Multidimensional indications and prognostic assessment for liver transplantation: covering viral cirrhosis, metabolic disorders, and surgical guidelines for tumors.

(II) Indications for Liver Transplantation 1. Cirrhosis (1) Viral Cirrhosis. Chronic hepatitis B, chronic hepatitis C, and chronic hepatitis D can all cause cirrhosis. 50% of chronic hepatitis B patients with persistently positive HBsAg/HBeAg may develop cirrhosis, while patients with positive HBsAg/HBeAb or HBsAb/HBeAb generally do not develop cirrhosis. Hepatitis D virus relies on hepatitis B virus for replication and expression, therefore its infection only occurs in hepatitis B patients. Hepatitis C has a 50% chance of developing into chronic active hepatitis, and 10% to 30% of these patients develop cirrhosis within 3 to 6 years. Hepatitis B virus damages hepatocytes by inducing the body's autoimmunity, while chronic hepatitis D and chronic hepatitis C are caused by viral damage to primary hepatocytes. For hepatitis C patients, the 10-year survival rate after liver transplantation can reach 62%. After liver transplantation, hepatitis C can relapse, with a relapse rate of about 17%. Among them, 12% to 16% of patients are only hepatitis C virus carriers without any clinical symptoms or abnormal laboratory tests, 60% to 70% of patients have only mild abnormal laboratory tests without any clinical symptoms, and 24% to 27% of patients may develop clinical symptoms of various degrees. However, only 8% to 10% of patients will develop cirrhosis within 10 years and need a second liver transplant. Hepatitis C with HCV1b virus has the highest relapse rate, but the 5-year survival rate is not significantly different from that of the uninfected group. (2) Alcoholic cirrhosis. Fibrosis in alcoholic cirrhosis first occurs in the terminal branches of the hepatic venules, i.e., around the central vein, caused by the damage to the liver caused by acetaldehyde, a derivative of ethanol. Fibrosis around the central vein obstructs the patency of the pores of the hepatic sinusoidal endothelial cells, affecting the exchange of nutrients and metabolic products between hepatocytes and blood. When the lesion is severe, cirrhosis can occur. (3) Primary cholestatic cirrhosis. Primary cholestatic cirrhosis (PBC) is a disease characterized by non-suppurative cholangitis as an early lesion, progressive jaundice as the main manifestation, and death from liver failure. It affects 90% of cases in women, especially middle-aged women. This disease occurs worldwide, with a higher incidence in Europe than in Asia, and is relatively rare in my country. The most common complications of PBC are esophageal variceal bleeding and osteoporosis. When serum total bilirubin exceeds 180 mmol/L, it indicates the end stage of the disease, and most patients will die within 2 years. Therefore, liver transplantation should be considered when esophageal variceal bleeding, severe osteoporosis, and bilirubin levels exceeding 180 mmol/L occur. Postoperative outcomes are good, with a 5-year survival rate of up to 95%. Except for osteoporosis, other pre-existing complications can be corrected after surgery. The most common postoperative complications are bone pain and fractures; therefore, some advocate for liver transplantation before these complications occur. Relapse of PBC after liver transplantation has also been observed. 2. Wilson's disease, also known as hepatolenticular degeneration, is a metabolic disorder primarily affecting adolescents. It is characterized by cirrhosis, softening and degeneration of the basal ganglia of the brain, and corneal pigment rings (Kayser-Fleischer rings, KF rings). Corneal KF rings and decreased serum ceruloplasmin are important diagnostic criteria. The vast majority of cases develop between the ages of 5 and 25, with some cases appearing as late as age 50. Initial symptoms in 42% of cases are related to liver disease, manifesting as acute severe hepatitis, chronic active hepatitis, and cirrhosis; 44% present with neuropsychiatric symptoms such as stuttering, gait stiffness, difficulty writing, and drooling; and approximately 12% present with endocrine or hematologic symptoms secondary to liver disease, such as amenorrhea in young women and delayed puberty and gynecomastia in boys. Liver transplantation is recommended for patients with the following conditions: ① decompensated cirrhosis; ② intolerance to drug therapy or ineffective drug therapy after 3 months; ③ fulminant hepatic failure. 3. Liver Tumors: In the early stages of liver transplantation, hepatocellular carcinoma (HCC) was the primary indication, often chosen from patients with advanced, inoperable HCC. Although early post-transplant outcomes for HCC patients were good, due to post-operative immunosuppression, 60% of patients experienced tumor recurrence within six months. Data from seven European liver transplant centers showed a 2-year survival rate of only 9%–18% for HCC patients after transplantation. This data indicates a significant correlation between tumor size and survival rate after liver transplantation. For tumors smaller than 5 cm in diameter, the 1-, 3-, and 5-year survival rates were 77%, 68%, and 68%, respectively, while for tumors larger than 5 cm, the rates were 51%, 25%, and 25%. Some patients undergoing liver transplantation for benign end-stage liver disease were found to have small HCCs ("accidental cancers") during surgery; some reports indicate a 2-year survival rate of up to 88% for these patients. Currently, patients with tumors smaller than 5 cm in diameter and severe cirrhosis are generally considered surgical candidates. Hepatic fibrolamellar carcinoma, due to its slower development, is suitable for liver transplantation, with a 2-5 year survival rate higher than that of hepatocellular carcinoma. However, the long-term survival rate is not significantly different from that of hepatocellular carcinoma. The 1-year survival rate after liver transplantation for cholangiocarcinoma is only about 36%, which is not significantly different from the survival rate of patients without specific treatment. Therefore, most liver transplant centers consider it a contraindication for liver transplantation. Metastatic liver cancer, due to its high recurrence rate after surgery, should also be considered a contraindication for liver transplantation. 4. Fulminant Hepatic Failure: Fulminant hepatic failure (FHF) refers to a syndrome characterized by the sudden occurrence of massive hepatocellular necrosis or severe liver function impairment in patients without prior liver disease, leading to hepatic coma within 8 weeks of onset. Acute hepatic failure due to acute exacerbations of chronic liver disease is not included in this category. In my country, 85.5%–90% of fulminant hepatic failure cases are caused by acute severe hepatitis, a situation similar in Europe and America. Drug poisoning and Reye's syndrome can also cause fulminant hepatic failure. In some regions of Germany, consuming poisonous mushrooms is also a contributing factor. The cause of some cases of fulminant hepatic failure remains unknown. The mortality rate of fulminant hepatic failure is very high, exceeding 80%. Liver transplantation can significantly improve the survival rate of these patients; in other words, liver transplantation is currently the only effective means of saving these patients. Because liver transplantation surgery for these patients is often performed in emergency situations, their conditions are critical, and sometimes ABO-incompatible donor livers are necessary, resulting in a lower survival rate than other patients. However, there are reports of a one-year survival rate of up to 80%. In recent years, adjuvant liver transplantation has also shown promising prospects for treating this disease.