Diagnostic uncertainty is probably the main reason so few trials of the treatment of autoimmune hepatitis have been performed. The earlier studies probably included some patients with hepatitis C who had autoimmune markers, since tests for hepatitis C virus were not available. With a better understanding of the pathophysiology of autoimmune hepatitis, a better definition of its target autoantigens, data on its immunoregulatory control, the availability of experimental models, and more accurate international diagnostic criteria, there are now firmer grounds for complementary studies of the natural history and treatment of autoimmune hepatitis.

        The short- and long-term efficacy of immunosuppression in patients with autoimmune hepatitis has been demonstrated unequivocally. In many cases, however, patients are not treated or treatment is begun too late because the diagnosis is missed. Autoimmune hepatitis has been considered a disease occurring predominantly in young women, but up to one third of the patients are men, and the disease can develop in all age groups. Although the clinical findings can vary substantially, a chronic fluctuating course is most common. Up to 40 percent of patients present with acute hepatitis, but either a fulminant presentation or a long subclinical course with only minimal elevations of liver enzymes may be seen. Almost all patients have autoantibodies, but only about two thirds have one of the classic autoimmune markers: antinuclear or anti-smooth-muscle antibodies. Tests for autoantibodies to soluble liver antigen, liver cytosol antigen, and the asialoglycoprotein receptor can help identify most cases.

        Hypergammaglobulinemia with a selective increase in serum IgG concentrations is a characteristic laboratory finding. In addition, HLA typing should be performed, since most patients are positive for HLA-B8, DR3, or DR4. If the findings are suggestive but not definitive, a prompt and complete response to immunosuppressive therapy may confirm the diagnosis. It is estimated that in Western countries 20 percent of patients with chronic hepatitis have autoimmune hepatitis, but many cases remain undiagnosed and thus untreated. Considerable progress in therapy could be made by considering the diagnosis earlier and more often.

        Initial therapy usually includes corticosteroids. Unless the disease is very mild, therapy should be started at about 1 mg of prednisone per kilogram of body weight daily. When serum aminotranferasc concentrations start to fall, the dose of prednisone should be tapered (at a rate of 10 mg per week, down to a dose of 30 mg per day, and then at a rate of 5 mg per week, down to a dose of 10 to 15 mg per day). Adding azathioprine can help keep the required dose of corticosteroids low. Azathioprine takes several weeks to work and should therefore be initiated as soon as the diagnosis is certain. Reports from King's College Hospital in London, in particular the report by Johns on et al. [October 1995] Journal, have helped define the role of azathioprine in the treatment of autoimmune hepatitis. The superiority of azathioprine over corticosteroids in maintaining remission and its efficacy as long-term maintenance therapy have been clearly shown by these studies.

        The rate of steroid withdrawal and the increased risk of cancer with long-term and high-dose azathioprine therapy in the study by Johnson et al. merit discussion. The researchers used 1 mg of azathioprine per kilogram together with prednisolone to induce remission and maintain it for one year. The dose of azathioprine was then doubled, and the prednisolone was withdrawn fairly rapidly in decrements of 2.5 mg per day every two weeks. Why was the dose of azathioprine doubled, and why was the prednisolone withdrawn over such a short time? More than half the patients in the study by Johnson et al. has arthralgias - presumably a symptom of corticosteroid withdrawal - which required the use of analgesic agents in about 40 percent of the patients. In our experience, withdrawal symptoms can generally be averted by tapering the prednisolone much more slowly (usually, 2.5 mg per day every three months).

        he relatively high dose of azathioprine was probably chosen because of concern about frequent relapses after the withdrawal of corticosteroids. After remission, the goal of therapy is to prevent relapses, with minimal side effects. The risks of osteoporosis and obesity, the most serious dose-dependent adverse effects of corticosteroids, have to be weighed against the risk of cancer due to relatively high doses of azathioprine. Many patients remain in remission with a dose of 50 mg of azathioprine per day. If this dose is insufficient, it may be safer to add 5 to 7.5 mg of prednisone per day than to increase the dose of azathioprine to 2 mg per kilogram per day. Of the 72 patients described by Johnson et al., 5, including 4 who died, had tumors. The risk of cancer is of particular concern in treating young patients, most of whom require lifelong immunosuppression.

        Other questions remain. First, can this experience in treating patients with the classic type of autoimmune hepatitis be extended to patients with autoantibodies to soluble liver antigen or liver-kidney-microsomal antigen or to the few patients with autoantibody-negative disease? We believe the answer is yes. Second, which drugs should be given to the minority of patients who cannot tolerate azathioprine or who do not have a complete remission? We have had favorable results with cyclophosphamide. Cyclosporine has been used successfully by other investigators. Third, should the goal always be complete biochemical remission, and should mild disease be treated? We believe the answer in both cases is yes, because fibrosis can develop rapidly, even serum aminotransferase concentrations are not very high. In the early clinical experience with this disease, many patients already had cirrhosis at the time of diagnosis. This is still true today.

        Finally, how long should patients be treated? Most patients with autoimmune hepatitis have to be treated throughout their lives, but 10 to 30 percent remain in remission without medications after a minimum of four years of maintenance therapy. Before immunosuppressive therapy is stopped, a liver biopsy should be performed to confirm that there is no inflammatory activity. After therapy has been stopped, patients should be monitored closely. Relapses usually occur during the first year but are still possible after many years.

[Source: Karl-Hermann Meyer, ZUM; Buschenfelde, M.D., Ph.D. Ansgar W. Lohse, M.D.]

Coauthored by David C Wolf, MD, FACP, FACG, Medical Director of Liver Transplantation, Associate Professor, Department of Internal Medicine, Division of Gastroenterology and Hepatobiliary Diseases, New York Medical College and Westchester Medical Center

http://www.emedicine.com/MED/topic366.htm    

Background:

 During the past 30 years, remarkable advances have occurred in our understanding of the epidemiology, natural history, and pathogenesis of chronic hepatitis. The development of viral serologic tests has permitted hepatologists to differentiate chronic viral hepatitis from other types of chronic liver disease, including autoimmune hepatitis. Autoimmune hepatitis is now accepted as a chronic disease of unknown cause, characterized by continuing hepatocellular inflammation and necrosis, which tends to progress to cirrhosis. Immune serum markers are frequently present, and the disease is often associated with other autoimmune diseases. Autoimmune hepatitis cannot be explained on the basis of chronic viral infection, alcohol consumption, or exposure to hepatotoxic medications or chemicals.

In 1950, Waldenstrom first described a form of chronic hepatitis in young women. This condition was characterized by cirrhosis, plasma cell infiltration of the liver, and marked hypergammaglobulinemia. Kunkel, in 1950, and Bearn, in 1956, described other features of the disease, including hepatosplenomegaly, jaundice, acne, hirsutism, cushingoid facies, pigmented abdominal striae, obesity, arthritis, and amenorrhea. In 1955, Joske first reported the association of the lupus erythematosus (LE) cell phenomenon in active chronic viral hepatitis. This association led to the introduction of the term lupoid hepatitis by Mackay and associates in 1956. Researchers currently know that no direct link exists between systemic lupus erythematosus (SLE) syndrome and autoimmune hepatitis; thus, lupoid hepatitis is not associated with SLE.

Autoimmune hepatitis now is recognized as a multisystem disorder that can occur in males and females of all ages. This condition can coexist with other liver diseases (eg, chronic viral hepatitis) and also may be triggered by certain viral infections (eg, hepatitis A) and chemicals (eg, minocycline).

The histopathologic description of autoimmune hepatitis has undergone several revisions over the years. In 1992, an international panel last codified the diagnostic criteria. The term autoimmune hepatitis was selected to replace terms like autoimmune liver disease and autoimmune chronic active hepatitis. The panel waived the requirement of 6 months of disease activity to establish chronicity, expanded the histologic spectrum to include lobular hepatitis, and reaffirmed the nonviral nature of the disease. The panel also designated incompatible histologic features, such as cholestatic histology, the presence of bile duct injury, and ductopenia.

The reasons for the aberrant HLA display are unclear. It may be initiated or triggered by genetic factors, viral infections (eg, acute hepatitis A or B, Epstein-Barr virus infection), and chemical agents (eg, interferon, melatonin, alpha methyldopa, oxyphenisatin, nitrofurantoin, tienilic acid). The asialoglycoprotein receptor and the cytochrome mono-oxygenase P-450 IID6 are proposed as the triggering autoantigens.

Some patients appear to be genetically susceptible to developing autoimmune hepatitis. This condition is associated with the complement allele C4AQO and with the HLA haplotypes B8, B14, DR3, DR4, and Dw3. C4A gene deletions are associated with the development of autoimmune hepatitis in younger patients. HLA DR3-positive patients are more likely than other patients to have aggressive disease, which is less responsive to medical therapy; these patients are younger than other patients at the time of their initial presentation. HLA DR4-positive patients are more likely to develop extrahepatic manifestations of their disease.

Evidence for an autoimmune pathogenesis includes the following:

• Hepatic histopathologic lesions composed predominantly of cytotoxic T cells and plasma cells

   

• Circulating autoantibodies (nuclear, smooth muscle, thyroid, liver kidney microsomal, soluble liver antigen, hepatic lectin

   

• Association with hypergammaglobulinemia and the presence of a rheumatoid factor

   

• Association with other autoimmune diseases

   

• Response to steroid and/or immunosuppressive therapy.

• The Hepatitis C Connection

Hepatitis C (HCV) has several important associations with autoimmune hepatitis. The prevalence rate of HCV infection in patients with autoimmune hepatitis is similar to that in the general population. This implies that HCV should not be an important factor in the etiology of autoimmune hepatitis; however, patients who are seropositive for anti–LKM-1 frequently are infected with HCV. These patients have predominant features of chronic viral hepatitis and frequently lack antibodies to P-450 IID6. Such patients respond to treatment with interferon. They should be distinguished from anti–LKM-1-positive patients who have a positive anti–P-450 IID6, are seronegative for anti-HCV, and are responsive to steroid therapy.

False-positive anti-HCV enzyme-linked immunoassay (ELISA) tests are described in the setting of hypergammaglobulinemia, including that observed in patients with autoimmune hepatitis. In patients with ANA and/or ASMA seropositivity and a positive anti-HCV, a false-positive reaction to HCV should be excluded by performing a test for HCV RNA, using the polymerase chain reaction (PCR). In general, patients with definite autoimmune hepatitis have median serum titers of ASMA and ANA of 1:160 and 1:320, respectively. In contrast, these titers may be in the range of 1:80 or less in patients with true chronic viral hepatitis.

Although autoimmune hepatitis and chronic HCV have similar histologic features, moderate-to-severe plasma cell infiltration of the portal tracts is more common in patients with autoimmune hepatitis. Portal lymphoid aggregates, steatosis, and bile duct damage are more common in patients with chronic HCV.

Lab Studies:
 

Treatment

Medical Care:

For more than 3 decades, prednisone and azathioprine have been the mainstays of drug therapy for patients with autoimmune hepatitis. Considerable variation in practice style exists when it comes to answering the following common clinical questions:

How high a dose of prednisone should be used when initiating therapy?

When should azathioprine be added to the patient's treatment regimen? When should a reduction in steroid dosing be considered?

How long should treatment continue beyond a patient's biochemical remission?

Should liver biopsy be performed in order to document histologic remission, prior to attempting to withdraw immunosuppression? Should patients receive life-long low-dose maintenance therapy with azathioprine?

Approximately 65% of patients respond to initial therapy and enter histological remission; however, 80% of these patients relapse after drug withdrawal.

Albert Czaja has recently published his treatment recommendations for autoimmune hepatitis, which are as follows:

	Absolute indication for treatment   Incapacitating symptoms   Relentless clinical progression   AST greater than 10 times normal   AST greater than 5 times normal and IgG greater than 2 times normal   Bridging necrosis on histology   Multilobular necrosis on histology
	Relative indication for treatment   Mild or no symptoms   AST 3-9 times normal   AST greater than 5 times normal and IgG less than 2 times normal   Periportal hepatitis on histology
	No indication   Asymptomatic   Previous intolerance to prednisone or azathioprine   AST less than 3 times normal   Severe cytopenia   Inactive cirrhosis or mild portal hepatitis on histology   Decompensated cirrhosis with variceal bleeding
	Czaja's guidelines for single-drug therapy are as follows:   Prednisone: 60 mg/d for 1 week, 40 mg/d for 1 week, 30 mg/d for 2 weeks, and 20 mg/d until reaching the treatment end point.   Recommendations for combination drug therapy are prednisone: 30 mg/d for 1 week, 20 mg/d for 1 week, 15 mg/d for 2 weeks, and 10 mg/d until reaching the treatment endpoint with azathioprine: 50 mg/d until reaching the treatment end point.

Treatment endpoints: Patients may achieve 1 of 4 treatment endpoints.   Complete remission is indicated by the absence of symptoms, a serum AST level less than 2 times normal, and histologic improvement to normal or minimal activity.   Treatment failure is defined as a deterioration in patient condition during therapy.   An incomplete patient response is defined as an improvement that is insufficient to satisfy remission criteria.   Drug toxicity may occur.   Patients with severe disease have a high short-term mortality rate if they fail to show normalization of at least 1 lab parameter or if pretreatment hyperbilirubinemia fails to improve during a 2-week treatment trial. In contrast, patients who improve by these parameters have an excellent immediate survival rate, and their treatment should be continued.   Histologic remission tends to lag behind clinical and lab remission by 3-6 months. Follow-up liver biopsies can optimize management by avoiding medication withdrawal in patients who are not yet in histologic remission.

Treatment results   Prednisone, alone or in combination with azathioprine, induces clinical, biochemical, and histologic remission in 65% of patients within 3 years. The average treatment interval until remission is 22 months. The fact that therapy improves survival rates is clear. The 10-year life expectancies for treated patients with and without cirrhosis at presentation are 89% and 90%, respectively.   Patients with a histologic diagnosis of cirrhosis still may respond well to therapy and should be offered treatment in an attempt to slow disease progression.

Treatment failures and incomplete responses   Nine percent of patients experience treatment failure with standard therapy. Treatment with high-dose prednisone (60 mg/d) alone or prednisone (30 mg/d) plus azathioprine (150 mg/d) is an alternative approach to therapy. Patients who are resistant to steroids can be treated with cyclosporine or tacrolimus.   Thirteen percent of patients improve with standard therapy but do not achieve remission criteria. A low-dose, long-term prednisone schedule, similar to that used after relapse (10 mg/d), is reasonable. The goal of therapy is to control disease activity on the lowest dose of medication possible. Azathioprine may help to serve as a steroid-sparing agent.   Patients should be referred for consideration of liver transplantation if they manifest signs of hepatic decompensation (eg, new onset of hypoalbuminemia or ascites).

Relapse   Relapse occurs in 50% of patients within 6 months of treatment withdrawal and in 80% of patients within 3 years of treatment. Reinstitution of the original treatment regimen usually induces another remission; however, relapse commonly recurs after a second attempt at terminating therapy. The major consequence of relapse and retreatment is the development of drug-related complications, which occurs in 70% of patients.   Patients who relapse twice require indefinite therapy with either prednisone or azathioprine. The dose is titrated as low as possible in order to prevent symptoms and to maintain AST below 5-fold normal. The median dose of prednisone required to achieve this is 7.5 mg/d. Recently, long-term therapy with azathioprine at a dose of 2 mg/kg/d was effective at maintaining remission in patients.

Treatment adverse effects   Cushingoid features, acne, and hirsutism develop in 80% of patients after 2 years of treatment, irrespective of the treatment regimen. Osteoporosis with vertebral compression, diabetes, cataracts, severe emotional lability, and hypertension may develop in patients who are treated with prolonged courses of high-dose prednisone. Premature treatment withdrawal is justified in patients who develop intolerable obesity, cosmetic changes, or osteoporosis.   Azathioprine can function as a steroid-sparing agent. The authors have had great success and minimal drug-related adverse effects using long-term therapy with prednisone 10 mg/d plus azathioprine 50 mg/d. Patients should be cotreated with calcium and vitamin D in order to prevent the development of steroid-induced osteoporosis. Regular exercise should be encouraged. Bone densitometry every 1-2 years should be used to monitor patients. Signs of early osteoporosis may warrant the institution of treatment with alendronate.   Azathioprine therapy can be complicated by cholestatic hepatotoxicity, nausea, vomiting, rash, cytopenia, and pancreatitis. These complications occur in fewer than 10% of patients treated with azathioprine at 50 mg/d.   Teratogenicity has been ascribed to treatment with azathioprine; however, the gastroenterology literature is replete with references that describe the safe use of azathioprine and 6-mercaptopurine in pregnant women with inflammatory bowel disease. Whether this observation can be extended to pregnant women with autoimmune hepatitis and whether azathioprine can be employed safely in these patients is unclear.   Hematologic malignancy has been reported in patients undergoing treatment with azathioprine; however, the risk of malignancy is thought to be low in patients with autoimmune hepatitis who are treated with low doses of the drug. The goals of pharmacotherapy are to reduce morbidity and prevent complications. Medications used include prednisone, prednisolone, and azathioprine.   Drug Category: Corticosteroids -- Drug Name   Prednisone (Deltasone, Orasone, Meticorten) -- Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. Adult Dose 5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve Pediatric Dose 4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk, as symptoms resolve Contraindications Documented hypersensitivity; viral, fungal or tubercular infections, peptic ulcer disease, osteoporosis Interactions Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin, may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteoporosis and osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use Drug Name   Azathioprine (Imuran) -- Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity. Adult Dose 1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d Pediatric Dose Initial dose: 2-5 mg/kg/d PO/IV Maintenance dose: 1-2 mg/kg/d PO/IV Contraindications Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT) Interactions Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine Pregnancy D - Unsafe in pregnancy Precautions Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated Drug Name   Prednisolone (Delta-Cortef, Econopred, Articulose-50) -- Decreases autoimmune reactions, possibly by suppressing key components of immune system. Adult Dose 5-60 mg/d PO/IV/IM in divided doses Pediatric Dose 0.1-2 mg/kg/d PO/IV/IM qd or divided tid/qid Contraindications Documented hypersensitivity; viral, fungal or tubercular infections, peptic ulcer disease, osteoporosis Interactions Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease the effect of corticosteroids Pregnancy C - Safety for use during pregnancy has not been established. Precautions Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis   Generic Name Brand Name(S) Azathioprine Imuran Corticosteroids - Chlorphenirahine Piriton Cyclosporin Neoral, Sandimmun, SangCya Diuretics - Mycophenolate CellCept Omeprazole Losec Phytomenadione (Vit K) Konakion Prednisolone Precortisyl Forte, Prednesol Ranitidine Zantac Spironolactone Aldactone Sucralfate Antepsin Tacrolimus Prograf Ursodeoxycholic Acid Destolit, Urdox, Ursofalk, Ursogal       Azathioprine Explanation: It is a powerful CYTOTOXIC and IMMUNOSUPPRESSANT drug. It is mainly used to reduce tissue rejection in transplant patients, but it can also be used to treat myasthenia gravis, rheumatoid arthritis, ulcerative colitis and several autoimmune diseases. Possible Side-Effects: Hypersensitivity reactions including dizziness, malaise, vomiting, fever, muscular pains and shivering, joint pain, jaundice, heart arrhythmias, low blood pressure (requiring withdrawal of treatment), symptoms of bone marrow suppression, which should be reported (eg bleeding or bruising), hair loss, increased susceptibility to infections, nausea, pneumonia and pancreatitis.   Corticosteroids Explantion: Steroid hormone secreted by the cortex (outer part) of the adrenal glands, or are synthetic substances that closely resemble the natural forms. There are two main types, glucocorticoids and mineralocorticoids. The latter assist in maintaining the salt-and water balance of the body. Corticosteroids such as the glucocorticoid HYDROCORTISONE and the mineralocorticoid FLUDROCORTISONE ACETATE can be given to patients for replacement therapy where there is a deficiency, or in Addison's disease, or following adrenalectomy or hypopituitarism. The glucocorticoids are potent ANTI-INFLAMMATORY and ANTI-ALLERGIC drugs and are frequently used to treat inflammatory and/or allergic reactions of the skin, airways and elsewhere. COMPOUND PREPARATIONS are available that contain both an ANTIBACTERIAL or ANTIFUNGAL drug with an anti-inflammatory corticosteroid and can be used in conditions where an infection is also present. However, these preparations must be used with caution because the corticosteroid component diminishes the patient's natural immune response to the infective agent. Absorption of a high dose of corticosteroid over a period of time may also cause undesirable, systemic side-effects. Possible Side-Effects: Mineralocorticoid adverse effects include hypertension, sodium and water retention and potassium loss. Glucocorticoid adverse effects include diabetes, osteoporosis, avascular necrosis, mental disturbances, euphoria, muscle wasting and possibly peptic ulceration. Corticosteroids may also cause Cushing's syndrome, suppressed growth in children and adrenal atrophy. If administered during pregnancy, they may affect adrenal gland development in the child. Suppression of the sympoms of infection may occuR.   Chlorphenirahine Explantion: Is an ANTIHISTAMINE drug. It is used to treat the symptoms of allergic conditions such as hay fever and urticaria (itchy skin rash) and is also occasionally used in emergencies to treat anaphylactic shock. Administration is either oral as tables or a syrup, or by injection. Side-effects: Because of its sedative side-effects, the performance of skilled tasks such as driving may be impaired. Injections may be irritant and cause short-lasting hypotension and stimulation of the central nervous system.   Cyclosporin Explantion: It is an IMMUNOSUPPRESSANT drug, which is particularly to limit tissue rejection during and following organ transplant surgery. It can also be used to treat severe, active rheumatoid arthritis and some skin conditions such as severe, resistant atopic dermatitis and) under special supervision) psoriasis. It has very little effect on the blood-cell producing capacity of the bone marrow, but does have liver toxicity. Possible Side-Effects: Include changes in blood enzymes, disturbances in liver, kidney and cardiovascular function, excessive hair growth, gastrointestinal disturbances, tremor, gum growth, oedema (accumulation of fluid in the tissues), fatigue and burning sensations in the hands and feet.   Duretics Explantion: Drugs used to reduce fluid in the body by increasing the excretion of water and mineral salts by the kidney, so increasing urine production.   Mycophenolate Explantion: see Cyclosporin Possible Side-Effects: Diarrhoea, vomiting, constipation, nausea, dyspepsia, abdominal pain, dizziness, insomnia, headache, tremor.   Omeprazole Explantion: Is an ulcer-healing drug. It works by being a proton-pump inhibitor and so interferes with the secretion of gastric acid from the parietal cells of the stomach lining. It is used for the treatment of benign gastric and duodenal ulcers. Possible Side-Effects: Diarrhoea or constipation, nausea, flatulence; dizziness, headaches, sleep disorders, disturbances of vision, hair loss, skin and mood disorders (some of these last side-effects occur only in the very ill).   Phytomenadione (Vit K) Explantion: Is a natural form of Vitamin K and is normally obtained from vegetables and dairy products. Phytomenadione can be used to treat Vit K deficiency, but not a deficiency caused by malabsorption states. Administration is either oral in the form of tables or by slow intravenous injection. Possible Side-effects: there may be liver damage if high doses are taken for a long period.   Prednisolone Explantion: It is a synthetic, glucocorticoid CORTICOSTEROID with ANTI-INFLAMMATORY properties. It is used in the treatment of a number of rheumatic and allergic conditions (particularly those affecting the joints or lungs) and collagen disorders. It is also an effective treatment for ulcerative colitis, inflammatory bowel disease, Crohn's disease, rectal or anal inflammation, haemorrhoids and as an IMMUNOSUPPRESSANT in the treatment of myasthenia gravis. It may also be used for systemic corticosteroid therapy. Possible Side-Effects: See Corticosteroids     Ranitidine Explantion: Is an effective and extensively prescribed H2-antagonist and ulcer-healing drug. It is used to assist in the treatment of benign peptic (gastric and duodenal) ulcers, to relieve heartburn in cases of reflux oesophagitis (caused by regurgitation of acid and enzymes into the oesophagus). Possible Side-Effects: Tiredness, rash, dizziness, headache or confusion.   Spironolactone Explantion: Is a diuretic drug of the aldosterone-antagonist type. It is also potassium-sparing and so can be used in conjunction with other types of diuretic, such as the thiazides, which cause loss of potassium, to obtain a more beneficisal action. It can be used to treat oedema (accumulation of fluid in the tissues) associated with aldosteronism (abnormal production of aldosterone by the adrenal gland), in congestive heart failure treatment, kidney disease and fluid retention and ascites caused by liver disease. Possible Side-Effects: Gastrointestinal disturbances, impotence and gynaecomastia (enlargements of breats) in men; irregular periods in women; skin rashes, raised blood potassium and lowered blood sodium levels.   Sucralfate Explantion: Is a drug that is a complex of aluminium hydroxide and sulphated sucrose. It can be used as a long-term treatment of gastric and duodenal ulcers. It has very little antacid action, but is thought to work as a cytoprotectant by forming a barrier over an ulcer, so protecting it from acid and the enzyme pepsin and allowing it to heal. Possible Side-Effects: Constipation, diarrhoea, nausea, indigestion, gastric discomfort, dry mouth, skin rash and itching.   Tacrolimus Explantion: It is a IMMUNOSUPPRESSANT drug (a MACROLIDE ANTIBIOTIC) that is used particularly to limit tissue rejection during and following organ transplant surgery (particularly of liver or kidney). Possible Side-Effects: See Cyclosporin   Ursodeoxycholic Acid Explantion: A drug that can dissolve some gallstones in situ. Administration is oral in the form of capsules or tablets. Possible Side-Effects: Diarrhoea and itching, mid liver dysfunction and changes in blood enzymes.

Surgical Care:

• Liver transplantation

• This procedure is an effective form of therapy for patients with decompensated cirrhosis caused by autoimmune hepatitis. This procedure also may be used to rescue patients who present with fulminant hepatic failure secondary to autoimmune hepatitis.

• The long-term outlook after liver transplantation is excellent, with 5-year survival rates reported at 90% or more. Positive autoantibodies and hypergammaglobulinemia tend to disappear within 2 years of transplantation.

• Recurrence of autoimmune hepatitis is uncommon after liver transplantation. It has been reported primarily in inadequately immunosuppressed patients and HLA DR3-positive recipients of HLA DR3-negative donors.

Diet:

• Patients with acute autoimmune hepatitis and symptoms of nausea and vomiting may require intravenous fluids and even total parenteral nutrition; however, most patients can tolerate a regular diet. A high caloric intake is desirable.

• Patients with cirrhosis secondary to autoimmune hepatitis may develop ascites. A low salt diet (generally <2000 mg of sodium per d) is mandatory in these individuals. Patients should continue to consume protein (ie, >1.1 g protein/kg body weight), given the catabolic nature of the disease and patients' high risk for developing muscle wasting.

Activity: Most patients do not need hospitalization, although this may be required for clinically severe illness. Forced and prolonged bed rest is unnecessary, but patients may feel better with restricted physical