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\begin{document}

\title{liver dysfunction after endoscopic esophageal variceal ligation: A case
report and literature review}



\author[1]{xiaojun ren}%
\author[1]{Zhao-Hong Shi  }%
\author[2]{ Ying-Xia Cheng}%
\author[3]{Yun Luo}%
\affil[1]{Hubei University of Chinese Medicine}%
\affil[2]{Ningxia Medical University}%
\affil[3]{Dazhou Integrated TCM and Western Medicine Hospital}%


\vspace{-1em}



  
  \date{June 15, 2024}


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\textbf{Introduction:}

Since its introduction in 1986\textsuperscript{{[}1{]}}, endoscopic
variceal ligation (EVL) has gained wide acceptance in clinical practice
due to its simplicity, short duration, and low complication
rates\textsuperscript{{[}2, 3{]}}. Clinical guidelines in many countries
have been recommended EVL as the first-line treatment for esophageal
varices in liver cirrhosis\textsuperscript{{[}4-6{]}}. However, there
have been reports of potential adverse events associated with EVL. These
include esophageal stenosis, ulcer bleeding, esophageal perforation,
esophageal hematoma, pneumonia, and spontaneous bacterial
peritonitis\textsuperscript{{[}7-10{]}}. Although rare, cases of liver
dysfunction following EVL have also been reported. In this paper, we
present the case of a 50-year-old male patient diagnosed with alcoholic
cirrhosis and esophageal variceal rupture and bleeding. He underwent
emergency EVL for hemostasis at our hospital. Subsequently, he developed
liver dysfunction. The patient's condition improved following active
conservative treatment in internal medicine and DPMAS+PE therapy.

\textbf{The study was approved by the Ethics Committee of Dazhou
Hospital of Integrative Medicine. Written informed consent was obtained
from the patient's family.}

\textbf{Case report:}

A 55-year-old male patient with a history of more than 30 years of
alcohol consumption, averaging about 100-150ml per day, was presented.
Six years ago, he was diagnosed with alcoholic liver disease due to
liver dysfunction and received symptomatic treatment including
abstinence and liver protection at our hospital. Subsequently, he has
been regularly followed up at the Digestive and Liver Disease
Department. Three years ago, he was admitted to our hospital due to
hematemesis. Gastroscopy revealed ruptured and bleeding esophageal
varices. After undergoing EVL for hemostasis and receiving comprehensive
internal medicine treatment, he showed improvement and was discharged.
Post-discharge, he was prescribed oral propranolol (10mg twice a day) to
reduce portal vein pressure. On January 26, 2023, the patient
experienced recurrent hematemesis after consuming solid food, leading to
his emergency admission to our hospital. Routine and biochemical
examinations revealed the following: WBC: 4.67X10\^{}9/L, RBC:
3.28X10\^{}12/L, HGB: 88g/L, PLT: 26X10\^{}9/L, AST: 104U/L, ALT: 31U/L,
DBIL: 24.2umol/L, TBIL: 43.1umol/L, PT: 16.6sec, ALB: 25.1g/L, APTT:
34.5sec, PTA: 46.6\%, INR: 1.46, and FIB: 1.020g/L. Computerized
tomography revealed liver cirrhosis, splenomegaly, a small amount of
ascites in the abdominal cavity, and esophageal varices. Emergency
gastroscopy confirmed the presence of ruptured and bleeding esophageal
varices, leading to the clinical diagnosis of alcoholic liver cirrhosis
with decompensated esophageal variceal rupture (Child-Pugh B). With
consent obtained from the patient and his family members, emergency
endoscopic esophageal variceal ligation was performed (refer to Figure I
for the specific procedure). Post-surgery, the patient underwent
fasting, received somatostatin to reduce portal vein pressure, underwent
cefoperazone sodium treatment for anti-infection, received a 400ml
transfusion of suspended red blood cells to correct anemia, and was
provided compound amino acids (3AA) with various vitamins for
symptomatic nutritional treatment following improvement.

On the third day following the surgery (January 30, 2023), the patient
exhibited yellowing of the skin and sclera. The results of blood tests,
liver function, and coagulation function showed deterioration. The
findings were as follows: WBC: 5.73X10\^{}9/L; RBC: 2.79X10\^{}12/L;
HGB: 76g/L; PLT: 36X10\^{}9/L; AST: 222U/L; ALT: 69U/L; DBIL: 219umol/L;
TBIL: 309umol/L; PT: 23.5sec; APTT: 49.9sec; PTA: 29.3\%; INR: 2.10;
FIB: 1.52g/L. The clinical diagnosis was acute-on-chronic liver failure
(type B). The patient was advised to observe bed rest and received
magnesium isoglycyrrhizinate injections for liver protection, Transmetil
(Ademetionine 1,4-Butanedisulfonaate) injections to manage jaundice, a
300ml infusion of fresh frozen plasma, and a 400ml intravenous drip of
suspended red blood cells to improve coagulation function and address
anemia. Two days later (February 2, 2023), a re-examination of blood
routine and biochemical indicators revealed the following values: WBC:
6.53x10\^{}9/L; RBC: 3.0x10\^{}12/L; HGB: 81g/L; PLT: 49x10\^{}12/L;
AST: 48U/L; ALT: 131U/L; DBL: 278.4umol/L; TBL:435u/L; PT: 21sec; APTT:
50.4sec; PTA: 34\%; FIB: 2.11g/L. However, bilirubin levels continued to
rise, and the patient showed poor response to the comprehensive internal
medicine treatment. With the patient's and family's consent, DPMAS+PE
treatment was administered on February 3, 2022. One day later (February
4, 2023), a blood re-examination showed the following results: WBC:
6.17x10\^{}9/L; RBC: 2.63x10\^{}12/L;HGB:72g/L; PLT:48x10\^{}12/L;
AST:79U/L; ALT: 37U/L; DBL:196.3umol/L; TBL :316.0u/L; PT:17.4sec;
APTT:41.6sec; PTA:43.7\%; FIB:2.040g/L. DPMAS+PE treatment was
administered once again on February 6th, 2023. The subsequent blood
routine and biochemical indicators, reviewed on February 7th, 2023,
showed the following values: WBC: 5.53x10\^{}9/L; RBC: 2.91x10\^{}12/L;
HGB: 77g/L; PLT: 53x10\^{}12/L; AST: 88U/L; ALT: 43U/L; DBL:
183.9umol/L; TBL: 279.3u/L; PT: 18.7sec; APTT: 40.6sec; PTA: 39.7\%;
FIB: 1.870g/L. The patient's symptoms of poor appetite and fatigue had
significantly improved. On February 9th, 2023, a blood test showed the
following results: WBC: 5.99x10\^{}9/L, RBC: 2.93x10\^{}12/L, HGB:
77g/L, PLT: 55x10\^{}12/L, AST: 99U/L, ALT: 58U/L, DBL: 193.5umol/L,
TBL: 284.2u/L, PT: 19.3sec, APTT: 42.2sec, PTA: 38.1\%, FIB: 1.620g/L.
The patient continued to receive basic treatment such as liver
protection and jaundice relief. Additionally, due to the presence of
anemia, another transfusion of suspended red blood cells (400ml) was
administered to address the anemia. On February 12th, 2023, a blood test
showed the following results: WBC: 8.36x10\^{}9/L, RBC: 3.23x10\^{}12/L,
HGB: 83g/L, PLT: 47x10\^{}12/L, AST: 95U/L, ALT: 81U/L, DBL:
185.2umol/L, TBL: 267.6u/L, PT: 20.1sec, APTT: 45.1sec, PTA: 36.1\%,
FIB:1.270g/L. Considering the patient's persisting symptoms of fatigue
and poor appetite, as well as the prolonged elevation of bilirubin
levels, DPMAS+PE treatment was administered again on February 13th,
2023. Two days later (February 15th), a review of blood routine and
biochemical indicators revealed the following values: WBC:
9.05x10\^{}9/L; RBC: 3.22x10\^{}12/L; HGB: 82g/L; PLT: 46x10\^{}12/L;
AST: 58U/L; ALT: 55U/L; DBL: 142.3umol/L; TBL: 197.5u/L; PT: 17.2sec;
APTT: 38.4sec; PTA: 44.4\%; FIB: 1.680g/L. Two days later (February
17th), the blood routine and biochemical indicators were reviewed again,
showing the following values: WBC: 5.66x10\^{}9/L; RBC: 3.14x10\^{}12/L;
HGB: 80g/L; PLT: 34x10\^{}12/L; AST: 58U/L; ALT: 66U/L; DBL:
112.8umol/L; TBL: 148.1u/L; PT: 18.4sec; APTT: 42.7sec; PTA: 40.6\%;
FIB: 1.210g /L. The patient's condition remained relatively stable, and
maintenance treatment, including liver protection and jaundice relief,
was continued during this period. Another transfusion of suspended red
blood cells (400ml) was administered to address the anemia.

Two days later, on February 20th, a follow-up blood routine and
biochemical analysis was conducted, revealing the following results:
WBC: 5.95x10\^{}9/L; RBC: 3.87x10\^{}12/L; HGB: 96g/L; PLT:
34x10\^{}12/L; AST: 88U/L; ALT: 96U/L; DBL: 114.6umol/L; TBL: 159.2u/L;
PT: 17.1sec; APTT: 36.7sec; PTA: 44.7\%; FIB: 1.640g/L. With the
patient's condition being stable, the patient and their family requested
discharge due to the high medical expenses. They were informed that the
patient should have a follow-up outpatient visit at the hospital where
the author is located after discharge. Subsequent telephone follow-ups
conducted after March indicated that the patient's general condition was
good, and they were able to engage in light physical activity.

\textbf{Discussion:}

Since its introduction in 1986, EVL (Endoscopic Variceal Ligation) has
been widely recommended as the first-line treatment for esophageal
varices in liver cirrhosis by clinical guidelines in numerous countries.
When compared to EIS (Endoscopic Injection Sclerotherapy), EVL
demonstrates significant superiority in terms of rebleeding rate,
variceal eradication rate, and complications\textsuperscript{{[}1-6{]}}.
Consequently, an increasing number of clinicians consider EVL as the
preferred treatment for patients experiencing esophageal variceal
rupture and bleeding. Reported complications of EVL mainly encompass
esophageal stenosis, ulcer bleeding, esophageal perforation, esophageal
hematoma\textsuperscript{{[}7-9{]}}, pneumonia, and spontaneous
bacterial peritonitis\textsuperscript{{[}10-12{]}}. However, there have
been few reports documenting liver function failure following EVL
surgery. Through a comprehensive literature review, we discovered that
only one case of elevated bilirubin levels with subsequent liver
dysfunction after EVL surgery has been documented thus far. This case
involved a 51-year-old female patient with primary biliary cholangitis
(PBC) and esophageal variceal rupture and bleeding, who underwent EVL
treatment. Following the procedure, the patient experienced an increase
in bilirubin levels from 4.0mg/dL to 9.5mg/dL, ultimately necessitating
liver transplantation due to the worsening of liver function
failure\textsuperscript{{[}13{]}}.

The mechanism behind liver function failure after EVL surgery remains
unclear. In the context of cirrhosis, both hepatic and splanchnic
systemic oxygen uptake (VO2) are reduced\textsuperscript{{[}14, 15{]}}.
Our hypothesis suggests that the cause of liver failure in patients
after EVL may be attributed to increased portal pressure, decreased
cardiac output, and reduced oxygen delivery following the procedure.
Previous studies have reported that 68\% of patients undergoing
endoscopic variceal ligation experience an elevation in portal vein
pressure\textsuperscript{{[}16{]}}. It is postulated that the sudden
rise in portal vein pressure could exacerbate liver congestion, impair
oxygen utilization by liver cells, and subsequently lead to liver cell
necrosis. However, a study conducted in 2003 revealed no significant
change in the portal vein pressure gradient before and after EVL surgery
in patients with liver cirrhosis and esophageal variceal rupture and
bleeding\textsuperscript{{[}17{]}}. Consequently, further investigation
is required to explore whether an increase in portal vein pressure
occurs after EVL surgery.

As early as 1996, reports emerged highlighting a related phenomenon
wherein EVL surgery may exacerbate liver tissue ischemia and hypoxia.
This study observed a decrease in cardiac output and oxygen delivery
immediately after EVL surgery, although the underlying causes and
implications were not fully understood at the
time\textsuperscript{{[}18{]}}. This hypoxic condition is particularly
pronounced in patients with varicose veins and anemia. Research has
shown that patients with liver cirrhosis exhibit a high dynamic
circulation, which enhances oxygen delivery but impairs the uptake and
utilization of oxygen by tissues, resulting in sustained liver cell
hypoxia\textsuperscript{{[}19{]}}. Furthermore, all tissues of patients
with liver cirrhosis experience a certain degree of hypoxia due to
arteriovenous shunting\textsuperscript{{[}20{]}}. Therefore, a sudden
decrease in cardiac output and oxygen delivery could further intensify
liver cell hypoxia, leading to acute massive necrosis of liver
cells.Overall, the precise mechanisms underlying liver function failure
after EVL surgery necessitate further investigation. The potential
impact of increased portal pressure, reduced cardiac output, oxygen
delivery, and the exacerbation of liver cell hypoxia requires
comprehensive exploration. Future research should focus on elucidating
these mechanisms to enhance our understanding and potentially develop
strategies for mitigating liver function failure following EVL surgery.

Furthermore, there have been reports suggesting the potential
involvement of endogenous nitric oxide in the regulation of systemic
hemodynamics in patients with compensated cirrhosis. Serum nitrate and
nitrite, which are metabolic byproducts of endogenous nitric oxide,
exhibit a sudden decrease in concentration in patients after
EVL\textsuperscript{{[}21, 22{]}}. Previous studies have demonstrated
that nitric oxide can alleviate ischemia-reperfusion injury of the liver
and expedite the recovery of liver function\textsuperscript{{[}23{]}}.
Nitric oxide's protective effects on liver tissue may play a role in the
context of EVL surgery, although further research is required to
investigate the specific mechanisms and implications of nitric oxide
modulation in this setting.

It has been reported in studies that compared to patients with
Child-Pugh A/B, patients with Child-Pugh C cirrhosis exhibit higher
rates of rebleeding and mortality following
EVL\textsuperscript{{[}24{]}}. In the case of our patient, their liver
function reserve was evaluated as Child-Pugh B upon admission. However,
after undergoing emergency EVL, the patient experienced a significant
increase in bilirubin levels and developed coagulation dysfunction. We
speculate that these effects may be attributed to the blockage of
collateral circulation caused by acute bleeding and the impact of EVL
surgery, particularly in the context of poor liver function reserve.
This could exacerbate liver congestion symptoms. Additionally, the
decrease in cardiac output further intensifies the ischemia and hypoxia
experienced by liver cells, ultimately leading to acute necrosis and
liver failure. It is important to note that the occurrence of liver
failure after EVL surgery is relatively rare, and our understanding of
its underlying mechanism is based on plausible pathological and
physiological considerations. Further research is required to delve into
the intricate mechanisms involved and provide conclusive evidence.

\textbf{Reference}

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\textbf{Figure I}\selectlanguage{english}
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