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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 While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment.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.
Treatment with antiviral medication is recommended in all people with proven chronic hepatitis C who are not at high risk of dying from other causes. People with the highest complication risk should be treated first, with the risk of complications based on the degree of liver scarring. The initial recommended treatment depends on the type of hepatitis C virus and whether or not a person has cirrhosis.
- HCV genotype 1a (no cirrhosis): 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Sofosbuvir with either daclatasvir or simeprevir may also be used.
- HCV genotype 1a (with cirrhosis): 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir.
- HCV genotype 1b (no cirrhosis): 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Sofosbuvir with either daclatasvir or simeprevir may also be used.
- HCV genotype 1b (with cirrhosis): 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir.
- HCV genotype 2 (with or without cirrhosis): 12 weeks of sofosbuvir/velpatasvir.
- HCV genotype 3 (no cirrhosis): 12 weeks of sofosbuvir/velpatasvir or daclatasvir and sofosbuvir.
- HCV genotype 3 (with cirrhosis): 12 weeks of sofosbuvir/velpatasvir or 24 weeks of daclatasvir and sofosbuvir.
- HCV genotype 4 (with and without cirrhosis): 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir.
- HCV genotype 5 or 6: 12 weeks of sofosbuvir/velpatasvir or ledipasvir/sofosbuvir.
Chronic infection can be cured about 95% of the time with recommended treatment in 2017. Getting access to these treatments however can be expensive. The combination of sofosbuvir, velpatasvir, and voxilaprevir may be used in those who have previously been treated with sofosbuvir or other drugs that inhibit NS5A and were not cured.
Prior to 2011, treatments consisted of a combination of pegylated interferon alpha and ribavirin for a period of 24 or 48 weeks, depending on HCV genotype. This produces cure rates of between 70 and 80% for genotype 2 and 3, respectively, and 45 to 70% for genotypes 1 and 4. Adverse effects with these treatments were common, with half of people getting flu like symptoms and a third experiencing emotional problems. Treatment during the first six months is more effective than once has become chronic.
In terms of treatment, ribavirin is not registered for hepatitis E treatment, though off-label experience for treating chronic hepatitis E with this compound exists. The use of low doses of ribavirin over a three-month period has been associated with viral clearance in about two-thirds of chronic cases. Other possible treatments include pegylated interferon or a combination of ribavirin and pegylated interferon. In general, chronic HEV infection is associated with immunosuppressive therapies, but remarkably little is known about how different immunosuppressants affect HEV infection. In individuals with solid-organ transplantation, viral clearance can be achieved by temporal reduction of the level of immunosuppression.
Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis.
Acute infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype. Treatment duration when medication is taken by mouth, however, is more variable and usually longer than one year.
Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2008, there are seven medications licensed for the treatment of infection in the United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude), and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a (Pegasys). In 2015 the World Health Organization recommended tenofovir or entecavir as first-line agents. Those with current cirrhosis are in most need of treatment.
The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of the genotype of the infecting virus or the person's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.
Several alternative therapies are claimed by their proponents to be helpful for including milk thistle, ginseng, and colloidal silver. However, no alternative therapy has been shown to improve outcomes in , and no evidence exists that alternative therapies have any effect on the virus at all.
No specific treatment for hepatitis A is known. Recovery from symptoms following infection may take several weeks or months. Therapy is aimed at maintaining comfort and adequate nutritional balance, including replacement of fluids lost from vomiting and diarrhoea.
There is currently no specific therapy. Intravenous fluids and treatment of the hepatic encephalopathy may help. Increasing dietary levels of branched chain amino acids and feeding low protein diets can help signs of hepatic encephalopathy, which is often accomplished by feeding small amounts of grain and/or beet pulp, and removing high-protein feedstuffs such as alfalfa hay. Grazing on non-legume grass may be acceptable if it is late summer or fall, although the horse should only be permitted to eat in the evening so as to avoid photosensitization. Due to the risk of gastric impaction, stomach size should be monitored.
Sedation is minimized and used only to control behavior that could lead to injury of the animal and to allow therapeutic procedures, and should preferably involve a sedative other than a benzodiazepine. Stressing the animal should be avoided if at all possible. Plasma transfusions may be needed if spontaneous bleeding occurs, to replace clotting factors. Antibiotics are sometimes prescribed to prevent bacterial translocation from the intestines. Antioxidants such as vitamin E, B-complex vitamins, and acetylcysteine may be given. High blood ammonia is often treated with oral neomycin, often in conjunction with lactulose, metronidazole and probiotics, to decrease production and absorption of ammonia from the gastrointestinal tract.
In assisted reproductive technology, sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of transmission from mother to child with IVF is no different from the risk in spontaneous conception.
Those at high risk of infection should be tested as there is effective treatment for those who have the disease. Groups that screening is recommended for include those who have not been vaccinated and one of the following: people from areas of the world where hepatitis B occurs in more than 2%, those with HIV, intravenous drug users, men who have sex with men, and those who live with someone with hepatitis B.
The vaccine for hepatitis B protects against hepatitis D virus because of the latter's dependence on the presence of hepatitis B virus for it to replicate.
Latest evidence suggests that Pegylated interferon alpha is effective in reducing the viral load and the effect of the disease during the time the drug is given, but the benefit generally stops if the drug is discontinued. The efficiency of the pegylated interferon treatment does not usually exceed ~20%.
The drug myrcludex B, which inhibits virus entry into hepatocytes, is in clinical trials .
Treatment may involve the prescription of immunosuppressive glucocorticoids such as prednisone, with or without azathioprine, and remission can be achieved in up to 60–80% of cases, although many will eventually experience a relapse. Budesonide has been shown to be more effective in inducing remission than prednisone, and result in fewer adverse effects. Those with autoimmune hepatitis who do not respond to glucocorticoids and azathioprine may be given other immunosuppressives like mycophenolate, ciclosporin, tacrolimus, methotrexate, etc. Liver transplantation may be required if patients do not respond to drug therapy or when patients present with fulminant liver failure.
There is no specific treatment for neonatal hepatitis. Vitamin supplements are usually prescribed and many infants are given phenobarbital, a drug used to control seizures, but which also stimulates the liver to excrete additional bile. Formulas containing more easily digested fats are also given to the infant.
Neonatal hepatitis caused by the hepatitis A virus also usually resolves itself within six months, but cases that are the result of infection with the hepatitis B or hepatitis C viruses most likely will result in chronic liver disease. Infants who develop cirrhosis ultimately will need a liver transplant.
In the United States in 1991, the mortality rate for hepatitis A was estimated to be 0.015% for the general population, but ranged up to 1.8 -2.1 % for those aged 50 and over which were hospitalized with icteric hepatitis. The risk of death from acute liver failure following HAV infection increases with age and when the person has underlying chronic liver disease.
Young children who are infected with hepatitis A typically have a milder form of the disease, usually lasting 1–3 weeks, whereas adults tend to experience a much more severe form of the disease.
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.
There has been no specific drug therapy developed for hepatitis, with the exception of hepatitis C. Patients are advised to rest in the early stages of the illness, and to eat small, high-calorie, high-protein meals in order to battle anorexia. Larger meals are more easily tolerated in the morning, for patients often experience nausea later in the day. Although high-protein meals are recommended, protein intake should be reduced if signs of precoma — lethargy, confusion, and mental changes — develop.
In acute viral hepatitis, hospitalization is usually required only for patients with severe symptoms (severe nausea, vomiting, change in mental status, and PT greater than 3 seconds above normal) or complications. If the patient experiences continuous vomiting and is unable to maintain oral intake, parenteral nutrition may be required.
In order to relieve nausea and also prevent vomiting, antiemetics (diphenhydramine or prochlorperazine) may be given 30 minutes before meals. However, phenothiazines have a cholestatic effect and should be avoided. The resin cholestyramine may be given only for severe pruritus.
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.
A vaccine based on recombinant viral proteins was developed in the 1990s and tested in a high-risk population (in Nepal) in 2001. The vaccine appeared to be effective and safe, but development was stopped for lack of profitability, since hepatitis E is rare in developed countries. No hepatitis E vaccine is licensed for use in the United States.
Although other HEV vaccine trials have been successful, these vaccines have not yet been produced or made available to susceptible populations. The exception is China; after more than a year of scrutiny and inspection by China's State Food and Drug Administration (SFDA), a hepatitis E vaccine developed by Chinese scientists was available at the end of 2012. The vaccine—called HEV 239 by its developer Xiamen Innovax Biotech—was approved for prevention of hepatitis E in 2012 by the Chinese Ministry of Science and Technology, following a controlled trial on 100,000+ people from Jiangsu Province where none of those vaccinated became infected during a 12-month period, compared to 15 in the group given placebo. The first vaccine batches came out of Innovax' factory in late October 2012, to be sold to Chinese distributors.
Due to the lack of evidence, WHO did not make a recommendation regarding routine use of the HEV 239 vaccine. National authorities may however, decide to use the vaccine based on the local epidemiology.
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.
The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity: Troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone, ximelagatran and pemoline.
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.
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.
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.
This depends on the degree of hepatocellular necrosis that has occurred. Decreases in the SDH and prothrombin time along with improvement in appetite are the best positive predictive indicators of recovery. GGT may remain elevated for weeks even if the horse is recovering. Horses that survive for greater than one week and that continue to eat usually recover. Cases with rapid progression of clinical signs, uncontrollable encephalopathy, haemorrhage or haemolysis have a poor prognosis. Horses that display clinical signs have a mortality rate of 50–90%.
There is no specific treatment for the condition.
Control may rely on boosting bird immunity, preventing group mixing and faecal spreading.
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.