Liver amyloidosis

　　The etiology and pathogenesis of amyloidosis are not yet clear. It is generally believed that it is mainly caused by the infiltration of amyloidogenic substances between cells due to various reasons, or their deposition under the basement membrane of small blood vessels, or along the reticular fiber scaffold. As the lesion progresses, these deposited substances compress and destroy these tissues, leading to organ failure and death. The amino acid sequence analysis of amyloid fibers isolated and purified from amyloidosis fibers shows that there are 3 types of protein:

　　1. AL type protein

　　Derived from the light chain of immunoglobulins (especially the variable region), the N-terminal sequence and a part of the immunoglobulin light chain are homologous, including type and type. Type light chain is more likely to form amyloid fibrils than type, and is seen in primary amyloidosis and amyloid deposition associated with multiple myeloma.

　　2. AA type protein

　　It has the same N-terminal sequence as the non-immunoglobulin protein called AA protein. The amyloid fibrils seem to be unrelated to the light chain, and the main amyloid fibrils are composed of a protein different from immunoglobulin, which may be due to the proteolytic transformation of immunoglobulins produced by plasma cells by lysosomal enzymes of phagocytes. It is seen in secondary and familial Mediterranean fever associated with amyloid deposition.

　　3. AF type protein

　　Amyloid fibrils are mainly normal or abnormal prealbumin complexes (molecular weight 14,000), usually single amino acid substitution products of thyroid-stimulating hormone protein (prealbumin), followed by 2-microglobulin, mainly seen in familial amyloidosis.

　　Liver amyloidosis may complicate secondary infections, renal and cardiac failure, and liver cirrhosis with ascites. Liver cirrhosis with ascites refers to clinical symptoms caused by repeated inflammation, fibrosis, and liver cirrhosis due to various pathological factors such as portal hypertension, hypoalbuminemia, and water and sodium retention after liver disease. Liver cirrhosis with ascites is not a single disease but a common clinical manifestation of the terminal stage (decompensation stage) of many liver diseases. Common diseases causing liver cirrhosis with ascites include hepatitis B, hepatitis C, alcoholic hepatitis, and autoimmune hepatitis. Once liver disease progresses to the stage of liver cirrhosis with ascites, it often indicates that liver cirrhosis has reached the decompensation stage. Without active intervention and treatment, the prognosis is poor.

　　Liver amyloidosis has no specific symptoms and signs in clinical practice. Its symptoms depend on the primary disease, the location, amount of amyloid deposition, and the organs and systems involved. Symptoms are often masked by the primary disease.

　　More than 95% of secondary systemic amyloidosis involves the liver, commonly presenting as liver enlargement, upper abdominal distension, and anorexia. A few cases may present with severe liver enlargement (liver weight can reach more than 7kg), but the liver function damage is relatively mild. Occasionally, portal hypertension may lead to esophageal varices, gastric fundus varices, and ascites, and a very few cases may have jaundice.

　　To prevent liver amyloidosis, it is necessary to actively treat the primary disease and pay attention to physical exercise in daily life. If the existing disease is severe, close observation of the condition is required.

　　1. Actively treat the primary disease: For patients with secondary amyloidosis, if the primary diseases such as rheumatoid arthritis, chronic osteomyelitis, tuberculosis, and multiple myeloma can be controlled, liver amyloidosis may regress.

　　2. Active physical exercise: Enhancing the body's immune function is helpful in preventing the occurrence of the disease. In addition, patients should be advised to adjust their emotions and maintain a pleasant mood.

　　3. The cause of death in patients with liver amyloidosis is secondary infection and renal and cardiac dysfunction. Therefore, it is necessary to closely observe the changes in the condition, and if the above conditions occur, immediate rescue should be carried out to reduce the mortality rate.

　　The liver function (alanine aminotransferase, aspartate aminotransferase) and coagulation time of patients with liver amyloidosis are mostly normal or slightly abnormal, mostly showing elevated gamma-glutamyl transpeptidase and alkaline phosphatase. Bilirubin exceeding 85.5μmol/L is rare, and anemia, proteinuria, and other symptoms may occur. Erythrocyte sedimentation rate can be normal or accelerated. Imaging examinations lack specificity, and ultrasound examinations mainly show increased liver volume, coarse granular uniform echo of liver parenchyma, possible dilatation of the portal vein, and sometimes the formation of ascites. CT mainly shows liver enlargement, diffuse hypodense areas in the liver, no obvious enhancement, and no displacement of intrahepatic blood vessels.

　　Patients with liver amyloidosis should ensure a low-salt diet, limit the intake of sodium salts, pay attention to the balance of sodium and potassium, which is conducive to preventing the occurrence of arrhythmias and heart failure. Avoid cold, hot, and spicy foods, do not drink strong tea or coffee, avoid smoking and drinking. Adopt a low-calorie diet to reduce the workload of the heart. Eat more fresh vegetables and fruits, balance the diet, supplement adequate high-quality protein, and ensure the supply of myocardial nutrition. Pay attention to rest more in daily life, avoid staying up late, and avoid fatigue. Specific dietary requirements should be formulated according to different symptoms, and it is necessary to consult a doctor specifically for different dietary standards.

　　There is currently no specific therapy for liver amyloidosis. The aim of treatment is to prevent the further deposition of amyloid substances and promote or accelerate the absorption of already deposited amyloid substances.

　　1. Treatment for primary amyloidosis

　　The common treatment plan is the Melphalan (phenylalanine mustard) Prednisone (MP) regimen. Since alkylating agents are ineffective against non-immunoglobulin amyloidosis, it is necessary to confirm the diagnosis of primary amyloidosis before starting treatment. Some people have compared the treatment results of the MP regimen with colchicine, and long-term treatment with the MP regimen can completely regress liver amyloidosis, restore the normal size of the enlarged liver, soften the texture, significantly reduce the elevated serum alkaline phosphatase levels, and prolong the survival period compared to colchicine. The usage of the MP regimen: Melphalan 0.15mg/(kg·d), taken orally in two doses; Prednisone 0.8mg/(kg·d), taken orally in four doses, with a week as one course, and repeated every 6 weeks, which can last for several months to several years; the dose of Melphalan is increased by 2mg/d per course until moderate leukopenia or thrombocytopenia occurs, and if severe leukopenia or thrombocytopenia occurs, the dose of Melphalan should also be reduced accordingly. It is noteworthy that serious viral infections can occur during the treatment with the MP regimen.

　　2. Treatment of secondary amyloidosis

　　(1) Control of underlying diseases: such as chronic osteomyelitis, tuberculosis, rheumatoid arthritis, and others. Good control of the basic etiology can stop the development of amyloidosis even regression.

　　(2) Dimethyl sulfoxide (DMSO): Originally an industrial solvent, it was later found to have the following effects:

　　① In vitro, it can dissolve amyloid fibers and increase their sensitivity to degrading enzymes.

　　② Inhibit the synthesis of serum amyloid A and reduce the deposition of AA protein in tissues.

　　③ Inhibit inflammatory reactions.

　　Dimethyl sulfoxide (DMSO) is ineffective for primary amyloidosis, but it can improve renal function, restore the enlarged liver to normal, slightly reduce amyloid substances, and improve survival time in patients with secondary amyloidosis. Its usage is to prepare a 10% solution with 15g and take it three times with juice before meals, at least for 6 months. If it is ineffective, other methods should be used; for those who respond, continue to use it, gradually reduce the dose after the condition is controlled, and maintain it at an appropriate dose, with the course of treatment lasting for several years. Early and rapid dose reduction or abrupt discontinuation of medication can lead to deterioration of the condition. Dimethyl sulfoxide is non-toxic and safe for long-term use. The only adverse reaction is mild nausea, but the odor of exhaled breath is unpleasant, and many patients therefore discontinue treatment.

　　(3) Symptomatic treatment: Effective treatment of heart failure and renal failure, careful use of digitalis, and consideration of renal transplantation may be possible.