating compound, and excretion induced by desferrioxamine is enhanced by administration of Vitamin C. It cannot be used during pregnancy or breast-feeding due to risk of defects in the child.

Treatment of hepatocellular carcinoma varies by the stage of disease, a person's likelihood to tolerate surgery, and availability of liver transplant:

1. Curative intention: for limited disease, when the cancer is limited to one or more areas of within the liver, surgically removing the malignant cells may be curative. This may be accomplished by resection the affected portion of the liver (partial hepatectomy) or in some cases by orthotopic liver transplantation of the entire organ.

2. "Bridging" intention: for limited disease which qualifies for potential liver transplantation, the person may undergo targeted treatment of some or all of the known tumor while waiting for a donor organ to become available.

3. "Downstaging" intention: for moderately advanced disease which has not spread beyond the liver, but is too advanced to qualify for curative treatment. The person may be treated by targeted therapies in order to reduce the size or number of active tumors, with the goal of once again qualifying for liver transplant after this treatment.

4. Palliative intention: for more advanced disease, including spread of cancer beyond the liver or in persons who may not tolerate surgery, treatment intended to decrease symptoms of disease and maximize duration of survival.

Loco-regional therapy (also referred to as liver-directed therapy) refers to any one of several minimally-invasive treatment techniques to focally target HCC within the liver. These procedures are alternatives to surgery, and may be considered in combination with other strategies, such as a later liver transplantation. Generally, these treatment procedures are performed by interventional radiologists or surgeons, in coordination with a medical oncologist. Loco-regional therapy may refer to either percutaneous therapies (e.g. cryoablation), or arterial catheter-based therapies (chemoembolization or radioembolization).

Treatment for hemosiderin focuses on limiting the effects of the underlying disease leading to continued deposition. In hemochromatosis, this entails frequent phlebotomy granulomatosis, immune suppression is required. Limiting blood transfusions and institution of iron chelation therapy when iron overload is detected are important when managing sickle-cell anemia and other chronic hemolytic anemias.

Surgical removal of the tumor is associated with better cancer prognosis, but only 10-15% of patients are suitable for surgical resection due to the extent of disease or poor liver function. Surgery is only considered if the entire tumor can be safely removed while preserving sufficient functional liver to maintain normal physiology. Thus, pre-operative imaging assessment is critical in order to determine both the extent of HCC and to estimate the amount of residual liver remaining after surgery. In order to maintain liver function, residual liver volume should exceed 25% of total liver volume in a non-cirrhotic liver, greater than 40% in a cirrhotic liver. Surgery on diseased or cirrhotic livers is generally associated with higher morbidity and mortality. The overall recurrence rate after resection is 50-60%. The Singapore Liver Cancer Recurrence (SLICER) score can be used to estimate risk of recurrence after surgery.

In the United States there are four approved medications for alcoholism: disulfiram, two forms of naltrexone, and acamprosate. Several other drugs are also used and many are under investigation.

- Benzodiazepines, while useful in the management of acute alcohol withdrawal, if used long-term can cause a worse outcome in alcoholism. Alcoholics on chronic benzodiazepines have a lower rate of achieving abstinence from alcohol than those not taking benzodiazepines. This class of drugs is commonly prescribed to alcoholics for insomnia or anxiety management. Initiating prescriptions of benzodiazepines or sedative-hypnotics in individuals in recovery has a high rate of relapse with one author reporting more than a quarter of people relapsed after being prescribed sedative-hypnotics. Those who are long-term users of benzodiazepines should not be withdrawn rapidly, as severe anxiety and panic may develop, which are known risk factors for relapse into alcohol abuse. Taper regimes of 6–12 months have been found to be the most successful, with reduced intensity of withdrawal.

- Acamprosate may stabilise the brain chemistry that is altered due to alcohol dependence via antagonising the actions of glutamate, a neurotransmitter which is hyperactive in the post-withdrawal phase. By reducing excessive NMDA activity which occurs at the onset of alcohol withdrawal, acamprosate can reduce or prevent alcohol withdrawal related neurotoxicity. Acamprosate reduces the risk of relapse amongst alcohol dependent persons.

- Disulfiram (Antabuse) prevents the elimination of acetaldehyde, a chemical the body produces when breaking down ethanol. Acetaldehyde itself is the cause of many hangover symptoms from alcohol use. The overall effect is severe discomfort when alcohol is ingested: an extremely fast-acting and long-lasting uncomfortable hangover. This discourages an alcoholic from drinking in significant amounts while they take the medicine.

- Naltrexone is a competitive antagonist for opioid receptors, effectively blocking the effects of endorphins and opioids. Naltrexone is used to decrease cravings for alcohol and encourage abstinence. Alcohol causes the body to release endorphins, which in turn release dopamine and activate the reward pathways; hence when naltrexone is in the body there is a reduction in the pleasurable effects from consuming alcohol. Evidence supports a reduced risk of relapse among alcohol dependent persons and a decrease in excessive drinking. Nalmefene also appears effective and works by a similar manner.

- Calcium carbimide works in the same way as disulfiram; it has an advantage in that the occasional adverse effects of disulfiram, hepatotoxicity and drowsiness, do not occur with calcium carbimide.

The Sinclair method is a method of using naltrexone or another opioid antagonists to treat alcoholism by having the person take the medication about an hour before they drink alcohol, and only then. The medication blocks the positive reinforcement effects of ethanol and hopefully allows the person to stop drinking or drink less.

Evidence does not support the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), antipsychotics, or gabapentin.

Alcoholic hepatitis is hepatitis (inflammation of the liver) due to excessive intake of alcohol. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Signs and symptoms of alcoholic hepatitis include jaundice, ascites (fluid accumulation in the abdominal cavity), fatigue and hepatic encephalopathy (brain dysfunction due to liver failure). Mild cases are self-limiting, but severe cases have a high risk of death. Severe cases may be treated with glucocorticoids.

Alcoholics may also require treatment for other psychotropic drug addictions and drug dependences. The most common dual dependence syndrome with alcohol dependence is benzodiazepine dependence, with studies showing 10–20 percent of alcohol-dependent individuals had problems of dependence and/or misuse problems of benzodiazepine drugs such as valium or clonazopam. These drugs are, like alcohol, depressants. Benzodiazepines may be used legally, if they are prescribed by doctors for anxiety problems or other mood disorders, or they may be purchased as illegal drugs "on the street" through illicit channels. Benzodiazepine use increases cravings for alcohol and the volume of alcohol consumed by problem drinkers. Benzodiazepine dependency requires careful reduction in dosage to avoid benzodiazepine withdrawal syndrome and other health consequences. Dependence on other sedative-hypnotics such as zolpidem and zopiclone as well as opiates and illegal drugs is common in alcoholics. Alcohol itself is a sedative-hypnotic and is cross-tolerant with other sedative-hypnotics such as barbiturates, benzodiazepines and nonbenzodiazepines. Dependence upon and withdrawal from sedative-hypnotics can be medically severe and, as with alcohol withdrawal, there is a risk of psychosis or seizures if not managed properly.