Factor Predicting Cholestasis in Post Modified Right Lobe Hepatectomy in the Era of Standardized Donor Selection Protocols

Donor Evaluation

All live donor applied for live donation voluntarily without any financial benefit. Donors age more than 18 and less than 60 years was considered as fit for donation. Identical blood group was preferred but incompatible group also accepted. No physical or mental morbidity, which might impact the tolerance and awareness of the procedure, should be found in donors.

Donor work up was proceeded as per Our Evaluation Algorithm for Selecting Living Donor Candidate for LT as shown in Table 1. After completion of blood work up we proceeded for 3 tesla MRI done to visualise the biliary anatomy and fat assessment was also done by Proton density fat fraction technique. When the fat was more than 17 % on imaging, we did a liver biopsy. If biopsy shows more than 30 % then they are placed on weight loss protocol until there was correction of fat fraction on imaging. CECT Computed Tomography (CT) scan done with 126 slicer CT Philips system with timings of Vascular Anatomy was assessed along with Remnant Assessment (GE, Vicar software). At least 30% including caudate lobe with MHV for volumetric measurement was performed to evaluate graft size and the size of remnant donor liver. Remnant volume of < 30% of the whole liver volume was regarded as optimal safety margin for donors.

Step 1

Haematology

Blood Grouping

Complete Blood Count

PT, PTTK

Biochemistry

Liver Function Tests

Operative Techniques

A Makuchi incision was routinely applied. Liver remnant was reassessed by senior surgeons.

Intraoperative cholangiogram (IOC) was done to reconfirm the biliary anatomy. Then portal pressure (PP) and Middle Hepatic Vein (MHV) congestion measurement are done. If PP more than 3 then it was contraindication for modified right lobe, surgical technique is modified or else the donor operation is abandoned. If no abnormality was found, the surgery was continued by parenchyma transection with Cavitron Ultrasonic Suction and Aspirator (CUSA). The transaction line was determined by hepatic vascular occlusion. Veins (>5mm) were temporarily clippedwith titanium clip and were used for further reconstruction in the recipient. After total dissociation of the right lobe, the right hepatic artery, right portal trunk, and right hepatic vein were interdicted and transected in an orderly manner. Heparinisation was done before ligating the hepatic veins, the haemorrhage and bile leakage were paired with 5–0 prolene and 6–0 PDS (polydioxanone), respectively, over the transected surface. IOC was repeated to assess the remaining biliary system at the end of the operation. The weight of the graft was measured at the back table and documented into our database. Intra-peritoneal sub-hepatic tube was placed in all cases.

Postoperative Treatment and Follow-up

All donors were extubated on table. Arterial blood gas (ABG) analysis was done as lactate is a good marker of patient recovery. Donors were transferred to Intensive Care Unit (ICU) for liver transplantation right after the procedure. ABG was done 4 hourly. Intravenous antibiotics, Proton pump inhibitors, intravenous analgesics were given and continued until POD2. Liver doppler was done on POD 1. Once donors were stable, they were moved to clinical ward (CW). Intra peritoneal sub-hepatic drains were removed on POD4 once drain output was low and sero hemorrahgic. Donors were given abdominal belt for two weeks. The total hospital Length of Stay (LOS) was calculated as time admitted to the ICU to the time of discharge. All the donors were discharged with normalised Tbil and INR, with healthy wound and normal lifestyle. They were prescribed oral analgesics to if required and was called for follow up after 3 days. At outpatient department they were advised for basic Complete blood count, Liver function test, Kidney function to see the general wellbeing. After that they were not called for follow up until they had any problems.

Statistical Analysis

Follow up was continued until October 2019.To identify risk factor for cholestasis of donors variables concerning living donors were assessed by univariate analyses using the chi-square test or Fisher’s exact test where appropriate were performed to compare categorical variables, and the Wilcoxon rank sum test was used to compare continuous variables. A logistic model was applied for estimation of odds ratio (OR) associated with post-operative donor cholestasis. Statistical analyses were performed using JMP statistical software, version Genomics 13 (SAS Institute, Cary, NC). All P values presented are two-sided. P values of<0.05 were considered statistically significant.

Demographics and Operative Variables of the Living Liver Donors

Donor demographics and operative variables were analysed (data not shown). Of 386 donors, 178 (46.11 %) were females and 208 (53.88 %) were males. The mean age was 33.04 years and mean BMI was 25.5. The mean LAI was 8.34 and mean ± SD right lobe volume without MHV was 831.86 ± 168.72. The mean remnant percent was 35.7 %. Intraoperative parameters were as the mean congestion area was 38.8 % with mean actual graft weight 781.2 ± 142.3 gm.

Postoperative Cholestasis

We further looked for risk factors for cholestasis. Risk factors were analysed based on two cut off values of Tbil as mentioned above. On analysis the median Peak Bilirubin was 2.3mg/dL. Of the 286 living donors, 185 had more than 2.3 mg/dL peak bilirubin. We analysed several perioperative variables to find out the risk factors for donor cholestasis in between the two groups. Further we also divided cholestasis group with the cut of peak Tbil as 5 mg/dL. Of the 386 living donors, 19 had Tbil more than 5 mg/dL.

Risk Factors for Post MRL Hepatectomy Cholestasis

We analysed several risk factors for development of cholestasis in both groups. When we took the Tbil cut off as 2.3 mg/dL, on univariate analysis we found that male gender had higher chance of developing cholestasis (45.27 % vs 63.24 %, P value= 0.0004), and less remnant % (36.38 ± 4.76 vs 34.96 ± 4.55, P value= 0.001), was found to be significant risk factors (Table 2). Similarly, when we compared the variables with the cut off as 5 mg/dL, male gender (52.59 % vs 78.95%, P value= 0.024), Blood group O (51.5 % vs 78.95 %, P value= 0.019), less BMI (25.69 ± 4.59 vs 23.14 ± 2.45, P value= 0.005) were significant risk factors between 2 groups. (Table 3).

Table 2: Characteristics and Perioperative Data of MLR Donors with Tbil cut off >2.3. Categorical variable are presented as number (%) while continuous variable are presented as mean±SD*. Pearson chi-square test/ Wilcoxon test ,A difference was considered significant if p-value was < 0.05. BMI, body mass index, LAI, liver attenuation index, MPV, main portal vein, RPV, right portal vein, LPV, left portal vein, RHV, right hepatic vein, CPP, corrected portal pressure, INR, international normalization ratio, Tbil, Total bilirubin, POD, post-operative day.

Risk Factors on Multivariate Analysis

The multivariate logistic regression analysis identified one independent factor that is male gender that contributed significantly to the differences between patients with and without cholestasis when the the cut of Tbil was 2.3 mg% (OR 2.14 [confidence interval (CI): 1.23–2.73], p= 0.006 respectively) (Table 4). Similarly when we took the Tbil cut off as 5 mg%, we found out that blood group O (OR 4.9, (CI): 1.26- 19.8, p= 0.02) and again male gender (OR 0.85, (CI): 0.76- 0.97, p= 0.01) (Table 5) was significant contributory for development of major cholestasis after MRL in healthy donor.