Arguments for a selective approach of preoperative portal vein embolization before major hepatic resection

Preoperative PVE can induce hypertrophy of the future liver remnant volume resulting in a decrease of surgical risk after major hepatic resection. However, the number of patients with normal liver at risk is small and there is no arguments for inducing hypertrophy before standard right hepatectomy. Therefore, in patients with normal liver PVE is indicated in patients in whom very extended liver resection or associated major gastro-intestinal surgery is planned. In patients with chronic liver disease and in those with injuried liver (chemotherapy, major steatosis, cholestasis), PVE is indicated before major liver resection.     

Application of preoperative portal vein embolization before major hepatic resection in patients with normal or abnormal liver parenchyma.

BACKGROUND: Clinical parameters influencing the effect of preoperative portal vein embolization (PVE) in hypertrophying the nonembolized lobe of patients with either normal or abnormal liver parenchyma and its effect upon portal pressure were examined to identify the patient population for whom this approach is most suited. METHODS: The study population included 43 patients undergoing major hepatectomy after PVE. Patients were divided into 2 groups according to their liver parenchyma: 17 patients with normal liver parenchyma (N group) and 26 patients with damaged liver parenchyma due to viral hepatitis (D group). We calculated the correlation between volumetric increases in the nonembolized (left) lobe after PVE (hypertrophic ratio = post-PVE left lobe volume/pre-PVE left lobe volume) using computed tomography volumetry before and 2 weeks after PVE. Clinical parameters also were examined to identify those parameters modifying the hypertrophic ratio in each group, and changes in portal pressure by PVE and the subsequent hepatectomy were recorded. Finally, by comparing patients with or without postoperative liver failure after hepatectomy, the influence of the hypertrophic ratio and portal pressure on the outcome of subsequent hepatectomy was examined. RESULTS: The hypertrophic ratio was 1.34 +/- 0.23 in the N group, and 1.25 +/- 0.21 in the D group. This difference was not significant. Multiple regression analysis revealed that the parenchymal volumetric rate of the right lobe (PVR) in the D group and both PVR and prothrombin time in the N group were independent parameters predicting the hypertrophic ratio. The portal pressure increased immediately after PVE and was similar in both groups to levels after hepatectomy. Six patients in the D group experienced postoperative liver dysfunction. In 5 of these 6 patients, the hypertrophic ratio was below 1.2, and the portal pressure was higher than that in patients without liver dysfunction. CONCLUSIONS: PVE induces hypertrophy of the nonembolized lobe of both abnormal and normal liver parenchyma, and the effect was predictable. Postoperative liver failure appeared to be more severe in patients having a lower hypertrophic ratio and higher portal pressure in abnormal liver parenchyma, however. PVE also may have diagnostic use in predicting portal pressure after hepatectomy, which may be associated with surgical outcome.     

Acute renal failure prior to the onset of hepatic encephalopathy in fulminant hepatitis

Summary: We investigated the clinical characteristics of eight patients with fulminant hepatitis who developed acute renal failure (ARF). They were divided into two groups according to the time point when ARF occurred in the course of the disease: (i) group 1 ( n =4), ARF occurred prior to the onset of hepatic encephalopathy; and (ii) group 2 ( n =4), ARF occurred after the onset of hepatic encephalopathy. All cases in group 1 had an acute type of fulminant hepatitis, whereas a subacute type was present in the patients in group 2. All cases in group 1 and two cases in group 2 were given non-steroidal antiinflammatory drugs before the onset of ARF. Urinary findings and/or renal biopsy findings suggested that acute tubular necrosis was the cause of ARF in group 1. Three patients in group 1 and none in group 2 recovered from both ARF and fulminant hepatitis. Although it is well-known that a patient with fulminant hepatic failure complicated by ARF has a poor prognosis, our findings suggest that ARF that occurs prior to the onset of hepatic encephalopathy in acute type of viral fulminant hepatitis is not a determinant of the poor prognosis, and that the prognosis will be improved by intensive care.     

Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: A preliminary report

With the aim of minimizing postoperative liver dysfunction and promoting increased resectability, we employed portal vein embolization (PVE). In this study, the effect of PVE on major hepatic resection for advanced-stage hepatocellular carcinoma (HCC) in injured livers was evaluated. PVE was performed prior to hepatectomy in 13 patients with stage III and IV HCCs. Following PVE, right trisegmentectomy was performed in 3 patients, extended right lobectomy in 3 and right lobectomy in 7. To evaluate the effect of PVE, the changes in liver functional capacity and estimated remnant liver volume (ERLV), determined by computed tomography, were examined before and after PVE. The operative morbility, mortality, and survival rates after hepatectomy were also assessed. By 2 weeks after PVE, ERLV had increased in all patients, by an average of 28%, and the mean resection rates had decreased from 70.0% to 62.2%. Postoperatively, the 30-day mortality rate was 15.3%, and the 1- and 2-year survival rates were 69% and 46%, respectively. The results of this study indicate that resectability can be increased, and major hepatectomy can be made safer by employing PVE preoperatively, in view of the fact that major hepatectomy was not considered feasible without PVE in these patients.     

原位肝移植加人工肝支持疗法治疗暴发性肝功能衰竭

目的 探讨原位肝移植加入人工肝支持疗法对暴发性肝功能衰竭的疗效及非生物型人工肝支持系统在暴发性肝功能衰竭肝移植术前准备中的作用。方法 本组7例暴发性肝功能衰竭患者,均有不同程度的肝昏迷,黄疸,腹水,肝功能损害,出血倾向,在等待供肝的过程中分别接受2-20次非生物型人工肝支持疗法,供肝到达后行原位肝移植术,结果 人工肝支持治疗后患者血清胆红素明显下降,腹水明显减少,部分病人肝性脑病有所好转,7例均顺利行肝移植,5例存活3-290个月,其中3例已存活1年半以上,并已恢复正常工作,2例术前有肝肾综合征者,术后3d死亡,其中1例并发急性重症胰腺炎。结论 原位肝移植加入工肝支持疗法是暴发性肝功能衰竭的有效方法,术前人工肝支持可作为暴发性肝功能衰竭等待供肝期间的桥梁,并可改善病情减少肝移植的危险因素。     

肝移植治疗暴发性肝衰肝性脑病的临床研究

目的 总结肝移植治疗暴发性肝衰肝性脑病的临床经验。方法 回顾性分析４例暴发性肝衰肝性病病人行肝移植手术治疗的临床资料。结果 肝移植治疗暴发性肝衰肝性脑病１个月存活率７５％（３／４）,超过３个月存活率为５０％（２／４）。结论 肝移植是治疗暴发性肝衰肝性脑病的一种有效方法,暴发性肝衰肝性脑病不是肝移植手术的禁忌证。     

Serum protein binding of propofol in patients with renal failure or hepatic cirrhosis

Background: Serum protein binding is a limiting factor in the access of drugs to the central nervous system. Disease-induced modifications of the degree of binding may influence the effect of anesthetic drugs. Methods: The protein binding of propofol, an intravenous anaesthetic agent which is highly bound to serum albumin, has been investigated in serum samples from healthy volunteers, from patients with chronic renal failure not undergoing hemodialysis, from patients with chronic renal failure included in a regular hemodialysis program, and from patients with hepatic cirrhosis. Protein binding was determined by the ultrafiltration technique using an Amicon Micropartition System, MPS-1. Results: The percentage of unbound propofol (mean(SD)) in healthy volunteers (n=16) was 0.98 (0.48) % showing a high interindividual variability. Chronic renal failure did not significantly modify serum protein binding of propofol. In the chronic renal failure group not undergoing regular hemodialysis (n=>9), unbound propofol was 0.92 (0.34) %. In addition, patients in periodic dialysis did not show changes in propofol binding either compared before (1.11 (0.33) %; n=13) or after hemodialysis (0.87 (0.38) %; n=12). A slight decrease in albumin concentration was found in all renal patients (P<0.05) in comparison to healthy volunteers. Creatinine and urea concentrations were higher in these patients (P<0.01) but in the postdialysis group, the differences in urea levels were not significant when compared with those of volunteers. No changes in the degree of propofol binding were observed in patients with hepatic cirrhosis (0.97 (0.30) %; n=14) when compared with the group of healthy volunteers. Significant differences were observed in albumin (P<0.01) and bilirubin (P<0.05) concentrations. Considering all subjects, the degree of binding did not correlate with biomedical data. Conclusion: Due to the the absence of significant changes in the protein binding it is unlikely that there will be an exaggerated pharmacological response in patients with renal and hepatic disease following the administration of a standard propofol dose, although due to interpatient variability careful titration can be recommended.     

Tumor size and operative risks of extended right-sided hepatic resection for hepatocellular carcinoma: implication for preoperative portal vein embolization

HYPOTHESIS: Major hepatic resection for hepatocellular carcinoma (HCC) is associated with high operative morbidity and mortality, especially in patients with underlying chronic liver disease. The present study evaluated the factors associated with increased operative risks in patients who underwent extended right-sided hepatic resection for HCC. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A retrospective study was performed on 172 patients who underwent extended right-sided hepatic resection of more than 4 Couinaud segments for HCC during a 16-year period (January 1, 1989, to December 31, 2004) to evaluate the clinical factors associated with operative morbidity and mortality. MAIN OUTCOME MEASURE: Risk factors associated with hospital mortality and major operative morbidity. RESULTS: The overall major morbidity and hospital mortality rates were 14.0% and 8.1%, respectively. On multivariate analysis, small tumor size, conventional-approach hepatectomy, Child-Pugh grade B cirrhosis, and preexisting tumor rupture were the independent factors significantly associated with an increased risk of operative mortality. Discriminant analysis showed that a tumor size smaller than 10 cm significantly increased the risk of operative mortality compared with larger tumors (17.2% vs 3.5%; P = .046). CONCLUSIONS: Anterior approach is the preferred technique for extended right-sided hepatic resection for HCC. Increased risk of operative mortality was identified in patients who had a small tumor, which was associated with the resection of a large volume of functioning liver parenchyma. Preoperative portal vein embolization should be considered in this group of patients to enhance atrophy of the right lobe and hypertrophy of the future liver remnant to minimize the operative risk.     

Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat

BACKGROUND: Optimization of the conditions for regeneration is a major goal in the management of patients with acute liver failure (ALF). Previous observations suggested that hyperoxygenation of the liver may improve its regenerative capacity. Thus, this study aimed to determine whether an additional supply of oxygenated blood achieved by portal vein arterialization (PVA) is protective in rat ALF caused by toxin administration or hepatectomy. METHODS: Sprague-Dawley rats were subjected or not to PVA after CCl(4) intoxication or extended hepatectomy. PVA was performed by interposing a stent between the left renal artery and splenic vein after left nephrectomy and splenectomy. Liver injury was evaluated by the serum ALT level and necrotic cell count. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine (BrdU) staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. In the CCl(4)-induced ALF, serum ALT levels and necrosis were significantly reduced in arterialized than non-arterialized rats. PVA greatly promotes liver regeneration in both models. Finally, PVA significantly improved survival compared to controls (CCl(4): 100 versus 40%; 90% hepatectomy: 90 versus 30%). Interestingly, in the CCl(4)-induced ALF, survival was 100% even when the shunt was closed after 48 h. CONCLUSION: These data indicate that the additional supply of arterial oxygenated blood through PVA promotes a rapid regeneration leading to the resolution of toxic-induced massive liver necrosis and a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool for optimizing hepatocyte regeneration.     

A good model of hepatic failure after excessive hepatectomy in mice

AIMS: This study was intended to establish in mice: 1) a safety limit for the extent of hepatectomy and 2) the extent of hepatectomy invariably causing fatal hepatic failure, to facilitate gene expression analysis. MATERIALS AND METHODS: In 70%-hepatectomy, the left lateral and median lobes were removed, and in 90%-hepatectomy, all lobes except the caudate were resected. One-week survival rates, serum concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin were measured. Histological examinations were performed using hematoxylin and eosin staining, and immunohistochemical tests were done with antibody against Ki-67 antigen. RESULTS: All of the 70%-hepatectomized mice were alive at 1 week, but the 90%-hepatectomized mice all died within 24 h after hepatectomy. Serum aminotransferase and total bilirubin levels were significantly higher in the 90%-hepatectomized mice than in the 70%-hepatectomized mice. Liver histology revealed more prominent vacuolar degeneration in the former. Ki67-positive hepatocytes appeared and proliferated immediately after 70%-hepatectomy, but few were observed in the 70%-hepatectomized mice. CONCLUSION: We established 90%-hepatectomy as the safety limit for murine hepatectomy and as a model for liver regeneration, and 90%-hepatectomy as a "fatal hepatic failure level."     

Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery from hepatic coma after liver transplantation.     

The importance of orthotopic liver transplantation in acute hepatic failure

Selection of patients with acute hepatic failure for liver transplantation remains difficult, and there is no definite proof of a survival effect. We therefore did a retrospective study in 75 consecutive patients referred over a 12-year period. In two-thirds we identified a cause, mostly viruses or drugs. Patients were grouped by the Clichy and King's College criteria. In 20 there was no indication for transplantation. Of the 5 with autoimmune hepatitis, 3 died, significantly differing from the other 15 ( P = 0.009). The remaining 55 met our criteria, except 1. All 9 patients with absolute contraindications died. Of the 46 enlisted, 7 died without transplantation. One-year survival after transplantation was 69%, compared with 58% by "intention to treat." For patients enlisted, transplantation reduced mortality by 78% ( P = 0.069). The Clichy and King's College criteria reliably predict survival without transplantation, except in autoimmune hepatitis. Our study strongly suggests that transplantation improves survival.     

Paracetamol-induced fulminant hepatic failure in a child after 5 days of therapeutic doses

We report the case of a two and a half year-old girl who developed fulminant hepatic failure following 5 days of regular oral ingestion of paracetamol, approximately 90 mg x kg-1 x day-1. She presented with the typical findings of hepatomegaly, encephalopathy, high ammonia levels, high transaminases, hypoglycaemia and lactic acidosis. After stabilization, she was transferred to a specialist paediatric liver failure unit and fortunately she made a full recovery with intensive medical management.     

肝移植治疗药物性急性肝衰竭的体会（附8例报告）

目的 探讨肝移植治疗药物性急性肝衰竭的疗效.方法 药物性急性肝衰竭患者8例,术前肝功能Child-Pugh分级均为C级,均合并肝性脑病（Ⅲ～Ⅳ期）.所有患者均行经典原位肝移植,供体均为尸体供肝,均未行静脉转流.术后予免疫诱导、免疫抑制治疗,并予抗感染及支持治疗.结果 8例患者均顺利完成肝移植手术.术后1例女性患者并发原发性移植肝无功能,死亡.余7例患者于术后16～72 h苏醒.1例发生胆道铸型结石,手术取石效果不佳,予再次肝移植,行胆总管空肠吻合术,术后发生吻合口漏死亡.其余6例存活患者均痊愈,生活状况良好.其中2例曾发生急性呼吸窘迫综合征,行气管切开、呼吸机辅助呼吸,最后康复出院.结论 对于保守治疗无效的药物性急性肝衰竭,肝移植是唯一有效的治疗措施.     

Isoniazid-related fulminant hepatic failure in a child: assessment of the native liver's early regeneration after auxiliary partial orthotopic liver transplantation

Abstract We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft-hepatic artery thrombosis (HAT) and the NL's incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF     

肝蒂联合右肝静脉阻断在巨块型肝癌切除中的应用

目的评估肝蒂联合右肝静脉阻断在巨块型肝癌切除中的作用和意义。方法对2003年2月至2006年8月中南大学湘雅二医院肝胆外科收治的138例位于右半肝及中央型的巨大肝癌行肝蒂联合右肝静脉阻断,观察肝脏血流阻断时间、手术时间、术中出血量、术后肝功能的变化及术后并发症。结果135例在肝外游离出右肝静脉并加以阻断,3例以小的心耳钳沿腔静脉方向纵行夹住右肝静脉阻断出肝血流。所有病例右侧均顺利阻断肝蒂。肝脏血流阻断时间平均为(18±6)min,手术时间平均为(180±45)min,术中出血400~1200mL,56例术中未输血。术后无一例发生肝功能衰竭。术后膈下感染2例,胆漏4例,经引流自愈。结论在巨块型肝癌切除中,肝蒂联合右肝静脉阻断技术可以有效地减少术中出血,降低术后肝功能衰竭的发生率。     

Immediate early genes and p21 regulation in liver of rats with acute hepatic failure

It has been observed that liver regeneration in acute hepatic failure (AHF) is suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism regulating this inhibition is not known. We previously reported that in AHF rats, hepatocyte proliferation was significantly impaired with elevation in serum IL-6, TGF-beta1, and HGF [Kamohara et al. Biochem Biophys Res Commun 2000;273(1):129-35]. Following either 70% partial hepatectomy (PH) or liver injury, quiescent mature hepatocytes are "primed" to re-enter the cell cycle. The process of "priming" appears to be triggered by extracellular cytokines (IL-6 and TNF-alpha) and is characterized by expression of immediate early genes. Under the stimulation of growth factors such as HGF, "primed" hepatocytes exit the G1 phase of the cell cycle. G1-associated cyclins and their inhibitors play a pivotal role in G1/S cell cycle transition. Here, we demonstrate that immediate early gene (i.e. c-myc, c-fos) expression and AP-1 activity are preserved in AHF rat livers despite absence of hepatocyte proliferation. In contrast, p21 mRNA and protein are both over-expressed in AHF livers compared to livers from rats undergoing PH; this elevation leads to inhibition in Cdk2 activity, resulting in G1 cell cycle arrest and inhibition of regeneration.     

肝动脉和门静脉高位分支双重处理对犬肝脏结构和功能的影响

目的 观察肝动脉和门静脉分支双重处理后犬肝脏结构和功能的改变。方法 杂种犬25只。随机分成假手术对照组和实验组,实验组进行肝动脉左支结扎和门静脉左支缩窄70％。分别于术后1,2,3,7和14d处死动物,观察肝脏大体结构的变化,分别称取左右半肝脏的质量,检测肝脏功能。光学显微镜下观察肝脏显微结构改变,电镜下观察肝脏超微结构改变。结果 肝动脉左支结扎和门静脉左支缩窄70％后,左半肝脏呈进行性萎缩变小,右半肝脏则成比例地代偿性增生,在整个观察过程中,全肝的总质量维持恒定。肝脏功能在术后2-3d时有轻度异常,很快即恢复正常。光镜下左半肝脏在早期出现少量的点、片状坏死。坏死周围出现大量的肝细胞凋亡,右半肝脏的肝小叶结构保持完整,术后肝细胞的增殖明显,有较多的分裂相存在。电镜下左半肝脏可见到典型的肝细胞凋亡,晚期呈明显纤维化改变。结论 肝动脉左支结扎和门静脉左支缩窄70％后。左半肝脏由于肝细胞大量凋亡呈进行性萎缩变小,右半肝脏则成比例地代偿性增生肥大,全肝的总质量和肝脏功能保持正常。