Amyloidosis is a disease caused by the deposition of extracellular amyloid material in the walls and tissues of blood vessels. The disease mainly affects the heart, kidney, liver, spleen, gastrointestinal tissues and organs such as muscles and skin. When the liver is involved, it is called hepatic amyloidosis. A. Classification of amyloidosis There is no comprehensive and satisfactory classification of peripheral amyloidosis, among which the classification according to the pathogenesis is the most adopted and is divided into five categories, namely: (1) primary amyloidosis; (2) amyloidosis associated with multiple myeloma; (3) secondary amyloidosis; (4) focal amyloidosis; (5) familial amyloidosis. Hepatic amyloidosis is precisely a part of circumferential amyloidosis, which is roughly divided into the following three types according to what is seen under the microscope: 1. Intrahepatic lobular infiltrate type The amyloid containing immunoglobulin light chain fragments (AL) is deposited in the Diss space and sinusoidal space, and the normal hepatocyte cords are extruded or distorted, leaving only a small amount of normal hepatocytes. This type accounts for about 25% of hepatic amyloidosis. 2.Confluent area and perivascular infiltration type Amyloid (AA) infiltrates the vascular wall in the confluent area, also called vascular type, and the liver parenchyma may not be invaded, or only a small amount of amyloid infiltrates into the Diss space and sinusoidal space. It accounts for about 40% or more of hepatic amyloidosis. 3.Mixed type has both of the above two types of changes, accounting for about 20%. Clinical manifestations Focal hepatic amyloid infiltration may not show symptoms, but only detected by ultrasound, CT or biopsy. Peripheral amyloidosis involving the liver is reported in 17% to 90% of cases. At least 50% exhibit hepatomegaly and splenomegaly in about 8%, with minimal jaundice at the beginning of the disease. Severe portal hypertension, ascites, and variceal hemorrhage may occur. Hypoproteinemia and hypercholesterolemia may be present in cases of simultaneous hepatic and renal involvement. Hepatic amyloidosis is part of the peripheral amyloidosis, so systemic manifestations and other systemic manifestations are common. Common first symptoms include fatigue, weakness, weight loss, shortness of breath after exertion, and edema. Depending on the organ involved, corresponding symptoms may appear, such as carpal tunnel syndrome, nephrotic syndrome, congestive heart failure, malabsorption syndrome, peripheral neuropathy or postural hypotension. Waxy skin disease and megalingualism are very valuable diagnostic signs. Laboratory diagnosis General laboratory tests ALP is elevated, mostly within 2 times the upper limit of normal, there may be mild jaundice, transaminases are mostly normal. Amyloidosis often has coagulation disorders, mainly prolonged prothrombin time. Radionuclide sulfur colloidal technetium liver scan shows uniform and consistent mild reduction of radioactive uptake in the liver, which is an auxiliary diagnostic value for hepatic amyloidosis and can dynamically observe the progress of the disease and treatment effect. Ultrasound imaging shows irregular dense echogenic clusters in the liver, but is not specific, while CT imaging shows hypodensity in the liver. Biopsy is the primary and most reliable means of diagnosing systemic amyloidosis. Biopsy of subcutaneous fatty tissue in the abdomen has the highest positive rate, up to 95% in AL and 66% in AA, and is safe and easy to perform, while rectal biopsy is 85% positive and gingival biopsy is about 50% positive. The liver is invaded in 50% of patients with systemic amyloidosis, but the resulting clinical liver disease is uncommon. Moreover, liver puncture biopsy can cause serious, even fatal, bleeding complications. Therefore, liver biopsy is rarely necessary to confirm amyloid infiltration of the liver in patients with established systemic amyloidosis. Biopsies can be performed under direct laparoscopic view when necessary. Confirmation of the diagnosis of hepatic amyloidosis requires a liver puncture biopsy. The amyloid material in the tissue is stained with Congo red and shows a green bifollicular light under polarized microscopy, which is of diagnostic value. With the help of immunohistochemical methods, the application of specific antisera can precisely distinguish amyloid and different light chain types, which is important not only for diagnosis but also for the selection of treatment options. The aim of treatment of amyloidosis is to prevent further deposition of amyloid material and to promote or accelerate the absorption of the deposited amyloid material. For patients with secondary amyloidosis, if the underlying causes (chronic osteomyelitis, tuberculosis, rheumatoid arthritis, etc.) are controlled, amyloidosis can stop developing or even subside. Patients with primary amyloidosis currently use the following therapeutic measures: 1. The usage of MP program with the combination of phenylalanine nitrogen mustard (melphalan) and prednisone (prednisone): phenylalanine nitrogen mustard 0.5mg/(kg/d) in two doses, prednisone 0.8mg/kg.d) in four doses, 7d as a course of treatment. The course of treatment is repeated every 6 weeks for months to years. Phenylalanine nitrogen mustard is increased by 2 mg/d per course until moderate leukocytopenia or thrombocytopenia occurs. If severe leukocytopenia or thrombocytopenia occurs, the dose of phenylalanine mustard should be reduced accordingly. 2, dimethyl sulfoxide (DMSO) was originally an industrial solvent, in 1974 Isobe and Osserman first found that it can dissolve amyloid fibrils in vitro, in addition to inhibit serum amyloid (SAA) synthesis, inhibit the inflammatory response. DMSO is used as a 10% solution per 15g, divided into 3 doses with juice before meals; apply for at least 6 months after starting treatment, and try other methods if not effective. If it is effective, continue to use it and gradually reduce the dose after the disease is controlled and maintain it at the appropriate dose; the course of treatment can be up to several years. DMSO is non-toxic and safe for long-term use, but patients have a bad odor when breathing. The effect is unsatisfactory. 3.Colchicine Colchicine can inhibit the synthesis of SAA in hepatocytes and prevent casein-induced AA amyloidosis, which is clinically used to treat familial Mediterranean fever with amyloidosis with good effect. early application can still prevent or delay the occurrence of renal failure; significantly prolong the survival. The efficacy of colchicine on other types of amyloidosis has yet to be studied. V. Prognosis The prognosis of patients with amyloidosis depends on the etiology and the degree of kidney invasion. The median survival is about 1 year, with a 5-year survival rate of about 13% and a 10-year survival rate of only 1%. Patients with elevated serum bilirubin (>25umol/L) have a poor prognosis and all die within 5 months. The common causes of death are secondary infections and cardiac and renal failure.