Introduction
From UC San Diego Several scholars in the journal summarized the impact of liver fibrosis on patient morbidity and mortality, as well as current and future treatments for liver fibrosis.
Hepatitis B, Hepatitis C, and fatty liver disease (continuous liver cell damage) can lead to liver fibrosis. Irrespective of the etiology of liver disease, liver-related mortality increased exponentially with fibrosis stage. Progress to cirrhosis is associated with higher rates of mortality and hepatocellular carcinoma (HCC).
Liver fibrosis also affects outcomes after liver transplantation in adults and children , requiring the patient to retransplant. Currently antiviral therapy can reverse liver fibrosis in patients with hepatitis B and C, but there is no direct treatment for liver fibrosis. Studies have shown that the use of novel drug targets can successfully reverse liver fibrosis in a mouse model of chronic liver disease. Current therapies focus on preventing myofibroblast activation. Further research in these areas could lead to the development of drugs to treat liver fibrosis, which could have a major impact on patient survival.
Staging and classification of liver fibrosis
Liver fibrosis has a variety of staging scoring systems (Table 1). The Knodell scoring system was proposed in 1981 to divide liver fibrosis into three stages. Liver fibrosis was classified into stages 0-4 by the Batts-Ludwig and Scheuer scoring system. The Ishak scoring system classifies liver fibrosis into stages 0-6.
Table 1 Basic stages and classifications of liver fibrosis
Clinical significance of liver fibrosis staging
hepatic fibrosis and mortality< /strong>
Epidemiological studies have shown that staging of liver fibrosis has significant clinical significance. Increased fibrosis stage was associated with increased all-cause mortality compared with patients without fibrosis or stage 1 fibrosis. Mortality from liver fibrosis may vary by etiology, but liver-related mortality increases exponentially with fibrosis stage regardless of the etiology of liver disease. Severe fibrosis has a significant impact on 10-year mortality before alcoholic liver disease (ALD) progresses to cirrhosis. In nonalcoholic fatty liver disease (NAFLD), higher stage fibrosis is the most important predictor of mortality. In a NAFLD study, the 10-year transplant-free survival rate for patients with stage 4 fibrosis and Child-Pugh class (CP) A6 was only 17%. In contrast, patients with stage 4 fibrosis on CP-A5 had a 10-year transplant-free survival rate of 74% and 94% with stage 3 fibrosis.
Liver fibrosis progresses to cirrhosis
Liver-related mortality increases as fibrosis progresses to cirrhosis . An Italian study evaluating the effect of the degree of decompensation of cirrhosis on mortality over 3 years in 494 patients showed that with increasing events of decompensation, mortality also increased. The 5-year mortality rate for patients with compensated cirrhosis was 1.5%, compared with 88% for patients with 2 events of decompensation, regardless of Child Pugh score or Model for End-Stage Liver Disease score. An analysis of the natural history of cirrhosis in 1317 patients in Sweden over a 10-year period showed a 10-year decompensation rate of 89%, of which 75% died during the study period, the most common cause of death being liver failure and complications of cirrhosis.
The decompensation rate of different diseases may vary. The 10-year decompensation rate of alcoholic cirrhosis is 89%. Hepatitis was 58% and cryptogenic cirrhosis was 75%. Follow-up of patients from 4 countries showed that hepatitis C virus (HCV) cirrhosis had a higher incidence of liver-related complications, including HCC, than NAFLD cirrhosis. Patients with cirrhosis, especially decompensated cirrhosis, have higher readmission rates and higher medical costs.
Liver Fibrosis and HCC strong>
Liver fibrosis and cirrhosis are also associated with the occurrence of HCC. HCC is a common cause of death in patients with cirrhosis and the leading cause of liver-related death in patients with compensated cirrhosis. In the aforementioned Swedish cohort, 15% of patients with cirrhosis died from HCC over 10 years. Although cirrhotic patients were more likely to develop HCC than non-cirrhotic or stage 1/2 fibrosis patients, the incidence of HCC increased with increasing fibrosis stage. The incidence of HCC varies among studies. A study of 634 Swedish patients with autoimmune hepatitis (AIH) showed that 4% of patients with cirrhosis developed HCC, and the incidence was 0.3%. Another study including Danish AIH patients showed a 10-year cumulative risk of HCC of 0.7%.
The incidence of HCC varies among different diseases. Diseases with the highest incidence of HCC include hereditary hemochromatosis (5-year risk of 21%), hepatitis B infection (5-year risk of 10% to 15%), and HCV cirrhosis (5-year risk of up to 17% in Western countries). %, even as high as 30% in Japan). To evaluate the impact of HCV treatment with novel direct-acting antiviral drugs on the incidence of HCC, the results showed that patients with cirrhosis and treatment failure had a higher incidence of HCC compared with patients without cirrhosis and achieving a sustained virological response (SVR). Other studies have also shown that the incidence of HCC is significantly reduced in patients with fibrosis and cirrhosis who achieve SVR.
Liver Fibrosis and Liver Transplantation< /strong>
In adult patients, the development of liver fibrosis after liver transplantation has been shown to be a chronic allograft Important indicator of exhaustion. The most common causes of late graft failure after transplantation are the recurrence of the primary disease, the development of new-onset disease (AIH or NAFLD), and chronic rejection, which can lead to liver fibrosis and cirrhosis. Liver fibrosis progresses faster in patients with HCV recurrence after transplantation than before transplantation. Post-transplant nonalcoholic steatohepatitis (NASH) recurrence rates were also higher, but liver fibrosis rates were lower, with bridging fibrosis or cirrhosis occurring in 5% and 10% of patients 5 and 10 years after transplantation, respectively.
There has also been an increase in children with liver disease in recent years, mainly because of the higher incidence of NAFLD, which is associated with childhood metabolic syndrome and obesity. increase about. Compared with peers, children with metabolic syndrome and obesity have a higher mortality rate from NAFLD and may lead to transplantation at a young age. Biliary atresia is the most common indication for liver transplantation in children. Some children with chronic hepatitis develop liver fibrosis within a few years after liver transplantation, and some develop liver cirrhosis later.
Treatment of liver fibrosis
There is no direct treatment for liver fibrosis, and further research is needed. Removal of potential pathogens of liver disease may prevent or improve liver fibrosis. Bloodletting (phlebotomy) and iron chelators for hereditary hemochromatosis improve liver fibrosis. There are specific treatments for specific liver diseases, such as direct-acting antiviral drug therapy, which can reduce the incidence of HCV progression to cirrhosis and HCC. Specific drug for chronic hepatitis B can reverse liver fibrosis and cirrhosis. Cessation of alcohol intake in patients with ALD improves prognosis and prevents progression to cirrhosis. Weight loss through bariatric surgery or diet has been shown to improve inflammation and fibrosis in NASH.
Studies have shown that the use of novel drug targets can successfully reverse liver fibrosis in a mouse model of chronic liver disease. Current therapies focus on preventing Myofibroblast activation. Further research in these areas may lead to the development of drugs to treat liver fibrosis, which will have a major impact on patient survival.