Elabd, N., Mohammed, H., Abd Alrahman, A., Eid, M., Seleem, H. (2022). Risk of Surgery in Patients with Liver Cirrhosis. Afro-Egyptian Journal of Infectious and Endemic Diseases, 12(4), 367-382. doi: 10.21608/aeji.2022.166302.1258
Naglaa S Elabd; Hossam I Mohammed; Amal I Abd Alrahman; Mohamed A Eid; Hosam El-Din M Seleem. "Risk of Surgery in Patients with Liver Cirrhosis". Afro-Egyptian Journal of Infectious and Endemic Diseases, 12, 4, 2022, 367-382. doi: 10.21608/aeji.2022.166302.1258
Elabd, N., Mohammed, H., Abd Alrahman, A., Eid, M., Seleem, H. (2022). 'Risk of Surgery in Patients with Liver Cirrhosis', Afro-Egyptian Journal of Infectious and Endemic Diseases, 12(4), pp. 367-382. doi: 10.21608/aeji.2022.166302.1258
Elabd, N., Mohammed, H., Abd Alrahman, A., Eid, M., Seleem, H. Risk of Surgery in Patients with Liver Cirrhosis. Afro-Egyptian Journal of Infectious and Endemic Diseases, 2022; 12(4): 367-382. doi: 10.21608/aeji.2022.166302.1258
1Department of Tropical Medicine, Faculty of Medicine ,Menoufia University, Menoufia, Egypt.
2Department of Anesthesia, Faculty of Medicine - Menoufia University, Menoufia, Egypt.
3M.B. B. Ch., El-Helal Orthopedic and General Surgery Hospital, Cairo
Abstract
Background and aim: Chronic liver disease patients often undergo surgery for indications other than liver transplantation and may face increased perioperative risk due to surgical and anesthesia-related complications. The current study's objectives were to assess the risk of surgery in cirrhotic patients and to identify various variables that influence postoperative outcomes. Methods: 231 participants underwent non-hepatic surgery under general anesthesia categorized into 117 cirrhotic patients and 114 non-cirrhotic (controls). All participants were subjected to complete clinical and laboratory evaluations (pre-operative, and post-operative) with an assessment of postoperative outcomes. For cirrhotic patients, the severity of liver disease was assessed by Child-Pugh and MELD scores. Results: In cirrhotic patients, hepatic causes are considerably the cause of not having surgery, additionally, the majority of patients who underwent surgery had Child-Pugh scores of A or B (42.7 % and 44.5%,respectively), whereas only 12.8% had Child-Pugh C. Hepatic complications including HE, decompensation, and SBP were more frequent in patients with CTP grades B and C than those with grade A. Postoperative mortality significantly associated with higher white blood cells (WBCs), serum creatinine, and MELD score (p=0.001, 0.049, and 0.002,respectively), and lower serum albumin (p=0.028). AUC for WBCs, serum creatinine, MELD score, and serum albumin was 0.958, 0.759, 0.963, and 0.765 respectively at cut-off >11.5, >1.2, ≤2.3, and >15 respectively. Conclusion: Operative complications (hepatic and non-hepatic)are more frequent in patients with CTP grades B and C than those with grade A. Postoperative mortality significantly associated with higher WBCs, serum creatinine, and MELD score, and lower serum albumin.
Highlights
Chronic liver disease patients often undergo surgery for indications other than liver transplantation and may face increased perioperative risk due to both surgical and anesthesia-related complications.
In cirrhotic patients, hepatic causes are considerably the cause of not having surgery, additionally, the majority of patients underwent surgery had a Child Pugh score of A or B, whereas only few had Child Pugh C.
Hepatic and non-hepatic complications are common in cirrhotic patients including decompensation.
Postoperative mortality significantly associated with higher WBCs, serum creatinine, and MELD score in addition to lower serum albumin.
Cirrhotic patients need distinctive perioperative care. Optimal perioperative care could decease such complications.
The final stage of the liver's progressive fibrosis is liver cirrhosis. Liver cirrhosis can result from a variety of assaults, most notably chronic viral hepatitis (HBV and HCV), metabolic disorders, in addition to alcoholic and nonalcoholic steatohepatitis [1]. According to estimates, liver cirrhosis ranks as the 13th most common cause of death worldwide. In 2010, it was noticed that liver cirrhosis gave a share in 31 million or 1.2% of global disability-adjusted life years (DALYs). Worldwide, liver cirrhosis was assorted as 23rd leading cause of disease burden [2].
Despite having the highest rate of HCV infection in the world for years, Egypt has made the biggest strides toward the disease's eradication [3]. The emergence of highly effective all-oral, interferon free, direct acting antiviral (DAA) medications for patients with cirrhosis has transformed the treatment options for HCV patients and the majority of patients can now achieve viral clearance even with the presence of cirrhosis
Patients with cirrhosis are living longer with more advanced disease thanks to better medical and surgical therapy, despite global increases in the prevalence of chronic liver disease (CLD) caused by viral hepatitis and nonalcoholic steatohepatitis (NASH). Consequently, they are at risk for other diseases and morbidities that cirrhotic patients might not have previously experienced [4].
Surgery is frequently performed on patients with chronic liver disease for purposes other than liver transplantation, and may face increased perioperative risk due to both anesthesia- and surgery-related issues. In their final two years of life, 10% of patients with severe liver disease need a surgical procedure other than a liver transplant. Surgery may also be performed on people with undiagnosed CLD, with cirrhosis only being identified intraoperatively based on a macroscopic evaluation [5] any surgical procedure in undetected cirrhotic patients could have disastrous consequences.
CLD patients undergoing surgery have substantially higher rates of Surgery-related complications and mortality. Additionally, ICU admission, mechanical ventilation, and renal replacement therapy have all been demonstrated to independently increase hospital mortality among patients with CLD [6].
The risk of surgery in patients with liver cirrhosis vary depending on the severity of liver disease, the clinical setting as well as type of surgery. The severity and nature of the underlying CLD as well as the type of surgery have a significant impact on postoperative outcomes. The Child-Turcotte-Pugh (CTP) score has been the primary indicator of surgical risk in cirrhotic patients for over 30 years, but more recent research indicates that the Model for End-Stage Liver Disease (MELD) score may be more accurate [7]. The current study's objectives were to assess the risk of surgery in patients with liver cirrhosis and to identify various variables that may influence the outcome of surgery in these patients.
METHODS
This prospective case-control research was carried out in Tropical Medicine and Anesthesia Departments, Faculty of Medicine, Menoufia University in collaboration with El-Helal Orthopedic and General Surgery Hospital, Cairo between September 2019 to March 2021. This study was performed on 231 participants who underwent non hepatic surgery under general anesthesia. Their work up included preoperative evaluation for their fitness of operations, intra operative event and their follow up & outcome after surgery.
Based on the presence or absence of CLD study participants were grouped into one of two groups; Group I: included 117 patients with evidence of liver cirrhosis they were 71 (60.7%) males and 46 (39.3%) females with mean age (53.00±24.04) ranging from 36 to 70 and Group II: 114 healthy participants without any evidence (clinical, laboratory and imaging) of liver disease as controls, they were 66 (57.9%) males and 48 (42.1%) females with mean age (50.50± 24.75). Preoperative management in patients with established liver illness attempts to identify the underlying cause, optimize liver function by enhancing nutritional status, correct coagulopathy, and treat HE, as well as portal hypertension and ascites.
For all participants, preoperative assessment including history, clinical evaluation, laboratory, and imaging evaluation was performed. History of smoking and other co-morbidities (history of DM and HTN and their treatments) was assessed. Besides, history of upper GIT bleeding (hematemesis, melena or bleeding per rectum) and history of upper GIT endoscopy. Assessment of drug history including antiviral therapy (HCV, HBV), diuretics and medication to control coagulopathy. Full clinical evaluation focusing on signs of liver affection including bleeding tendency, jaundice, edema of lower limbs, and history of hepatic encephalopathy.
Preoperative laboratory evaluation: laboratory investigations comprised complete blood count (CBC), liver function tests [prothrombin time, the international normalized ratio (INR), alanine transferase (ALT), aspartate transferase (AST), serum albumin, total & direct bilirubin], kidney function tests and serum electrolytes. Viral markers including HCV Ab, HBVsAg and HIV Ab were done by ELISA.
Preoperative radiological evaluation: Abdominal ultrasonography was done for all participants for evaluating liver size, ecohopattern and portal vein (diameter and patency), evaluating spleen size, echopattern, focal lesions, and perisplenic collaterals, assessing the presence and grading of ascites, as well as evidence of echoes, adhesions or loculations. Other radiological assessments were required for patients according to type and indication of surgery.
Preoperative assessment of liver disease severity: For cirrhotic patients we estimated liver disease severity by Child-Turcotte-Pugh score (CTP) and MELD scores, we calculated Child-Turcotte-Pugh score (CTP) that depends on assessment of patient’s ascites, serum albumin, total bilirubin, prothrombin time and history of hepatic encephalopathy [8], and MELD score was calculated by using the following equation:
Preoperative classification of surgery: We classified cirrhotic and non-cirrhotic patients regarding time of operative intervention into: elective surgery and emergency surgery. [10]
Intra-operative assessment including: Type of anesthetic agent, Duration of operation, Intra operative complication (bleeding- anoxia, etc…), and Necessity for blood transfusion, number of units, fresh frozen plasma and platelet transfusion during operation.
Post-operative outcome assessment: The need for intensive care unit admission post operatively, clinical assessment for complications which may be either hepatic or non-hepatic complications. Hepatic complications including signs and symptoms of severe hepatic decompensation (hepatic encephalopathy (HE), jaundice, ascites, hematemesis and spontaneous bacterial peritonitis (SBP). Non hepatic complications included chest infection, surgical complications and others. Laboratory assessment post operatively and follow up included CBC, Liver profile including serum bilirubin, ALT, AST, and albumin, Prothrombin time and concentration (PT & PC) and international normalized ratio (INR), blood urea and serum creatinine, serum electrolytes.
Postoperative mortality: Postoperative mortality was reported and was classified into Hepatic causes as a result of sever liver decompensation (Hematemesis, hepatic encephalopathy, SBP and HRS) or non-hepatic causes as chest infection and surgical complications.
Statistical analysis of the data:
Data were collected, tabulated and statistically analyzed using an IBM compatible personal computer with Statistical Package for the Social Sciences (SPSS) version 23 (SPSS Inc. Released 2015. IBM SPSS statistics for windows, version 23.0, Armnok, NY: IBM Corp.). Two types of statistical analysis were performed: Descriptive statistics included, mean (x) and standard deviation (SD) and analytic statistics included chi-square test (χ2) Student's t-test, Inter-group comparison, P value
RESULTS
Based on the presence or absence of CLD study participants were categorized into one of two groups; Group I included 117 patients with evidence of liver cirrhosis and Group II comprised 114 healthy participants without any evidence of liver disease as controls.
Table 1 summarized the comparison between the two studied groups regarding the demographic and clinical data: cirrhotic patients ranged in age between 36- 70 years with a mean age of 53.00±24.04 years and non-cirrhotic patients ranged in age between 33-68 years with a mean age 50.50± 24.75 years. We noticed that the mean of age as well as gender distributions did not differ between the two groups. Smoking history, hypertension, and diabetes mellitus were not significantly different between the two groups in terms of the existence of comorbid disorders (p = 0.974, 0.814, and 0.874 respectively). However, only cirrhotic patients reported history of hepatic encephalopathy (14.5%), hematemesis and/or melena (10.3%) and bleeding from other sites including epistaxis, bleeding gums (8.5%)
Concerning the history of previous upper GIT endoscopy; esophageal Varices and or PHG were reported in 24.8% of cirrhotic patients, and gastritis was notified in 15.4% and 8.8 % in cirrhotic and non-cirrhotic respectively with a statistically significant difference (p <0.001). Regarding the general examination; pallor was considerably different between the two groups (p <0.001). Jaundice, flapping tremors, and lower limb edema were detected in 11.1%, 6.8%, and 29.1% respectively in cirrhotic patients (table 1).
Table 1 demonstrates that, ascites was mild to moderate in 12% of cases and massive in 2.6%, whereas 85.4% of cirrhotic patients did not have ascites. Hepatomegaly and splenomegaly were also seen in 53.8% and 63.2% of cases, respectively. Umbilical hernias were more frequent in cirrhotic patients than in non-cirrhotic patients (p = 0.021).
According to the preoperative laboratory investigations, table 2 and figures 1A & 1B reveal that there was a statistically significant difference in Hb concentration, platelet count, ALT, AST, serum albumin, total bilirubin, INR, and blood urea between the cirrhotic and non-cirrhotic patient groups. The cirrhotic group as compared to the non-cirrhotic group, Hb concentration, platelets count, and serum albumin were significantly lower, and ALT, AST, total bilirubin, and blood urea were significantly higher. Regarding the total leucocyte count, serum creatinine, serum Na or serum K, and INR, there was no discernible difference between the patient groups.
The indications for surgery and classification of surgery regarding urgency either elective or emergent of the studied groups were presented in supplementary table 1. Regarding patients who underwent surgery or did not, as well as the types of surgery (elective and emergency), there were a statistically non-significant differences between the cirrhotic and non-cirrhotic groups (p>0.05). Even though there were no statistically significant differences between the cirrhotic and non-cirrhotic patients who underwent surgery (operated) or did not (non-operated) (p = 0.074), and their types (elective and emergency), there was still a tendency for cirrhotic patients to be not operated as shown in supplementary table 2. In cirrhotic patients, hepatic causes were considerably linked to the explanation of not having surgery (supplementary table 3). The Child Pugh score and grading in cirrhotic patients are shown in figure 1C. The majority of patients had a Child Pugh score of A or B (42.7 or 44.5, respectively), whereas only 12.8 had a Child Pugh C.
Only cirrhotic patients required preoperative plasma (40.2%) or platelet transfusion (7.84%) or urgent upper endoscopy (9.8%), in addition, preoperative blood transfusion and ICU admission were more common in cirrhotic patients (p < 0.001 and 0.025 respectively). These patients also required urgent intraoperative measures (plasma or platelet transfusion) and postoperative ICU admission (27.45%) (table 3). The requirement for post-operative ICU admission was greater in emergency procedures, and there was a statistically significant difference between patients with elective and emergency operations in both cirrhotic and non-cirrhotic groups (p = 0.012 and 0.003, respectively). Additionally, patients with cirrhosis who were merely undergoing emergency procedures needed platelet transfusions. Contrarily, there was no statistically significant difference in the need for intra-operative blood transfusions between patients undergoing elective or emergency procedures in the cirrhotic and non-cirrhotic groups (p>0.05) as displayed on supplementary table 2.
According to Table 4, the mean values of TLC, blood urea, and serum creatinine significantly increased in the cirrhotic group while the mean values of serum albumin, INR, and Na significantly decreased post-operatively compared to their pre-operative levels. In non-cirrhotic patients, there was significant increase in mean values of TLC and platelets count with significant decrease in mean values of Hb concentrations and serum Na post-operative compared to pre-operative values, however, no significant changes were noted regarding liver functions (figures 1D and 1E).
Regarding the prevalence of post-operative morbidity and mortality, there was a statistically significant difference between the cirrhotic and non-cirrhotic groups (p = 0.016 and 0.048), with more frequent adverse outcomes being detected in the cirrhotic group (figure 1F).
Concerning the post-operative health problems in the cirrhotic group, there was a significant difference between patients who underwent elective and emergency procedures, with elective procedures experiencing more frequent complications either hepatic or non-hepatic and only emergency procedures experiencing post-operative mortality. Hepatic complications including HE, decompensation, SBP, and melena were more frequent in patients with Child Pugh grade B and C than those with grade A. In non-cirrhotic patients, there was a statistically non-significant difference between elective and emergency operations regarding post-operative morbidity, but only emergency operations were associated with post-operative mortality (figures 2A-D).
Preoperative data from the cirrhotic group were compared between survived and dead patients. We found that the dead patients significantly had higher total leucocyte count, serum creatinine, and MELD score (p 0.001, 0.049, and 0.002, respectively), as well as lower serum albumin (p = 0.028) as illustrated in table 5 and figures 2A-D. Additionally, the ROC curve was applied to identify the sensitivity of each in predicting operative outcome. AUC for total leucocyte count, serum creatinine, MELD score and serum albumin was 0.958, 0.759, 0.963, and 0.765 respectively at cut off >11.5, >1.2, ≤2.3, and >15 respectively (table 6 and figure 3E).
Table (1): Demographic data and clinical characteristics (history and examination) of the studied groups.
History and Examination
Cirrhotic group
(n = 117)
Non-Cirrhotic group
(n = 114)
X2
P value
Sex
Male
Female
No.
%
No.
%
71
46
60.7
39.3
66
38
57.9
42.1
0.186
0.666
Comorbidity
Smoking
DM
HTN
52
36
38
44.44
30.77
32.48
50
34
40
43.86
29.82
35.09
2.021
6.034
4.011
0.974
0.814
0.874
History of hepatic encephalopathy
17
14.5
0
0
NA
---
History of GIT bleeding
Hematemesis and/or melena
Bleeding from other sites
12
10
10.3
8.5
0
0
0
0
NA
NA
----
----
Previous Upper GIT endoscopy
Esophageal Varices and or PHG
Gastritis
Peptic Ulcer
29
18
1
24.8
15.4
0.9
0
10
0
0
8.8
0
NA
39.334
NA
----
˂0.001*
----
General examinations
Pallor
Jaundice
Flapping tremors
Cutaneous manifestations
Lower limb edema
17
13
8
40
34
14.5
11.1
6.8
34.2
29.1
5
0
0
0
0
4.4
0
0
0
0
20.14
NA
NA
NA
NA
<0.001*
---
---
----
----
Conscious state
Fully conscious
DCL
110
7
94.0
6
114
0
100
0
3.253
0.933
Local examination Ascites
No ascites
Mild to moderate
Tense
100
14
3
85.4
12.0
2.6
0
0
0
0
NA
NA
---
---
Liver
Hepatomegaly
Average size
Shrunken
63
22
22
53.8
18.8
18.8
2
112
0
1.8
98.2
0
11.542
0.035*
Spleen
Average size
Splenomegaly
Huge spleen
40
74
3
34.2
63.2
2.6
114
0
0
100
0
0
13.742
0.023*
Hernia
Inguinal hernia
Umbilical hernia
11
7
9.4
5.9
17
1
14.90
0.9
5.041
14.312
0.074
0.021*
HTN: Hypertension, DM: diabetes mellitus, DCL: Disturbed conscious level, PHG: Portal hypertensive gastropathy, GIT: gastrointestinal tract, Cutaneous manifestations: including palmar erythema, spider navai, white nails, ecchymosis patches and skin pigmentations. Bleeding from other sites: epistaxis, bleeding gums, X2 chi-squared, test *significant
Table (2): Pre-operative laboratory investigations of the studied groups.
Table (3): Type of preoperative preparation and urgent intraoperative measures and postoperative ICU admission in patients who undergo surgery groups.
Preoperative Preparation
Cirrhotic patients
(n=102)
Non cirrhotic
(n=109)
X2
P value
N
%
N
%
Plasma
41
40.20
0
0.00
NA
---
Blood
30
29.41
10
9.17
14.04
˂0.001*
Platelet
8
7.84
0
0.00
NA
---
ICU
15
14.71
6
5.50
4.98
0.025*
UGI
10
9.80
0
0.00
NA
---
Intraoperative support and post-operative care
Blood
10
9.80
4
3.66
3.12
0.041*
Plasma
6
5.90
0
0.00
NA
----
Platelets
2
1.96
0
0.00
NA
----
Post-operative ICU
28
27.45
9
8.25
6.83
0.004*
ICU: Intensive Care Units UGI: upper gastrointestinal series
Table (4): Post-operative laboratory changes in comparison to pre- operative basic findings of studies groups.
Variables
Cirrhotic Patients group (n=102)
Non- Cirrhotic group (n=109)
Pre
Post
t test
P value
Pre
Post
t test
P value
Mean ±SD
Mean ±SD
Mean ±SD
Mean ±SD
Hb
10.68±1.97
10.54±1.41
0.911
0.365
11.54±1.61
10.98±1.14
5.860
<0.001*
TLC
7.98±3.05
8.66±2.63
3.015
0.003*
6.94±1.75
8.17±2.12
6.646
<0.001*
PLT
163.82±69.34
165.98±70.15
0.674
0.502
230.39±44.27
250 ±30.5
5.572
<0.001*
Serum albumin
3.10±0.69
2.41±0.38
10.453
<0.001*
4.35±0.54
4.25±0.41
0.841
0.091
Total Bilirubin
1.56±0.68
1.59±1.04
0.317
0.752
0.97±0.13
1.12±0.55
1.018
0.070
INR
1.28±0.249
1.22±0.16
3.159
0.002*
1.05±0.09
1.05±0.11
0.220
0.827
Blood Urea
25.65±11.51
31.77±18.62
3.325
0.001*
14.83±3.35
14.67±4.58
0.306
0.760
Serum Creatinine
1.04±0.29
1.09±0.25
3.502
0.001*
0.93±0.16
1.08±1.25
1.231
0.221
ALT
54.81±50.33
50.85±34.64
0.637
0.525
31±49.37
34.5±54.63
0.413
0.066
AST
73.29±68.01
65.76±47.63
0.928
0.356
45±61.24
54±64.25
0.891
0.052
Serum Na
135.66±4.37
134.69±3.92
3.552
0.001*
138.34±2.49
134.84±12.78
2.920
0.004*
Serum K
3.84±0.48
3.74±0.61
1.377
0.172
4.29±0.55
5.33±12.54
0.858
0.393
Hb: hemoglobin, TLC: total leucocyte count, AST: aspartate aminotransferase, INR: international normalized ratio, PLT: platelets, ALT: Alanine transaminase, Paired t test used to compare laboratory investigations pre and post operation among patients and control group t: independent t test *significant
S. Table (4): Intraoperative measures and postoperative ICU admission in patients undergoing surgery regarding operation urgency type.
Intraoperative support
Cirrhotic group (n=102)
X2
P
value
Non-Cirrhotic group (n=109)
X2
P
value
Elective (n=82)
Emergency (n=20)
Elective (n=97)
Emergency (n=12)
No. (%)
No. (%)
No. (%)
No. (%)
Blood
6 (7.32)
4 (20.0)
1.621
0.514
3 (3.09)
1 (8.33)
0.331
0.063
Plasma
3 (3.66)
3 (15.0)
1.234
0.632
0 (0.0)
0 (0.0)
NA
----
Platelets
0 (0.0)
2 (10.0)
NA
----
0 (0.0)
0 (0.0)
NA
----
Post-operative ICU
14(17.0)
14(70.0)
4.67
0.012*
4 (4.12)
5 (41.67)
7.83
0.003*
:
ICU: Intensive Care Unit X2chi -squared test *significant
Table (5): Comparison between survived and died patients regarding preoperative data in cirrhotic group.
Mortality
Test value
P-value
Negative
Positive
No. = 98
No. = 4
Age
Mean ± SD
53.01 ± 8.92
60.75 ± 9.36
-1.699
0.092
Range
36 – 70
50 – 70
Hb
Mean ± SD
10.74 ± 1.98
8.98 ± 0.41
1.779
0.078
Range
4.9 – 14
8.5 – 9.5
TLC
Mean ± SD
7.74 ± 2.86
13.75 ± 1.50
-4.162
< 0.001*
Range
2.7 – 15
12 – 15
PLT
Mean ± SD
164.27 ± 70.61
153.00 ± 22.54
0.317
0.752
Range
42 – 295
124 – 178
Blood urea
Mean ± SD
25.48 ± 11.58
29.75 ± 9.74
-0.726
0.470
Range
10 – 65
18 – 40
Serum creatinine
Mean ± SD
1.03 ± 0.29
1.33 ± 0.29
-1.994
0.049*
Range
0.5 – 1.7
1 – 1.7
Alb
Mean ± SD
3.15 ± 0.68
2.08 ± 0.22
3.145
0.002*
Range
2 – 4
1.8 – 2.3
INR
Mean ± SD
1.27 ± 0.24
1.50 ± 0.37
-1.818
0.072
Range
0.9 – 2
1 – 1.9
ALT
Median (IQR)
37 (22 - 70)
31 (21 - 40)
-0.837
0.403
Range
10 – 305
20 – 40
AST
Median (IQR)
61 (28 - 98)
34.5 (19 - 45)
-1.492
0.136
Range
8 – 398
14 – 45
Child grade
Child A
47 (48.0%)
0 (0.0%)
3.678
0.159
Child B
41 (41.8%)
3 (75.0%)
Child C
10 (10.2%)
1 (25.0%)
MELD score
Mean ± SD
11.30 ± 3.64
15.50 ± 5.20
-2.232
0.028*
Range
6 – 20
8 – 19
*: Chi-square test; •: Independent t-test; ‡: Mann Whitney test
Table (6): Validity (AUC, sensitivity, specificity) of some parameters (TLC, serum creatinine, serum albumin and MELD score) to discriminate between different groups.
Parameter
AUC
Cut of Point
Sensitivity
Specificity
PPV
NPV
TLC
0.958
>11.5
100.0
89.8
28.6
100.0
Serum Creatinine
0.759
>1.2
75.0
74.49
10.7
98.6
Serum albumin
0.963
≤2.3
100.0
86.73
23.5
100.0
MELD score
0.765
>15
75.0
85.71
17.6
98.8
TLC: total leucocyte count
DISCUSSION
Cirrhosis is caused by various liver injury mechanisms that result in necro-inflammation and fibrogenesis. Histologically, it is identified by diffuse nodular regeneration surrounded by dense fibrotic septa which significantly distorts the hepatic vascular architecture. This results in portal hypertension and in hepatic synthetic dysfunction. Clinically, cirrhosis has been considered an end-stage disease that results in death, unless liver transplantation is done, the only prophylactic measures have been esophageal varices screenings and hepatocellular carcinoma screenings [11].
As the incidence of CLD and cirrhosis increases, more cirrhosis patients are undergoing surgery of various kinds. It is generally known that after surgery, individuals with underlying CLD experience higher rates of morbidity and mortality than those without. Surgery-related and anesthesia-related problems are more likely to occur in patients with liver disease than in those with a healthy liver [12]. There are a number of factors that contribute to poor outcomes in patients with advanced liver disease after surgery, including the fact that cirrhosis is linked to an increased output and hyperdynamic circulation, as well as a decreased hepatic perfusion that may be vulnerable to hypoxemia and hypotension related to the anesthesia [13].
Cirrhosis has 2 distinct phases: compensated and decompensated. The decompensated state of cirrhosis is characterized by the presence of its consequences, including variceal bleeding, HE, ascites, SBP, HCC, hepatopulmonary syndrome (HPS), and hepatorenal syndrome (HRS), characterizes the decompensated state of the cirrhosis [11]. Patients with impaired liver function are known to experience decompensatory effects from anesthesia and surgery.
In spite of being known that general anesthesia reduces the arterial blood flow to liver and increases the risk of ischemic injury, spinal or epidural anesthesia may also lower mean arterial pressure, which is problematic in cirrhotic patients who already have hyperdynamic circulation as a result of peripheral vasodilatation. As coagulopathy or thrombocytopenia is present, these approaches are not preferred because of the increased risk of bleeding. Consequently, for these patients, general anesthesia may represent the preferred option [14].
In our study, we aimed to assess the surgical risk for patients with liver cirrhosis and to identify numerous variables that would influence how successfully these patients would respond to surgery. 231 participants underwent non hepatic surgery under general anesthesia. 231 individuals in this study underwent non-hepatic surgery while under general anesthesia. Their preoperative assessment of their readiness for surgery, as well as the intra operative outcome after surgery were all part of their workup.
In this work we noticed that only 12.8% of the cirrhotic patients who had surgery had a Child Pugh score of C, making the majority of them either Child Pugh score A or B, representing 42.7% and 44.5% respectively. These results were in line with those of del Olmo and his colleagues, in their study on non-hepatic surgery on 135 cirrhotic patients, reported that the degree of liver dysfunction before operation was evaluated as Child-Pugh grade A in 83 patients, B in 41 patients, and C in 11 patients [15].
Although there were statistically non-significant differences between the cirrhotic and non-cirrhotic groups in the current study for patients who had or had not undergone surgery (p>0.05), there was nevertheless a trend for cirrhotic patients to be non-operated. We found that hepatic causes predominate in Child B and C, whereas non-hepatic causes predominate in patients with Child A cirrhosis.
Comparing the preoperative preparation of cirrhotic and non-cirrhotic patients, the current study found that 40.20% of the cirrhotic group required plasma transfusion and 7.84% required platelet transfusion, while, none of the non-cirrhotic group did. According to Keegan and Plevak, coagulopathy and thrombocytopenia should be treated with vitamin K replenishment, fresh-frozen plasma (FFP) administration, and possibly cryoprecipitate transfusions in order to reduce prothrombin times to within 3 seconds of normal values platelet counts should be greater than 50,000/mm3[16].
Additionally, this study also revealed that only cirrhotic patients required intra-operative plasma and platelet transfusion, and that there was a statistically significant difference between the cirrhotic and non-cirrhotic groups in terms of the need for post-operative ICU admission and intra-operative blood transfusions.
Cirrhotic patients' hemostasis changes are complex. Cirrhosis impacts procoagulant and anticoagulant levels [17]. Further complicating the matter is the lack of routine diagnostics to determine how cirrhosis affects anticoagulant levels. Because of this, assessing the impact on procoagulants only and showing a higher INR in a patient with cirrhosis do not indicate an increased risk of bleeding in these patients. However, use of INR is still a frequent practice in the absence of a suitable test to assess changes in hemostasis in patients with cirrhosis [14].
A cutting- novel technique called thromboelastography evaluates all the stages of clot lysis and formation. When accessible, it should be used since it assesses the blood clotting process' viscoelastic characteristics. It can accurately determine which blood product should be used based on the lack of various components involved in the formation of blood clots [18]. It has been demonstrated to lower the procedure's need for unnecessary transfusions and the complications that go along with it without raising bleeding complications. Fresh frozen plasma (FFP) is frequently utilized to reduce increased INR when thromboelastography is not available [19].
Furthermore, thrombocytopenia is typical in cirrhotic patients. The suggested mechanisms include enhanced destruction by hypersplenism and decreased thrombopoietin synthesis, which stimulates the production of platelets in the bone marrow. If the platelet count is less than 50000/mm3, a prophylactic platelet transfusion is recommended before surgery [20].
Additionally, cirrhotic patients received pre-operative care that included nutritional supplementation, hepatic encephalopathy management, and ascites correction. We noticed that optimal management of ascites reduced certain postoperative complications such as recurrence of an umbilical hernia. Similarly, Abbas et al. have cautioned that surgical procedures that were previously prohibited due to ascites may become achievable in some cirrhotic patients and that pharmacological management of ascites may improve the CTP class [14].
We paid close attention to any preexisting infections during the preoperative assessment and appropriately treated them. According to a previous study, Douard et al. found that cirrhotic patients with undetected and untreated infections had higher rates of morbidity and mortality following the same surgery than non-cirrhotic patients [21].
In this study, post-operative mean values of TLC, blood urea, and serum creatinine were significantly higher than pre-operative mean values, whereas post-operative mean values of serum albumin and serum Na were significantly lower, however, no significant changes were noted regarding liver functions in non-cirrhotic group. In accordance with the findings of Ziser et al. According to their findings, 20% of cirrhotic patients had worsening hepatic functions, and some of them experienced decompensation of liver cirrhosis that was not evident prior to surgery [22].
In the current study, we noticed a substantial difference between patients who received elective and emergency surgeries in the cirrhotic group, with elective surgeries showing more frequent complications and only emergency surgeries revealing post-operative death. Only emergency procedures were linked to post-operative mortality in non-cirrhotic patients, however, where there was a statistically non-significant difference between elective and emergency operations regarding post-operative morbidity. Prior research has shown that patients with cirrhosis who require emergency surgery have a higher risk of morbidity and mortality unless they receive the appropriate preoperative management and care [23].
Regarding the Child-Turcotte-Pugh grading, we observed a non-significant difference between survived dead and dead patients, However, dead patients only belonged to Child Pugh Grades B or C. Earlier analyses have shown less of an association between the Child-Pugh class and surgical outcomes [24]. Perhaps this is attributed to the small number of patients with Child-Pugh class C cirrhosis who were included in trials to avoid surgery in patients with decompensated cirrhosis and prefer conservative therapy whenever possible.
In the current study, patients who survived and those who died were compared based on preoperative data from the cirrhotic group. We noticed that the dead patient had a significantly higher serum creatinine, total leucocyte count, and MELD score together with a considerable lower serum albumin. This is closely similar to previous studies that have reported that the MELD score has largely replaced the use of the CTP score for surgical risk stratification due to the somewhat subjective nature of estimating the severity of ascites and encephalopathy. The MELD score incorporates the objective liver function-dependent components of the CTP score which have been found to be predictive of outcomes [25, 26].
CONCLUSION
Hepatic and non-hepatic complications are common in cirrhotic patients including decompensation. Cirrhotic patients had considerable higher morbidity and mortality rates than controls, in both groups emergent operations are associated with undesirable outcomes. Cirrhotic patients need distinctive perioperative care. Optimal perioperative care could decease such complications. Correction of coagulopathy, care for preexisting encephalopathy, management of ascites, avoidance of sepsis, and optimizing kidney function should all be part of preoperative preparation.
Abbreviations
ALT: Alanine transaminase, AST: Aspartate aminotransferase, CTP; Child-Turcotte-Pugh, HBV: Hepatitis B virus, HCV: Hepatitis C virus, INR: International normalized ratio, MELD: Model for End-Stage Liver Disease, SBP: Spontaneous bacterial peritonitis,
Disclosure
Ethics approval and consent to participate
Before being enrolled in this study, all participants were given a description of the study and given the opportunity to give their informed consent. The study was carried out after approval from the ethical committee, Faculty of Medicine, Menoufia University and per the Declaration of Helsinki.
Consent for publication
Not applicable.
Availability of data and material
All data generated or analyzed during this study are included in this published article.
Competing interests
The authors declare that they have no competing interests.
Funding
The study was fully non-funded from any organization.
Authors' contributions
All authors contributed significantly to the work reported, whether it be in the ideation, study design, implementation, data collection, analysis, and interpretation, or in all of these areas. They also participated in writing, revising, or critically evaluating the article, gave their final approval for the version to be published, decided on the journal to which the article has been submitted, and agreed to be responsible for all aspects of the work.
Acknowledgements
Not applicable.
References
Hadjihambi A, Arias N, Sheikh M, Jalan R. Hepatic encephalopathy: a critical current review. Hepatol Int. 2018 Feb; 12(Suppl 1):135-147. doi: 10.1007/s12072-017-9812-3. Epub 2017 Aug 2. PMID: 28770516; PMCID: PMC5830466.
Murray CJ, Vos T, Lozano R. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380:2197–2223.
Elsharkawy A, El-Raziky M, El-Akel W, El-Saeed K, Eletreby R, Hassany M, et al. Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience. J Hepatol. 2018 Apr; 68(4):691-698. doi: 10.1016/j.jhep.2017.11.034. Epub 2017 Dec 6. PMID: 29223371.
Northup PG, Friedman LS, Kamath PS. AGA Clinical Practice Update on Surgical Risk Assessment and Perioperative Management in Cirrhosis: Expert Review. Clin Gastroenterol Hepatol. 2019 Mar; 17(4):595-606. doi: 10.1016/j.cgh.2018.09.043. Epub 2018 Sep 28. PMID: 30273751.
Gasteiger L, Eschertzhuber S, Tiefenthaler W. Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure. Eur Surg. 2018; 50(3):81-86. doi: 10.1007/s10353-018-0522-4. Epub 2018 Apr 13. PMID: 29875796; PMCID: PMC5968074.
Sarmast N, Ogola GO, Kouznetsova M, Leise MD, Bahirwani R, Maiwall R, et al. Model for End-Stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease. Hepatology. 2020 Nov; 72(5):1747-1757. doi: 10.1002/hep.31199. PMID: 32083761.
Acharya G, Kaushik RM, Gupta R, Kaushik R. Child-Turcotte-Pugh Score, MELD Score and MELD-Na Score as Predictors of Short-Term Mortality among Patients with End-Stage Liver Disease in Northern India. Inflamm Intest Dis. 2020 Feb; 5(1):1-10. doi: 10.1159/000503921. Epub 2019 Nov 8. PMID: 32232049; PMCID: PMC7098314.
Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646-9. doi: 10.1002/bjs.1800600817. PMID: 4541913.
Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001 Feb;33(2):464-70. doi: 10.1053/jhep.2001.22172. PMID: 11172350.
Columbus AB, Morris MA, Lilley EJ, Harlow AF, Haider AH, Salim A, et al. Critical differences between elective and emergency surgery: identifying domains for quality improvement in emergency general surgery. Surgery. 2018 Apr; 163(4):832-838. doi: 10.1016/j.surg.2017.11.017. Epub 2018 Jan 10. PMID: 29331398.
D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan;44(1):217-31. doi: 10.1016/j.jhep.2005.10.013. Epub 2005 Nov 9. PMID: 16298014.
Northup PG, Friedman LS, Kamath PS. AGA Clinical Practice Update on Surgical Risk Assessment and Perioperative Management in Cirrhosis: Expert Review. Clin Gastroenterol Hepatol. 2019 Mar;17(4):595-606. doi: 10.1016/j.cgh.2018.09.043. Epub 2018 Sep 28. PMID: 30273751.
Filmann N, Walter D, Schadde E, Bruns C, Keck T, Lang H, et al. Mortality after liver surgery in Germany. Br J Surg. 2019 Oct;106(11):1523-1529. doi: 10.1002/bjs.11236. Epub 2019 Jul 24. PMID: 31339558.
Abbas N, Makker J, Abbas H, Balar B. Perioperative Care of Patients With Liver Cirrhosis: A Review. Health Serv Insights. 2017 Feb 24; 10:1178632917691270. doi: 10.1177/1178632917691270. PMID: 28469455; PMCID: PMC5398291.
del Olmo JA, Flor-Lorente B, Flor-Civera B, Rodriguez F, Serra MA, Escudero A, et al. Risk factors for nonhepatic surgery in patients with cirrhosis. World J Surg. 2003 Jun; 27(6):647-52. doi: 10.1007/s00268-003-6794-1. Epub 2003 May 13. PMID: 12732995.
Keegan MT, Plevak DJ. Preoperative assessment of the patient with liver disease. Am J Gastroenterol. 2005 Sep; 100(9):2116-27. doi: 10.1111/j.1572-0241.2005.41453.x. PMID: 16128958.
Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction? J Hepatol. 2011 Dec; 55(6):1415-27. doi: 10.1016/j.jhep.2011.06.008. Epub 2011 Jun 28. PMID: 21718668.
De Pietri L, Bianchini M, Montalti R, De Maria N, Di Maira T, Begliomini B, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial. Hepatology. 2016 Feb; 63(2):566-73. doi: 10.1002/hep.28148. Epub 2015 Dec 9. PMID: 26340411.
Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008 Jun; 48(6):1000-7. doi: 10.1016/j.jhep.2008.03.009. Epub 2008 Mar 31. PMID: 18433919.
Douard R, Lentschener C, Ozier Y, Dousset B. Operative risks of digestive surgery in cirrhotic patients. Gastroenterol Clin Biol. 2009 Jun-Jul;33(6-7):555-64. doi: 10.1016/j.gcb.2009.03.012. Epub 2009 May 29. PMID: 19481892.
Ziser A, Plevak DJ. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Curr Opin Anaesthesiol. 2001 Dec; 14(6):707-11. doi: 10.1097/00001503-200112000-00018. PMID: 17019169.
Bhangui P, Laurent A, Amathieu R, Azoulay D. Assessment of risk for non-hepatic surgery in cirrhotic patients. J Hepatol. 2012 Oct; 57(4):874-84. doi: 10.1016/j.jhep.2012.03.037. Epub 2012 May 23. PMID: 22634123.
Telem DA, Schiano T, Goldstone R, Han DK, Buch KE, Chin EH et al. Factors that predict outcome of abdominal operations in patients with advanced cirrhosis. Clin Gastroenterol Hepatol 2010; 8:451–457, quiz e458.
Befeler AS, Palmer DE, Hoffman M, Longo W, Solomon H, Di Bisceglie AM. The Safety of Intra-abdominal Surgery in Patients With Cirrhosis: Model for End-Stage Liver Disease Score Is Superior to Child-Turcotte-Pugh Classification in Predicting Outcome. Arch Surg. 2005; 140(7):650–654. doi:10.1001/archsurg. 140.7.650
Northup PG, Friedman LS, Kamath PS. AGA Clinical Practice Update on Surgical Risk Assessment and Perioperative Management in Cirrhosis: Expert Review. Clin Gastroenterol Hepatol. 2019 Mar; 17(4):595-606. doi: 10.1016/j.cgh.2018.09.043. Epub 2018 Sep 28. PMID: 30273751.