Eung-Ho Cho

Three‐quarters of right liver donors experienced postoperative complications

A donor right hepatectomy (RH) is associated with a higher rate of morbidity than a left hepatectomy. Therefore, the precise morbidity should be known to improve the success of donor RH implementation. However, the rate of complication varies according to the individual definition of morbidity. This study prospectively analyzed the outcomes of 83 consecutive living donor RHs between January 2002 and July 2004 using a standardized classification of the severity of complications. The morbidity was classified using the modified Clavien system: grade I for minor complications; grade II for potentially life‐threatening complications requiring pharmacological treatment; grade III for complications requiring invasive intervention; grade IV for complications causing organ dysfunction requiring intensive care unit management; and grade V complications resulting in the death of the patient. The donors were followed‐up regularly for at least 12 months. No donor death or relaparotomy was noted. Overall, 65 out of 83 donors (78.3%) experienced postoperative complications: grades I, II, III, IV, and V complications in 64 (77.1%), 11 (13.3%), 1 (1.2%), 0, and 0 patients, respectively. The most common grade I complications were hyperbilirubinemia (n = 31) and pleural effusion (n = 31), and bile leakage in grade II (n = 7). The bilirubin and alanine aminotransferase levels were normal in 92.7% of donors at the 1‐year follow‐up. In conclusion, although most of these adverse events were minor and self‐limited, 78% of right liver donors still experienced morbidity. Therefore, continuous standardized reporting of the donor morbidity as well as meticulous surgery and intensive care are essential for the success of donor RH implementation. Liver Transpl 13:797–806, 2007.

An artificial vascular graft is a useful interpositional material for drainage of the right anterior section in living donor liver transplantation

Congestion in the anterior section in a right liver (RL) without a middle hepatic vein (MHV) may lead to graft dysfunction. To solve this problem, an RL draining MHV branches with autologous or cryopreserved vessels can be introduced. However, these vessels are often unavailable, and their preparation is time‐consuming. An expanded polytetrafluoroethylene (ePTFE) graft may be used for anterior section drainage. Between February and November 2005, 26 recipients underwent RL liver transplantation draining MHV branches with an ePTFE graft (group P). Twenty‐six ePTFE grafts (6 or 7 mm in internal diameter) drained 35 MHV branches on the back table to the graft right hepatic vein or to the recipients inferior vena cava. The patency of the ePTFE graft was checked with computed tomography scans of the liver. The outcome of group P was compared with those of an RL group with MHV (group M, n = 17) and an RL group without reconstruction of MHV or its tributaries (group R, n = 85). The 1‐month and 4‐month patency rates (PRs) of the ePTFE grafts were 80.8% (21/26) and 38.5% (10/26). All showing early obstruction of the ePTFE graft had congestion in the anterior section, but all showing late obstruction were asymptomatic. The 1‐month PRs of group P were comparable to, but the 4‐month PRs were lower than, those of group M (both 94.1%; P < 0.05). However, 1‐year patient and graft survival rates of group P (both 100%) were comparable to those of group M (94.1% and 100%) and better than those of group R (83.5% and 88.2%; P < 0.05). In conclusion, the early PR of group P was good, and late obstruction of the ePTFE graft had no impact on congestion in the anterior section or patient survival. Therefore, an ePTFE graft may be a useful interposition material for anterior section drainage in RL transplantation without serious complications. Liver Transpl 13:1159–1167, 2007.

Classification and prognosis of intrahepatic biliary stricture after liver transplantation.

Intrahepatic biliary stricture (IHBS) after liver transplantation (LT) may develop in patients with hepatic artery thrombosis, chronic rejection, or ABO incompatibility, as well as in patients with prolonged warm ischemia in non‐heart‐beating donor (NHBD) LT. However, the clinical course and methods of management have not been well defined for IHBSs to date. Thus, the purpose of this study was to provide a classification of post‐LT IHBS and to investigate patient prognosis. Forty‐four patients who developed IHBS after NHBD LT were enrolled. On the basis of the cholangiographic appearance, patients were classified into 4 groups: unilateral focal (UF, n = 8), confluence (CO, n = 10), bilateral multifocal (BM, n = 21), and diffuse necrosis (DN, n = 5). The UF type was defined as cases with stricture only in the segmental branch of the unilateral hemiliver; the CO type in cases with several strictures at confluence level; and the BM type in cases with multiple strictures bilaterally. Cases with diffuse obliteration of peripheral ducts or destruction of the central architectural integrity, over a long segment, were classified as the DN type. Five patients with the CO type required several interventions requiring biliary dilatation, yet all patients with the UF or CO type had a good prognosis. Among the patients with the BM type, 3 patients (14.3%) died or underwent retransplantation due to biliary complications, and 7 (33.3%) required repeated interventions for >1 year without improvement. Moreover, among 5 patients classified as the DN type, 1 (20%) died of biliary sepsis, 2 (40%) underwent retransplantation, and the remaining 2 (40%) did not recover from persistent jaundice and life‐threatening cholangitis despite multiple interventions. In conclusion, all patients classified as UF or CO had a good outcome with or without additional interventions. However, all patients with the DN type and about half the patients with the BM type did not recover from life‐threatening complications, despite repeated aggressive interventions; early retransplantation was therefore the only treatment option for these patients. Liver Transpl 13:1736–1742, 2007.

Outcomes of hepatic resection for a single large hepatocellular carcinoma

BackgroundThe proper role of surgical resection, given the various treatment modalities available, needs to be further clarified in patients with a single large hepatocellular carcinoma (HCC). To evaluate the role of surgical resection in this group of patients, we studied the long-term outcomes of patients that received hepatic resection for a single large (> 5–10 cm in diameter) HCC.MethodsThe clinicopathologic data and long-term outcomes of 61 patients with a single large HCC (> 5–10 cm in diameter; L group) were compared with those of 169 patients with a single small HCC (≤ 5 cm; S group). Prognostic factors were evaluated by univariate and multivariate analysis.ResultsOperative mortality rates were low in both groups (0.6% in group S and 1.6% in group L), and the incidence of postoperative hepatic failure was rare even in group L (1.6%). The cumulative 5-year overall survival rate in group S was 59.0%, whereas in group L it was 52.9% (p = 0.385), and the corresponding cumulative 5-year disease-free survival rates were 44.1% and 31.7%, respectively (p = 0.063). Child class B was found to predict poor overall and disease-free survival by multivariate analysis versus Child class A in both groups. The presence of microvascular invasion was also identified as a significant prognostic factor, but it only affected disease-free survival in the two groups.ConclusionsSingle large HCCs do not require a large extent of hepatic resection and the associated increased risk of postoperative liver failure. The long-term survival of patients with a single large HCC is as good as that of patients with a single small HCC. We conclude that hepatic resection is a safe and effective therapy for single large HCCs.

Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria.

Background: To expand the Milan criteria, prognostic factors other than size and number of tumor may be necessary. We analyzed outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) exceeding Milan criteria to select favorable group of patients. Methods: Between November 1997 and December 2005, 104 cases of liver transplantation for patients with HCC were performed at our center. Twenty-four patients did not meet the Milan criteria preoperatively. Among these 24 patients, 19 had no major vascular invasion at the time of surgery. We analyzed the survival and prognostic factors of these 19 patients. The mean follow-up period was 33 months (range 6–89). Results: Three-year survival rate in 19 patients was 67.4%. Three-year survival rates were significantly higher when preoperative alpha-fetoprotein was less than 400 ng/ml (86.2 vs. 0%, p<0.001) when Edmonson-Steiner’s histological grade 1 or 2 (100 vs. 40%, p = 0.036) and when microvascular invasion was absent (78.6 vs. 30%, p = 0.039). Conclusion: If vascular invasion is absent in preoperative radiological studies, and the preoperative alpha-fetoprotein is less than 400 ng/ml, our findings suggest a good prognosis after liver transplantation for HCC patients who do not meet the Milan criteria.

Hepatic steatosis is associated with intrahepatic cholestasis and transient hyperbilirubinemia during regeneration after living donor liver transplantation

A clear understanding of the mechanisms in steatotic livers that trigger cholestasis or hyperbilirubinemia after living donor liver transplantation (LDLT) remains elusive. We hypothesized that microarchitectural disturbance might occur within regenerating steatotic livers without impairment of hepatic proliferative activity. Liver biopsy specimens from 67 LDLT recipients taken at the 10th postoperative day were scored for the numbers of portal tracts per area (nPT/A) of liver tissue and for intrahepatic cholestasis, and immunostained by proliferating cell nuclear antigen (PCNA) and Ki‐67. The preoperative degree of macrovesicular steatosis (MaS) was independently associated with cholestasis after LDLT (P < 0.001). Serum total bilirubin results on the 1st, 3rd, and 7th days post‐LDLT in MaS+ (5–30% of MaS; n = 37) patients were significantly higher than those in MaS− (<5% of MaS; n = 30) patients (P = 0.030, 0.042, and 0.019, respectively). Mean numbers of positively stained hepatocytes were 53.1 ± 12.0 in patients with MaS and 48.0 ± 17.1 in those without MaS by PCNA (P = 0.390), and 24.4 ± 10.5 and 24.0 ± 14.0 by Ki‐67 (P = 0.940). However, a significant negative correlation was found between the degree of MaS and nPT/A (P = 0.013), and nPT/A was correlated with the grade of histological cholestasis (r = 0.350, P = 0.039). Intrahepatic cholestasis and hyperbilirubinemia after LDLT could be caused by scanty morphologic change of portal tract during steatotic liver regeneration.

Safety of modified extended right hepatectomy in living liver donors

In living donor liver transplantation (LDLT), the standard right graft has been adopted by many centers to meet the metabolic demands of large recipients. In conventional right liver graft, congestion at anterior section may be problematic especially when graft volume is insufficient. We previously introduced a technical aspect of modified extended right hepatectomy (MERH), in which the middle hepatic vein was excavated by preserving the entire segment 4 (Sg4) to the donor. In this report, we investigated the safety of donors who received MERH. Between August 2002 and July 2005, 97 donors underwent right liver donation. MERH was considered when remnant‐left liver volume exceeded 35% of whole liver. Eighteen donors underwent MERH (MERH group, n =18). We compared the clinical outcomes of MERH group with those of donors who underwent conventional right hepatectomy (RH) with remnant liver volume exceeding 35% (RH group, n = 37). No donor mortality occurred. No intra‐operative transfusion and no re‐operation were performed. There were no differences in operative time (290.8 min in MERH group vs. 297.0 min in RH group, respectively), blood loss (453.3 ml vs. 426.5 ml), and postoperative hospital stay (12.5 days vs. 12.8 days) between the two groups (P > 0.05). Period of drain removal was longer in MERH group (12.5 days vs. 9.4 days, P < 0.05). But, there was no difference in complication rate between the two groups (11/18 vs. 23/37, P > 0.05). Computed tomography scan showed that congestion of Sg4 was occurred in 13 out of 18 MERH donors in early postoperative period, but all recovered at 4 months. The regeneration of the remnant liver after MERH and RH were similar (209.8% vs. 200.0% at 4 months, P > 0.05). Our results show that MERH did not impair recovery or liver regeneration in donors, and indicate that MERH can be safely done in adult LDLT when the remnant liver exceeds 35%.

Hypoattenuation in unenhanced CT reflects histological graft dysfunction and predicts 1-year mortality after living donor liver transplantation

Early postoperative graft function assessments are essential after living donor liver transplantation (LDLT) to predict patient and graft outcome. Computed tomography (CT) is usually used to evaluate various complications and parenchymal abnormalities after LDLT. Here, we attempted to determine the prognostic values of CT attenuation changes of grafts for predicting 1‐year patient survival. Liver attenuation indices (LAIs), derived from differences between hepatic and splenic attenuations, were calculated on unenhanced CT images obtained 10 days after LDLT in 62 adult LDLT recipients between September 2002 and August 2004. Patients were assigned to 1 of 2 groups according to LAI value on the 10th postoperative day, as follows: group L (LAI ≤ 5, n = 14) or group H (LAI > 5, n = 48). Parenchymal dysfunction scores, summed parameters for histological dysfunction including both portal tract and centrilobular features, were also assessed on the 10th postoperative day using liver biopsy specimens. Histological parenchymal dysfunction, especially in the centrilobular area, in terms of cholestasis, centrilobular necroinflammation, central vein fibrosis, steatosis, mononuclear infiltrates, and hepatocyte ballooning, was more prominent in group L than in group H, while that in the portal area was similar between the 2 study groups. Significant negative linear correlations were observed between LAI and parenchymal dysfunction scores (r = 0.486, P < 0.001). Group L patients showed lower 1‐year survival (69.7%) than group H patients (95.8%; P = 0.0002). Moreover, group H patients died with a functioning graft (n = 3), whereas group L patients died of graft failure (n = 6). After multivariate analysis, LAI alone remained independently associated with 1‐year mortality (P = 0.014; odds ratio = 0.845; 95% confidence interval, 0.739‐0.967). The sensitivity and specificity of LAI were 84.6% and 75%, respectively, and LAI outperformed MELD score as a predictor of 1‐year mortality after LDLT by receiver operating characteristic curve analysis. In conclusion, LAI, as determined by unenhanced CT 10 days after LDLT, well predicts 1‐year patient survival after LDLT. Liver Transpl 12:1403‐1411, 2006.

The clinical significance of early histological rejection with or without biochemical abnormality in adult living donor liver transplantation for hepatitis B virus related end stage liver disease.

There is no agreement regarding the treatment of early allograft rejection (EAR) in adult living donor liver transplantation (LDLT). A protocol biopsy was performed in 62 adult LDLT recipients. Twenty‐one patients (33.9%) had histological evidence of EAR. Of these, 14 patients had biochemical abnormalities and seven patients had no associated biochemical abnormalities. None of the seven patients with subclinical EAR (11.3% of the entire study population) were treated, and no subsequent rejection was observed. Gender mismatch (female‐to‐male) was the single independent risk factor for histological EAR [odds ratio (OR) = 13.458; 95% confidence interval (CI), 1.836–98.649] and the cumulative probability for a subsequent rejection was higher in patients with EAR (OR = 11.085; 95% CI, 1.221–100.654). However, the actuarial 1 year patient and graft survival rate in patients with EAR (81.0% and 85.5%) were similar to those without EAR (92.7% and 97.25%; P = 0.127 and 0.302, respectively). The presence of an initial biochemical abnormality was an independent risk factor for both a decreased patient survival (OR = 5.827; 95% CI, 1.095–31.017; P = 0.039) and graft loss (OR = 20.646; 95% CI, 2.044–208.524; P = 0.010). Subsequent rejection developed more frequently in patients with EAR. However, the survival is not determined by the presence of EAR but by the presence of a biochemical abnormality.

Hypophosphatemia after live donor right hepatectomy

BACKGROUND It is known that hypophosphatemia can frequently develop after hepatectomy and may result from an increased renal phosphate leak. However, its clinical significance has not been well defined in live donor right hepatectomy (LDRH). The purpose of this study was to investigate the correlation between postoperative hypophosphatemia and both donor morbidity and the degree of hepatic resection in LDRH. METHODS In all, 88 live liver donors were enrolled, who had undergone right hemihepatectomy between January 2002 and December 2005. Based on the severity of the postoperative hypophosphatemia, we divided the donors into 3 groups: mild (1.5-2.5 mg/dL, n = 30), moderate (1.0-1.5 mg/dL, n = 41), and severe (<1.0 mg/dL, n = 17), and we compared the incidence of complications among these groups. In addition, we investigated the possible correlation between the nadir phosphorus levels and both remnant liver volume and alkaline phosphate (ALP) levels. RESULTS All donors developed hypophosphatemia postoperatively. The mean value of the nadir phosphorus levels was 1.4 +/- 0.04 mg/dL. However, no significant difference was observed in the incidence of postoperative complications among the hypophosphatemia groups. The phosphorus level was positively correlated with the remnant liver volume (r = 0.389, P < 0.001), but it was negatively correlated with a postoperative increase in the ALP (r = -0.276, P = 0.014). CONCLUSIONS Hypophosphatemia developed very frequently after LDRH. However, transient hypophosphatemia was unlikely to lead to severe complications in healthy donors. Therefore, based on the serum level, oral or intravenous phosphorus replacement treatment might be more appropriate than routine aggressive replacement by TPN. In addition, although the factors responsible for posthepatectomy hypophosphatemia have not been identified, they might be substances that are associated with hepatic regeneration.