Bacterial clearance in the intact and regenerating liver

The Kupffer cells in the liver play an important role in reticuloendothelial system (RES) function by clearing particulate matter and bacteria from the blood stream. While hepatocyte regeneration and function have been extensively studied following partial hepatectomy, little information is available concerning RES function in the regenerating liver. This study investigates hepatic RES function by evaluating bacterial clearance (live E. coli) in the intact and regenerating liver. Thirty-four young male Sprague Dawley rats were studied. Twenty-two animals underwent a standard 70% partial hepatectomy using ligature technique and 12 had a sham operation. Both groups of rats received 10(9) organism of S35 labeled E coli, intravenously at 24 hours, 72 hours, 2 1/2 weeks, and 6 weeks postoperatively. Rats were killed 10 minutes following injection and liver, lung, spleen, and kidney harvested, fixed, and radioactivity was determined using a scintillation spectrometer interfaced with a micro-computer counting the S35 radiolabel. The total organ count of trapped bacteria in liver in partially hepatectomized rats was lower than intact controls at 24 hours (22.0% v 46.4%, P less than .01), but was similar at 72 hours, 2 1/2 weeks, and 6 weeks. Partial hepatectomy increased the amount of bacterial trapping in the lung at 24 hours (11.3% v 1.7%, P less than .01) and 72 hours (10.1% v 1.7%, P less than .05) and returned to normal at 2 1/2 weeks and 6 weeks. Splenic activity was increased following hepatectomy at 2 1/2 weeks. Renal clearance was increased at 72 hours and 2 1/2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝部分切除术后大鼠认知功能及β淀粉样蛋白的变化

目的 评价大鼠肝部分切除术后认知功能及β淀粉样蛋白(Ap)的变化.方法 健康雄性sD大鼠70只,体重200～250 g,随机分为3组:对照组(C组,n=12)、麻醉组(A组,n=29)和肝部分切除术组(PH组,n=29).A组和PH组于术后1 d(T1)和7 d(T3)时各取7只大鼠,采用Y型迷宫检测术后第1、2、3、7、8、9天时学习记忆能力;于术后1 d(T1)、3 d(T2)和7 d(T3)时取5只大鼠,取左侧海马,并断尾取血,测定Aβ表达;取右侧海马采用荧光定量PCR测定App mRNA表达.结果 与C组相比,PH组术后学习记忆能力下降,T1,3时血清Aβ浓度降低,T1-3,时海马Aβ含量升高,TI时App770mRNA含量升高(P＜0.05);与A组相比,PH组术后学习记忆能力下降,T1,3时血清Aβ浓度降低,T1-3时海马Aβ含量升高,T1时App770 mRNA含量升高(P＜0.05).结论 肝部分切除术后大鼠发生短期认知功能减退,可能与海马Aβ含量升高有关.     

Impact of hepatic vein deprivation on liver regeneration and function after major hepatectomy

Background and aims In extended liver resections, the preservation of vascular and biliary structures of the entire remnant liver is of paramount importance. The impact of venous outflow impairment and its consequences for liver regeneration and function are still a matter of debate. Materials and methods Rats (n = 75) were subjected to a 90% partial hepatectomy (PH), to a 70% liver resection with narrowing of the hepatic outflow of an additional 20% parenchyma (70%+ PH) or to an anatomic 70% PH. Postoperatively hepatocyte proliferation (Ki-67), liver function and survival were assessed. Gene expression analysis for markers of regeneration was determined by in-house complementary (DNA) arrays and quantitative real-time polymerase chain reaction (RT-PCR). Results Ninety percent PH led to a greater regenerative response as shown Ki-67 compared to animals with a 70%+PH (p < 0.05). However, liver function was equally impaired in both groups. Rats with 70% PH showed a greater proliferation index with less hepatic injury and better liver function. While mortality was 0% in the group of 70% PH, rats with 90% PH and 70+PH had a reduced survival of 75% (p < 0.05) Conclusion Venous outflow obstruction leads to an impairment of liver regeneration and liver function. In cases with critically small liver remnants, restoration of an adequate venous outflow may be mandatory.     

The three different phases of reticuloendothelial system phagocytic function in rats with liver injury

In the present study, reticuloendothelial system (RES) phagocytic function of rats with partial hepatectomy or experimentally induced liver cirrhosis was investigated by determining the phagocytic index, the opsonic index, and uptake rate in liver, spleen, and lung of a 51Cr-labeled endotoxin-injected rat. In both the partially hepatectomized and the cirrhotic rats, all three indicators varied markedly according to the elapsed period since liver injury. The changes in RES phagocytic function were classified into three different phases: compromised, compensatory, and enhanced. The compromised phase, consisting of a decrease in the phagocytic index, was observed during the first 24 hr after 67% hepatectomy and in advanced liver cirrhosis. This represented the failure of RES phagocytic function. The compensatory phase, in which the phagocytic index was maintained at nearly normal levels mainly by a compensatory enhancement in the opsonic index, was seen during the first to second postoperative day and in moderate liver cirrhosis. The enhanced phase, with a high phagocytic index, was observed from Day 4 to approximately Day 14 after surgery, and in the cases of mild liver damage. In the compromised and compensatory phases, the liver uptake rate was significantly decreased compared with the control. However, the uptake in the spleen and lung were markedly increased. In conclusion, the phagocytic function of the RES was significantly affected to a degree which changed with the extent of liver damage.     

Reticuloendothelial System Function Following Acute Liver Failure Induced by 90% Hepatectomy in the Rat

Sepsis and bacterial infections are frequent complications of acute liver failure and following major liver resection. The mechanisms underlying this phenomenon are unclear. In this study, RES function and blood clearance of radiolabelled E. coli was immediately impaired following 90% hepatectomy, although the reduction in liver volume resulted in an increase in splenic (temporary) and pulmonary (persisting) uptake. A significant correlation between liver function and host RES function was observed. The uptake capacity of the RES in the liver remnant and spleen did not correlate with subserosal blood flow. The uptake in the brain gradually increased with time, paralleling an increased leakage across the blood-brain barrier. Thus, a significantly impaired RES function resulted from experimental 90% hepatectomy-induced acute liver failure, which might explain the high incidence of septic events in the clinical situation.     

Effect of activation of the reticuloendothelial system on hepatocyte regeneration in partially hepatectomized rats

Enhanced effect on rat hepatocyte regeneration through activation of the reticuloendothelial system (RES) was investigated. RES was activated using by OK-432 and the phagocytic activity (K-value) increased 2-fold over control rats 24 hours after intraperitoneal injection of OK-432. In OK-432 treated rats, the amount of cyclic AMP in the regenerating liver also increased 1.5-fold higher than in control rats 14 hours after hepatectomy. After 70% partial hepatectomy, liver DNA synthesis in OK-432 treated rats increased 2 to 5-fold higher than in control rats. There was a good correlation between the K-value before hepatectomy and DNA synthesis 24 hours after hepatectomy (r = 0.96). Therefore the RES is one of the most important regulatory factors in liver regeneration. Augmentation of RES before hepatectomy may prevent hepatic failure after resection in liver diseases.     

Augmentation of cell-mediated cytotoxicity following 50% partial hepatectomy

The cytolytic responses of C3H/HeJ mice after 50% hepatectomy (PH) were assessed in a 4-hr 51Cr-release assay. Spleen cells (SC) (50 x 10(6] from normal or PH C3H/HeJ (H-2k) mice were sensitized with equal numbers of irradiated allogeneic DBA/2 (H-2d) spleen cells in a five-day mixed lymphocyte culture. Generated cytolytic activity was measured against 51Cr-labeled P815 mastocytoma (H-2d) and EL4 lymphoma (H-2b) target cells. The wet weight and cell numbers per spleen following 50% partial hepatectomy were 70% and 75% higher than the control values for the first 20 days, and then returned to normal levels by 21 days. The cytolysis by spleen cells from 2-, 14-, and 31-day PH mice were 89.3 +/- 0.7, 86.9 +/- 5.3, and 90.1 +/- 1.3%, respectively, compared with control (sham-operated) values of 56.0 +/- 1.0, 57.0 +/- 2.0, and 49.9 +/- 7.0% (P less than 0.03 at E/T 100:1). This enhanced cytolysis by PH spleen cells remained high for at least 118 days after the liver resection before returning to control levels by 268 days. Cytolytic effector cells in PH SC were generated at least 24 hr earlier than in control SC. When normal and PH cytolysis were compared following primary and secondary in vitro sensitization, the cytolytic levels of primarily-sensitized PH spleen cells were comparable to secondarily sensitized normal spleen cells. Furthermore, the primarily sensitized normal spleen cells did not show crossreactive cytolysis with EL4 target cells (H-2b), while both the primarily sensitized PH spleen cells and the secondarily sensitized normal spleen cells were significantly cross-reactive against the third party EL4 target cells. Adherent PH spleen cells appear to be responsible for this augmented cytolytic capacity since their coculture with normal nonadherent responder spleen cells increased control cytolysis by approximately 30%. These studied demonstrate that, following 50% partial hepatectomy, there is an immediate and sustained increase in the allospecific cytolytic response.     

Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance

BACKGROUND: Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed. METHODS: Buffalo rats (n = 7 to 12/group) were treated with saline, 40 microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test. RESULTS: MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P <. 05). MTP-PE administration increased macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P <.005). CONCLUSIONS: MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.     

广泛肝切除联合肝固有动脉切除对正常大鼠及梗阻性黄疸大鼠的影响

目的 探索在正常及高胆红素血症情况下,大鼠70%肝切除联合肝固有动脉切除对肝功能、肝细胞能量代谢以及肝再生和细胞凋亡的影响.方法 雄性成年SD大鼠133只,将其中40只分为2组,每组20只,均行胆总管-十二指肠插管桥接,同时行70%肝切除或70%肝切除联合肝固有动脉切除.另87只行胆总管结扎制备梗阻性黄疸模型.5 d后手术分为70%联合肝切除胆肠再通内引流组,及70%肝切除联合肝固有动脉切除、胆肠再通内引流2组.动态观察术后24 h、72 h、7 d肝功能和肝细胞能量代谢、肝组织HGF和bcl-2 mRNA含量及其蛋白表达、肝细胞增殖指数和凋亡指数的变化,并统计各组死亡率.另取6只作为假手术组,测定术后0 h肝功能和肝细胞能量指标.结果 正常大鼠能够耐受70%肝切除联合肝动脉切除,术后肝细胞能量代谢和肝功能迅速恢复正常,肝再生良好.高胆红素血症时,大鼠术后肝再生受抑制,细胞凋亡增多.较之70%肝切除组,70%肝切除联合肝固有动脉切除组对肝细胞能量代谢的影响更为显著,术后肝功能恶化,肝组织HGF和Bcl-2 mRNA含量显著减少,肝再生明显受抑制,细胞凋亡增多,死亡率显著增高(P<0.05).结论 正常大鼠70%肝切除联合肝动脉切除术后肝再生不受影响,高胆红素血症时,70%肝切除联合肝动脉切除的大鼠死亡率高,因此术前引流减黄应是必要的措施.     

Decreased reticuloendothelial phagocytic capacity in cirrhotic and portacaval shunt rats

In cirrhosis, the phagocytic function of the reticuloendothelial system (RES) is decreased. In order to investigate the mechanisms of the hepatic reduced phagocytic activity present in cirrhosis, the hepatic and splenic uptake of 51Cr sheep red blood cells (SRBC) and of colloidal carbon was measured in three groups of Sprague-Dawley rats. Group 1 consisted of 42 control rats, group 2 of 36 rats with end-to-side portacaval shunt and group 3 of 24 rats with carbon tetrachloride-induced cirrhosis. The hepatic uptake of 51Cr SRBC and of colloidal carbon was significantly (p less than 0.001) reduced in cirrhotic rats (group 3). Conversely, in rats with a portacaval shunt and a noncirrhotic liver (group 2), the hepatic uptake of 51Cr SRBC was moderately reduced, whereas the colloidal carbon hepatic uptake was not found to be decreased. These results suggest that the decreased RES phagocytic activity observed in cirrhotic rats is only partially due to portacaval shunt and that an intrinsic defective activity of hepatic phagocytic cells is probably present.     

Lack of protection of ischaemic preconditioning in the rat model of major hepatectomy with ischaemia reperfusion injury

OBJECTIVE: To investigate the effects of ischaemic preconditioning (IP) on residual liver regeneration after major hepatectomy without portal blood bypass in rats, and to verify whether it can protect the residual liver from ischaemia reperfusion (IR) injury. METHODS: Ninety rats were randomized into three groups: Group PH, rats were subjected to 70% hepatectomy alone; Group IR, rats were subjected to 30 minutes of total hepatic ischaemia, and 70% hepatectomy was performed just before reperfusion; Group IP, rats were pretreated with IP (5/10 minutes). During the preoperative period and at 0.5, 6, 12, 24 and 48 hours after the operation, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured using an autoanalyser. Serum hyaluronic acid (HA) was measured by radioimmunoassay. Regenerated liver weight (RLW) of the rats was measured and the expressions of Ki-67 and cyclin D1 were determined by immunohistochemistry in remnant liver tissue. RESULTS: There were no significant differences in serum AST and ALT levels in all the groups before the operation. After partial hepatectomy, AST and ALT levels increased rapidly. From 0.5 to 24 hours after operation, serum AST and ALT levels were significantly higher in IP group rats than in PH and IR rats (p < 0.05). There were no significant differences in serum HA levels in all the groups before the operation. After partial hepatectomy, HA levels increased rapidly, reaching peak values at 12 hours. In the early stage (during 12 hours) after the operation, HA level was significantly higher in IP rats than in PH and IR rats (p < 0.05). The RLW of the rats rapidly increased after partial hepatectomy, and significantly decreased in IP rats compared with PH and IR rats (p < 0.05). Cyclin D1 and Ki-67 expression in all groups before the operation were low and were not significantly different. After partial hepatectomy, they rapidly increased. The expression of Ki-67 and cyclin D1 reached a peak at 24 hours after the operation in PH rats, and they were significantly higher compared with IR and IP rats (p < 0.05). In groups IR and IP, the expression of cyclin D1 and Ki-67 reached peak values at 48 hours. A significant decrease (p < 0.05) was observed after 24 and 48 hours of reperfusion in group IP compared with groups PH and IR. CONCLUSION: IP impairs residual liver regeneration after major hepatectomy without portal blood bypass in rats, and protection from IR injury disappears. IP-induced hyperperfusion may be the cause of reduced liver regeneration.     

Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.     

Pathophysiology and treatment of multiple organ failure among hepatectomized cirrhotic patients

Our previous studies have claimed that cirrhotic rats, induced with CCl4, showed depressed reticuloendothelial system (RES) function and increased susceptibility to infection. We have also shown that OK-432, a non-specific immunopotentiator, and ATP-MgCl2, which improves depressed intracellular energy metabolism, improve RES function of cirrhotic rats and that thereby improve survival following peritonitis or hepatectomy. The present study was undertaken to investigate whether OK-432 or ATP-MgCl2 could be beneficial for the prevention of multiple organ failure (MOF) following hepatectomy among the cirrhotics. The cirrhotics with hepatocellular carcinoma, who underwent partial hepatectomy (segmentectomy or subsegmentectomy) were given OK-432 (5 KE/day for 4 days) preoperatively or ATP-MgCl2 (50 mumole/kg) within 24 hours following the operation. The rates of postoperative pulmonary complication and the operative mortality were compared among OK-432 group, ATP-MgCl2 group and controls. The rates of posthepatectomy pulmonary complication and operative mortality were decreased with these treatments compared to the controls. The RES function was also improved with these treatments. These data suggest that the cirrhotic patients are the immunocompromised hosts showing the depressed RES function and that the enhancement of RES function with OK-432 or ATP-MgCl2 is beneficial for the prevention of posthepatectomy MOF among cirrhotics.     

Implication of B lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats

BACKGROUND: Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear. METHODS: We used lymphopenic (L(-)) rats by single administration of anti-rat lymphocyte serum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) micro-chain from birth, and their vehicle controls. These animals were subjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5 mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatic tissue deposition of IgM or C3 was assessed with immunohistochemistry. RESULTS: The 24-h survival rate in control animals was 20%, whereas those in L(-), T(-), and B (-) animals were 80, 0, and 100%, respectively. Lymphocyte-sufficient control (L(+)) and B cell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-alpha levels 1 h after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 h after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 h after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM, and CH50 levels, showing less histological liver damage. CONCLUSION: B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy.     

Experimental study of endotoxemia and reticuloendothelial system in hepatectomized cirrhotic rats

To investigate acute hepatic failure associated with endotoxemia and reticuloendothelial system (RES) in hepatectomized cirrhotic patients, lipopolysaccharide (LPS) at the dose of 0.2 micrograms/100gBW was injected intravenously into the 70% hepatectomized three groups of rats as follows; LC: rats with thioacetamide-induced liver cirrhosis, Control: rats with normal liver, LC + FN: cirrhotic rats with intravenous supplementation of fibronectin. 1) The survival rates at 24 hours after hepatectomy of each group of LC, Control and LC + FN were 0%, 100%, and 80%, respectively. Residual liver of group-LC revealed massive necrosis in histological study. 2) Phagocytic index (K) of injected 3H-labeled LPS were 0.100/min, 0.155/min and 0.146/min, respectively. 3) Uptake of injected 3H-labeled LPS at 15 minutes after injection was remarkably elevated into the liver compared with the lung and spleen in each group. Also uptakes into the liver per gram of tissue were 0.96% ID/g, 3.00% ID/g and 1.46% ID/g, respectively, and those per total organ were 5.95% ID/TO, 8.20% ID/TO and 9.21% ID/TO, respectively. 4) Level of plasma fibronectin decreased and that of serum total bile acid increased remarkably after injection of LPS in group-LC compared with the others. These results suggest the mortality of hepatic necrosis by LPS in group-LC is attributed to markedly reduced RES function especially in the liver, and supplementation of fibronectin decreases the mortality by enhancing RES function.     

Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice.

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.     

Deceleration of Regenerative Response Improves the Outcome of Rat with Massive Hepatectomy

Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS‐398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS‐398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS‐398 treatment. In the 90% PH model, administration of NS‐398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver.     

Effect of biliary decompression on reticuloendothelial function in jaundiced rats.

The recovery of reticuloendothelial system (RES) function following decompression of obstructive jaundice was studied using a rat model with bile duct ligation and side-to-side choledochoduodenostomy. Histopathological changes in the liver were still present 5 weeks after relief of jaundice, while results of liver function tests had returned to normal. RES function evaluated by the blood clearance and organ uptake of radiolabelled Escherichia coli using a corrected phagocytic index gradually returned to normal following biliary decompression. The severely impaired RES activity noted 1 week after operation may explain the increased incidence of sepsis and renal insufficiency in the early period after biliary surgery in jaundiced patients.