Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05986383 |
| Other study ID # |
21408-0-03 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 2023 |
| Est. completion date |
March 2024 |
Study information
| Verified date |
August 2023 |
| Source |
Beijing Tsinghua Chang Gung Hospital |
| Contact |
Jiahong Dong, academician |
| Phone |
18810108028 |
| Email |
dongjiahong[@]mail.tsinghua.edu.cn |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Liver failure (PHLF) after hepatectomy is a relatively serious postoperative complication.
Previous studies have shown that liver reserve function is related to PHLF. The "Chinese
expert consensus decision tree for hepatectomy" implemented recommends different surgical
methods according to the liver function of patients and the standardized residual functional
liver volume ratio, so as to achieve accurate hepatectomy and prolong the survival of
patients. In the retrospective study, it showed the safety and effectiveness of the decision
tree under the condition of extended hepatectomy indications, but it lacked prospective
research to evaluate. Therefore, this study intends to evaluate the safety and effectiveness
of hepatectomy under the guidance of Chinese expert consensus decision tree through
prospective research.
Description:
Hepatectomy is an effective treatment for primary liver cancer, with excellent efficacy and
controllable safety . The incidence of non fatal complications after Hepatectomy is as high
as 45%, ranging from less serious events to life-threatening complications, including
infection or sepsis, bleeding, leakage or cardiopulmonary events. Liver Function
Insufficiency is a serious complication, which is also described as Post hepatectomy Liver
failure (PHLF) after Hepatectomy. PHLF has many definitions. Balzan and his colleagues put
forward the "50-50 standard" in 2005, that is, on the fifth day after surgery, total
bilirubin>50 μ mol/L (2.9 mg/dl) and prothrombin ratio<50% (INR>1.7) are met simultaneously.
The Sensitivity and specificity of this standard are 69.6% and 98.5% respectively , which was
confirmed as an effective predictor of death after Hepatectomy in 2009 . The "Edinburgh
Standard" proposed by Schindl et al. in 2005 is to divide the severity of PHLF according to
Hematology examination and clinical observation, which can be divided into
none/mild/moderate/severe . Mullen et al. proposed a peak postoperative bilirubin level>120 μ
Mol/L), which can predict the death related to Liver failure, with a sensitivity of 93.3% and
a specificity of 94.3% . At present, the 2011 definition of the International Research Group
on Hepatosurgery (ISGLS) has been widely used as a standard to describe PHLF. According to
the international normalized ratio (INR), hyperbilirubin and other test indicators five days
after hepatectomy, and in combination with liver function, kidney function, respiratory
function, whether special assessment and special clinical treatment are required, the
severity of Liver failure in patients with cirrhosis after Hepatectomy is divided into A, B C
has three levels . The reported incidence of PHLF varies greatly, ranging from 0.7% to 34% ,
but recent reports have more commonly described it as between 8% and 12% . PHLF is an
important cause of death after Hepatectomy. In a large study, 70% of all patients who died
after liver resection met the PHLF criteria, while over 50% of patients had PHLF as the
direct cause of death. Moreover, nearly half of hospital deaths caused by PHLF occur within
30 days after surgery. In addition, the management cost of these postoperative complications
is high . Although there are already many treatment strategies that can save patients with
PHLF, the evidence for these treatment methods is still limited, and only a few conventional
methods are available for clinical use.
Many preoperative factors may lead to PHLF. These have been extensively discussed in other
studies, including patient factors, disease pathology, intraoperative characteristics, and
postoperative course, but the most important factor that may affect the occurrence of PHLF is
the condition of the liver. On the one hand, it is the insufficient amount of remaining liver
tissue, accompanied by a decrease in liver regeneration ability in patients with cirrhosis.
The morphology, structure, and physiological function of regenerated liver cells are
incomplete, which can also affect the function of liver cells. At the same time,
postoperative liver reperfusion loss can also lead to insufficient liver functional liver
cell count. On the other hand, surgery directly leads to damage to the hepatic vascular
structure, changes in microcirculation structure, excessive inflammatory response after
surgery leading to liver microcirculation disorders, liver hypoperfusion, and further
exacerbating liver injury. Therefore, precise assessment of liver reserve function and
monitoring of liver microcirculation disorders during the perioperative period are of great
significance for selecting reasonable treatment methods, grasping the safe range of liver
resection, and reducing the incidence of postoperative liver failure in patients.
Liver reserve function refers to the additional compensatory potential that the liver can
mobilize in response to increased physiological load. In the pathological state of liver
damage, the liver reserve function needs to meet the Functional requirement of body
metabolism, immunity and detoxification, as well as the needs of liver tissue repair and
regeneration. The reserve function of the liver mainly depends on the number of functional
liver cell populations and the integrity of their organizational structure. For decades, the
Child-Pugh score has been an important prognostic tool for patients with chronic liver
disease, used to stratify preoperative risk and to some extent remains a guiding factor for
clinical decision-making. The MELD score (the "end stage liver disease model") can better
predict the prognosis of chronic liver disease. And MELD score is related to the early
prediction of incidence rate and mortality after Hepatectomy. Recently, the albumin bilirubin
(ALBI) score and its improvement have been proposed as an objective and evidence-based
clinical liver function assessment method. It has been proved to be a reliable assessment of
liver dysfunction in many studies , and is found to be superior to Child Pugh score in
predicting the outcome after Hepatectomy for liver cancer. The remaining liver volume (FLR)
is achieved by calculating the proportion of remaining liver tissue in the total liver
volume. To avoid PHLF, based on experience, it is recommended that the FLR be at least 20% of
the standard total liver volume, as the remaining parenchyma is normal . In addition, Truant
et al. found that patients with residual liver volume (RLV=FLR) related to body weight less
than 0.5% of their body weight had a significant risk of postoperative liver dysfunction and
death. If the liver is damaged through chemotherapy or existing liver diseases (such as
cirrhosis), it is necessary to increase FLR by at least 30% and 40%, respectively .
However, although liver volume itself is important, it may not necessarily be related to
liver function. There are inherent limitations to liver capacity and Child Pugh score.
Compared to simple calculations of residual liver volume (FLR), the evaluation of functional
liver residual volume is better. Among the numerous tests to evaluate functional liver
capacity, indocyanine green clearance (ICG R15) is the most commonly used test, which can
minimize PHLF and mortality after Hepatectomy. In a large single center study, Professor
Yamin strictly applied bilirubin based algorithms and stratified them based on ICG clearance
rate, not only deciding which patients to undergo resection, but also deciding which type of
resection to perform. In a period of 10 years, excellent results have been achieved, with
only one patient having an extremely low mortality rate out of over a thousand resection
procedures. However, there are some limitations to ICG clearance, especially in patients with
perioperative jaundice and patients with impaired hemodynamics. Another aspect that reflects
the reserve function of the liver is the integrity of the tissue structure, which directly
determines the microcirculation structure of the liver. The complex functions of liver
biosynthesis, metabolism, detoxification, and host defense are closely dependent on a sound
liver microcirculation. Research has shown that microcirculation disorders are one of the
important pathogenesis of chronic liver disease, running through the entire disease
development process. Improving liver microcirculation is beneficial for the recovery of liver
function and helps to prevent and delay the formation of liver fibrosis and cirrhosis. The
Guidelines for the Diagnosis and Treatment of Liver failure (2012 Edition) mentioned that all
kinds of chronic liver disease patients have different degrees of liver microcirculation
disorders. Due to the increase of blood viscosity and the slowing of blood flow, the blood
perfusion and oxygen supply of microcirculation will inevitably be affected. It is difficult
for blood to enter and exit the liver, and the nutritional supply to liver cells cannot be
guaranteed, leading to further damage to liver cells, resulting in a vicious cycle. The
nutrients absorbed by the gastrointestinal tract are difficult to enter the liver, resulting
in indigestion; Drugs absorbed in the bloodstream are difficult to enter the liver and come
into contact with liver cells, making it difficult to effectively exert drug efficacy;
Metabolic waste is difficult to excrete from the liver, becoming toxins that remain in the
liver, leading to liver cell damage and accelerating the progression of liver disease. At
present, the main observation indicator reflecting liver microcirculation is effective liver
blood flow, which is also the "functional liver blood flow" studied in recent years.
Effective Hepatic Blood Flow (EHBF) refers to the blood flow of the liver that comes into
contact with liver cells and undergoes material exchange and metabolic function. Under the
condition of liver cirrhosis, due to changes in liver microcirculation structure and the
establishment of collateral circulation, there is arteriovenous shunt inside and outside the
liver. The effective blood flow of the liver (functional liver blood flow) is much lower than
the total liver blood flow (physical liver blood flow), and the clearance function of the
liver also decreases accordingly. The literature reports that using indocyanine green or
D-sorbitol as reagents for EHBF determination showed a significant decrease in EHBF in
patients with liver cirrhosis compared to normal individuals. Another study showed that EHBF
in patients with chronic liver failure was significantly lower than that in patients with
decompensated cirrhosis, and EHBF was closely related to the severity of HBV infection in
patients with chronic liver failure, which can be used to predict their 90 day mortality
rate. Therefore, EHBF is considered to reflect liver reserve function and also a marker of
liver ischemia.
In order to improve the safety of liver resection, establishing a safe and effective liver
resection decision tree based on existing experience and data has always been a research
direction in liver and gallbladder surgery. In order to avoid Liver failure after
Hepatectomy, we should carefully consider whether to retain sufficient functional liver
volume before operation. However, there is no uniform standard for clinical hepatobiliary
Surgeon to evaluate liver reserve function before Hepatectomy. Each center proposes a variety
of hepatectomy decision systems based on Scientific theory and the center's practical
experience. At present, most of them refer to the Makuuchi standard of University of Tokyo in
Japan, the University of Zurich standard in Europe, the consensus decision tree of Chinese
experts on hepatectomy, in addition to Hong Kong, Fudan Zhongshan and other standards.
The evaluation of liver reserve function proposed by the above standards refers to the Child
Pugh score, ICG15 minute retention rate (R15), or ICG plasma clearance rate (ICGK). However,
the Child Pugh score, ICGR15, and ICGK only reflect the number of functional liver cell
populations, and the integrity of liver tissue structure is not directly reflected. EHBF may
be able to supplement and improve liver reserve function.
To sum up, previous studies have shown that liver reserve function is related to Liver
failure (PHLF) after Hepatectomy. The retrospective study of the Chinese expert consensus
decision tree for hepatectomy also shows the safety and effectiveness of the decision tree in
the case of expanded hepatectomy indications, but there is a lack of forward-looking research
to evaluate it. Therefore, this study intends to evaluate the safety and effectiveness of
Hepatectomy under the guidance of the consensus decision tree of Chinese experts through
prospective research.
