What are the methods to treat liver disease?

Immune liver disease is also a type of liver disease, but it is a more special chronic liver disease. There are many causes of this disease, such as environmental reasons, or it may be a mutagenesis caused by biochemical factors. So how do we treat this disease? First we need to understand the condition, and then use medication safely according to the condition. Here are some methods to treat liver disease.

1. Causes

The occurrence of AIH requires antigen activation. The pathogenesis of AIH induced by environmental factors has not yet been elucidated. Viruses (such as HBV, HCV, Epstein-Barr virus, measles virus, etc.) play a more positive role in stimulating immune responses. Viral antigen epitopes and certain liver antigens have the same determinants, which induce cross-reactions through "molecular mimicry" and lead to autoimmune liver disease. A variety of nonspecific autoantibodies can be detected in the serum of some patients infected with HCV. It is speculated that this is probably due to the fact that HCV infection changes the protein components on the liver cell membrane. Biological, physical or chemical factors can also stimulate changes in autoantigens. Drugs such as methyldopa, nitrofurantoin, diclofenac, minocycline, and interferon can cause liver damage similar to AIH.

2. Diagnosis and Differentiation

1. Primary biliary cirrhosis

It is similar to AIH in clinical symptoms and laboratory tests, but is more common in middle-aged women, with fatigue, jaundice, and skin itching as the main manifestations. Liver function tests show significantly increased alkaline phosphatase and γ-glutamyl transpeptidase, increased serum total cholesterol, triglycerides, and low-density lipoprotein, and increased immunoglobulins, with IgM being the most prominent. Serum anti-mitochondrial antibody M2 is a disease-specific antibody. The pathological presence of bile duct epithelial damage and inflammation, bile duct disappearance, and portal granulomas are helpful in the diagnosis of the disease.

2. Primary sclerosing cholangitis

It is characterized by extensive inflammation and fibrosis of the intrahepatic and extrahepatic biliary systems. It is more common in young and middle-aged men and is often accompanied by ulcerative colitis. 84% of patients are ANCA-positive, but it is not specific. Cholangiography can show alternating stenosis and dilatation of the intrahepatic and extrahepatic bile ducts, presenting a beaded-like change. Diagnosis requires exclusion of secondary causes such as tumors, stones, surgery, and trauma. When the lesion only involves the small intrahepatic bile ducts, diagnosis requires histological examination, and the typical change is fibrous cholangitis.

3. Acute and chronic viral hepatitis

Hyperglobulinemia and circulating autoantibodies may also occur, but the antibody titer is low and the duration is short-lived. Testing of serum viral antigens and antibodies is very helpful for identification.

4. Alcoholic fatty hepatitis

Patients with a history of drinking alcohol are often characterized by elevated serum IgA levels. Although ANA and SMA may be positive, the titers are generally low, and anti-LKM1 and PANCA positivity are rarely seen.

3. Treatment Methods

1. Endpoints and strategies for initial treatment

Adult AIH should be treated continuously until remission, treatment failure, incomplete response, or drug toxicity occurs (see Table 3). In 90% of patients, serum transaminase, bilirubin and γ-globulin levels improve within 2 weeks of starting treatment, but histological improvement lags behind by 3 to 6 months, so it usually takes more than 12 months of treatment to achieve complete remission. Although some patients continue to remit after stopping treatment, most patients require maintenance treatment to prevent relapse.

2. Relapse and its countermeasures

Relapse refers to a re-increase of transaminases exceeding 3 times the upper limit of normal and/or a serum γ-globulin level exceeding 2,000 mg/dL after remission and drug discontinuation. It usually occurs within 2 years after stopping the drug. Patients with relapse are at increased risk of progression to cirrhosis, gastrointestinal bleeding, and death from liver failure. For patients with first relapse, the initial treatment plan can be re-selected, but for patients with at least 2 relapses, the treatment plan needs to be adjusted. The principle is to use lower doses and longer maintenance treatment to relieve symptoms and keep the transaminase level below 5 times the normal value. Generally, after inducing remission with prednisone, the dose is reduced by 2.5 mg per month until the lowest dose that maintains the above indicators is achieved (the lowest average dose for most patients is 7.5 mg/d), and then long-term maintenance treatment is carried out. To avoid the adverse reactions of long-term use of glucocorticoids, after the condition improves, the dose of prednisone can be reduced by 2.5 mg per month while azathioprine can be increased by 2 mg/kg per day until prednisone is withdrawn and the minimum maintenance dose of azathioprine is reached. Alternatively, the lowest dose of the combination therapy may be used.

3. Alternative treatment

Patients who still have no histological remission after high-dose glucocorticoid treatment or who cannot tolerate drug-related adverse reactions may consider using other drugs as alternatives. For example, cyclosporine A, tacrolimus, budesonide, etc. may be effective for adult patients with glucocorticoid resistance. For those who cannot tolerate azathioprine, 6-mercaptopurine or mycophenolate mofetil can be tried. In addition, ursodeoxycholic acid, methotrexate, cyclophosphamide, etc. can also be tried, but the efficacy of the above drugs still needs to be confirmed by large-scale clinical trials.