Adaptation of lenvatinib treatment in patients with hepatocellular carcinoma and portal vein tumor thrombosis.

PURPOSE: The aim of this study was to clarify the adaptation of lenvatinib treatment in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHOD: Fifty-three patients with HCC were treated with lenvatinib. Before and after treatment blood sampling, patients were examined by computed tomography and ultrasonography. In patients with portal trunk invasion (Vp4), the analysis focused on the degree of occlusion due to the tumor in the portal trunk. In patients without major PVTT {ie, invasion of the primary branch of the portal vein [Vp3] or Vp4}, portal blood flow volume was measured by Doppler analysis; however, Doppler analysis is difficult to perform in patients with major PVTT, so the time from administration of the contrast agent to when it reached the primary branch of the portal vein (portal vein arrival time) was evaluated with the contrast agent Sonazoid. RESULTS: Patients with Vp4 had a significantly worse prognosis than patients with Vp3 and a significant increase in Child-Pugh score at 2 months. Patients with major PVTT had a poor prognosis if the degree of occlusion of the portal trunk was 70% or more. In patients without major PVTT, portal blood flow was significantly decreased after administration of lenvatinib; and in patients with major PVTT, the hepatic artery and portal vein arrival times were significantly increased. CONCLUSION: Lenvatinib treatment should be avoided in patients with Vp4 with a high degree of portal trunk occlusion because of concerns about decreased portal blood flow.

Metformin Stimulates Intestinal Glycolysis and Lactate Release: A single-Dose Study of Metformin in Patients With Intrahepatic Portosystemic Stent.

The pharmacodynamic effects of metformin remain elusive, but several lines of evidence suggest a critical role of direct effects in the gastrointestinal (GI) tract. We investigated if metformin stimulates intestinal glucose metabolism and lactate release in the prehepatic circulation. We included eight patients with transjugular intrahepatic portosytemic stent in an open label study. Portal and arterialized peripheral blood was obtained before and 90 minutes after ingestion of 1,000 mg metformin. Metformin increased lactate concentrations by 23% (95% confidence interval (CI): 6-40) after 90 minutes in the portal vein. The plasma concentration of glucose, insulin, and C-peptide was higher in the portal vein compared with arterialized blood (P < 0.05, all) and was lowered at both sampling sites following metformin ingestion (P < 0.01, all). Plasma concentration of GLP-1 was 20% (95% CI: 2-38) higher in the portal vein at baseline and metformin increased the concentration with 11% (1.5 pM, P = 0.05). The median concentration of growth differentiation factor 15 was 10% (95% CI: 1-19) higher in the portal vein compared with arterialized blood. Ninety minutes after metformin administration, the median portal vein concentration increased to around 3,000 ng/mL with a mean portal/arterial ratio of 1.5 (95% CI: 1.2-1.8). Non-targeted metabolomics showed that metformin acutely affected benzoate-hippurate metabolism. A single-dose of metformin directly affects substrate metabolism in the upper GI tract in humans with direct stimulation of nonoxidative glucose metabolism. These data suggest glucose lowering effects of metformin can be intrinsically linked with the GI tract without hepatic uptake of the drug.

Effectiveness of Terlipressin on Modulation of Portal Vein Pressure after Hepatic Resections in Non-Cirrhotic Patients. A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Background-Objectives: It has been reported, that high posthepatectomy portal vein pressure (PVP) has deleterious effect on the liver parenchyma and causes posthepatectomy liver failure (PHLF) and increased 90-day mortality. Terlipressin, is widely used to mitigate the effects of portal hyper-tension. Randomised clinical trials (RCTs) demonstrated encouraging results of use of terlipressin for modulation of increased posthepatectomy PVP. The aim of the present study was to evaluate the effectiveness of the pharmacological modulation of the increased posthepatectomy PVP after major hepatectomy. Methods: Systematic literature searches of electronic databases in accordance with PRISMA was conducted. Meta-analysis was conducted using both fixed- and random-effects models. Results: Three randomised controlled trials (RCTs) comparing terlipressin versus placebo including 284 patients of pooled 60 studies were selected. Placebo cohort patients were significantly younger by 5 years compared to terlipressin cohort. However, the terlipressin cohort demonstrated significantly shorter intensive care unit (ICU) stay compared to placebo cohort. Conclusions: The first meta-analysis demonstrated that terlipressin cohort patients although significantly older by 5 years had significantly shorter ICU stay compared to placebo cohort. Furthermore, though statistically nonsignificant only 6% of terlipressin patients needed inotropic support compared to 16.4% of placebo cohort.

Study of anatomical variations of hepatic vasculature using multidetector computed tomography angiography.

PURPOSE: Preoperative evaluation of the hepatic vasculature is necessary to minimize mortality and morbidity during various surgeries due to the complexity of liver anatomy. The purpose of our investigation is to determine the anatomical variations in the hepatic vascular system by using multidetector computed tomography. METHODS: In this observational study, 500 patients aged between 1 and 86 years were randomly chosen from a patient population referred for computed tomography angiography for various clinical indications. Multidetector computed tomography angiography examinations were performed using a 128 detector scanner. The area from the lower thoracic spine to symphysis pubis level, with the patient in a supine position, was adopted as the field of view. The percentage of occurrence of each of the vascular variant was determined. RESULTS: Normal arterial anatomy [Type I] was seen in 306 patients [61.2%]. Replaced left hepatic artery from the left gastric artery was the most common variant in our study, which was seen in 57 patients [11.4%]. Classic hepatic venous anatomy was found in 261 [52.2%] patients. An accessory inferior right hepatic vein was found in 110 [22%] patients. A large early branch of segment VIII into middle hepatic vein was found in 157 patients [31.4%]. Extraparenchymal branching of the right anterior portal vein from the left portal vein was the most common anomaly found in 12 [2.4%] patients. CONCLUSIONS: Computed tomography angiography can be used in preoperative evaluation in various hepatobiliary surgeries and interventional procedures, which give a lot of information regarding parenchyma and vascular system.

Sevoflurane versus ketamine+diazepam anesthesia for assessing systemic and hepatic hemodynamics in rats with non-cirrhotic portal hypertension.

The selection of the anesthetic regime is a crucial component in many experimental animal studies. In rodent models of liver disease, the combination of ketamine and diazepam (KD), generally by the intramuscular (i.m.) route, has traditionally been the anesthesia of choice for the evaluation of systemic and hepatic hemodynamics but it presents several problems. Here, we compared the performance of inhalational sevoflurane (Sevo) against the KD combination as the anesthesia used for hemodynamic studies involving the measurement of portal pressure in normal rats (Ctrl) and rats with non-cirrhotic portal hypertension induced by partial portal vein ligation (PPVL). Compared with Ctrl rats, rats with PPVL presented characteristic alterations that were not influenced by the anesthetic regime, which included liver atrophy, splenomegaly, increased plasma fibrinogen, decreased alkaline phosphatase and glycemia, and frequent ascites. The use of the KD combination presented several disadvantages compared with the inhalational anesthesia with sevoflurane, including considerable mortality, a higher need of dose adjustments to maintain an optimal depth of anesthesia, increases of heart rate, and alteration of blood biochemical parameters such as the concentration of aspartate aminotransferase, lactate, and lactic dehydrogenase. Rats anesthetized with sevoflurane, on the other hand, presented lower respiratory rates. Importantly, the anesthetic regime did not influence the measurement of portal pressure either in Ctrl or PPVL rats, with the increase of portal pressure being similar in Sevo- and KD- anesthetized groups of PPVL rats compared with their respective control groups. Overall, our results suggest that anesthesia with sevoflurane is preferable to the combination of KD for performing systemic and hepatic hemodynamic studies in rats with non-cirrhotic portal hypertension.

Sorafenib treatment has the potential to downstage advanced hepatocellular carcinoma before liver resection.

Sorafenib is acknowledged as the standard therapy for advanced hepatocellular carcinoma (HCC) but in the clinical practice the treatment of these patients is extremely complex and needs to be personalized. New evidence suggests that surgical resection-based multimodal treatments may improve outcome in these patients. There is no strong evidence supporting the ability of sorafenib in downstage HCC before surgery. We presented a case of a 53-year-old man with well-compensated HCV-cirrhosis complicated with HCC and neoplastic portal vein thrombosis. The patient was treated initially with sorafenib with optimal radiological and serological response and subsequently with liver resection. Pathological examination showed necrotic portal thrombosis and massive necrosis of a metastatic regional node confirming radiological evidence. This finding suggests that sorafenib exhibits a potential to downstage advanced HCC which is not irrelevant. A possible combination of different modalities has to be considered in the view of a personalized medicine.

Nonselective ß-Blockers May Progress the Thrombosis of Portal Venous System in Cirrhotic Patients: A Retrospective Observational Study.

INTRODUCTION: Occlusive portal venous system thrombosis (PVT) is significantly associated with poor outcomes in cirrhotic patients. Nonselective ß-blockers (NSBBs) may be associated with the development of PVT. However, the role of NSBBs in progressing thrombosis remains unclear. METHODS: Forty-three patients on whom contrast-enhanced computed tomography or magnetic resonance imaging was performed twice, and for whom there was detailed information regarding NSBBs, were eligible in this study, including 16 in the NSBBs group and 27 in the no NSBBs group. A composite endpoint of progressing thrombosis included the development of PVT in patients without PVT and aggravation of PVT in patients with PVT. Logistic regression analysis was employed to identify the effect of NSBBs on the progression of PVT. RESULTS: At the last admission, 13 patients had progressing thrombosis. The incidence of progressing thrombosis was significantly higher in the NSBBs group than in the no NSBBs group [50.0% (8/16) vs. 18.5% (5/27), P = 0.030]. The use of NSBBs (odds ratio 4.400, 95% confidence interval 1.107-17.482, P = 0.035) was significantly associated with progressing thrombosis in univariate logistic regression analyses, but not significant (odds ratio 4.084, 95% confidence interval 0.488-34.158, P = 0.194) in multivariate logistic regression analyses. CONCLUSIONS: NSBBs may play a role in the progression of PVT in liver cirrhosis. The benefits and risks of NSBBs in the management of liver cirrhosis should be fully weighed.

Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis.

BACKGROUND: Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated. METHODS: Therefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein. RESULTS: While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001). CONCLUSIONS: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03584204.

The Anatomical Pattern of the Proximal Jejunal Vein as a Prognostic Factor in Patients With Pancreatic Head Cancer Treated With Preoperative Chemoradiation Therapy.

BACKGROUND/AIM: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC). PATIENTS AND METHODS: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed. RESULTS: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005). CONCLUSION: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival.

Transarterial Chemoembolization (TACE) Combined with Sorafenib in Treatment of HBV Background Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Propensity Score Matching Study.

OBJECTIVES: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains a challenge in management. Transarterial chemoembolization (TACE) has been used for patients with PVTT but efficiency was limited with a median overall survival of 4 to 6.1 months. The aim of this study is to evaluate the efficiency of TACE combined with sorafenib in HBV background HCC with PVTT. METHODS: A total of 498 patients were enrolled in the study including 69 patients who received TACE combined with sorafenib and 429 patients treated with TACE alone between January 1st, 2008, and April 30st, 2014. Using the 1:2 propensity score matching, 138 well-balanced patients were enrolled. Overall survival (OS) was compared between the two groups. The Kaplan-Meier method was used to evaluate the OS, and the differences between groups were analyzed with a log-rank test. RESULTS: TACE combined with sorafenib improved the OS of the patients compared with TACE alone (13.0 vs 6.0 months, p<0.001). After propensity score matching, the median OS of combination therapy and TACE were 13.0 and 7.0 months, respectively (p=0.001). Subgroup analysis revealed that the patients younger than 60 years old, male patients, AFP more than 400ng/ml, tumor size more than 5cm, or type III/IV PVTT had OS benefits from TACE combined with sorafenib. CONCLUSIONS: Compared with TACE therapy alone, TACE combined with sorafenib could improve OS in HBV background HCC patients with PVTT. The patients who are younger, male, or with more tumor burden may benefit more from combination therapy.

Successful intravenous administration of argatroban in the management of heparin-resistant and surgery-resistant mesenteric vein thrombosis.

A 78-year-old woman visited the emergency department with complaints of progressively worsening abdominal pain for a week. Nausea and vomiting started at the time of the visit. An abdominal contrast-enhanced CT (CECT) revealed a filling defect of portal vein, splenic vein and superior mesenteric vein (SMV) which was diagnosed as portal vein and mesenteric venous thrombosis (MVT). Intravenous administration of unfractionated heparin was initiated. However, her symptoms did not improve, and she underwent surgical thrombectomy on the second day of hospitalisation. On the sixth day, CECT revealed the recurrence of thrombi in the portal vein, SMV and along the central venous catheters. We switched heparin to argatroban on the eighth day. After administering argatroban, CECT revealed that the thrombi had almost disappeared by the 40th day. In this case, argatroban was considered effective for heparin-resistant and surgery-resistant portal vein and MVT.

CYP3A4 Induction in the Liver and Intestine of Pregnane X Receptor/CYP3A-Humanized Mice: Approaches by Mass Spectrometry Imaging and Portal Blood Analysis.

Induction of cytochrome P450 enzyme 3A (CYP3A) in response to pregnane X receptor (PXR) activators shows species-specific differences. To study the induction of human CYP3A in response to human PXR activators, we generated a double-humanized mouse model of PXR and CYP3A. CYP3A-humanized mice generated by using a mouse artificial chromosome (MAC) vector containing the entire genomic human CYP3A locus (hCYP3A-MAC mouse line) were bred with PXR-humanized mice in which the ligand-binding domain of mouse PXR was replaced with that of human PXR, resulting in double-humanized mice (hCYP3A-MAC/hPXR mouse line). Oral administration of the human PXR activator rifampicin increased hepatic expression of CYP3A4 mRNA and triazolam (TRZ) 1'- and 4-hydroxylation activities, CYP3A probe activities, in the liver and intestine microsomes of hCYP3A-MAC/hPXR mice. The plasma concentration of TRZ after oral dosing was significantly decreased by rifampicin treatment in hCYP3A-MAC/hPXR mice but not in hCYP3A-MAC mice. In addition, mass spectrometry imaging analysis showed that rifampicin treatment increased the formation of hydroxy TRZ in the intestine of hCYP3A-MAC/hPXR mice after oral dosing of TRZ. The plasma concentration of 1'- and 4-hydroxy TRZ in portal blood was also increased by rifampicin treatment in hCYP3A-MAC/hPXR mice. These results suggest that the hCYP3A-MAC/hPXR mouse line may be a useful model to predict human PXR-dependent induction of metabolism of CYP3A4 substrates in the liver and intestine. SIGNIFICANCE STATEMENT: We generated a double-humanized mouse line for CYP3A and PXR. Briefly, CYP3A-humanized mice generated by using a mouse artificial chromosome vector containing the entire genomic human CYP3A locus were bred with PXR-humanized mice in which the ligand-binding domain of mouse PXR was replaced with that of human PXR. Expression of CYP3A4 and metabolism of triazolam, a typical CYP3A substrate, in the liver of CYP3A/PXR-humanized mice were enhanced in response to rifampicin, a typical human PXR activator. Enhancement of triazolam metabolism in the intestine of CYP3A/PXR-humanized mice was firstly shown by combination of mass spectrometry imaging of sliced intestine and liquid chromatography with tandem mass spectrometry analysis of metabolite concentration in portal blood after oral dosing of triazolam.

Functionalized cerium oxide nanoparticles mitigate the oxidative stress and pro-inflammatory activity associated to the portal vein endothelium of cirrhotic rats.

BACKGROUND AND AIMS: The occurrence of endothelial alterations in the liver and in the splanchnic vasculature of cirrhotic patients and experimental models of liver diseases has been demonstrated. However, the pathological role of the portal vein endothelium in this clinical context is scarcely studied and, therefore, deserves attention. In this context, we aimed to investigate whether pathological endothelial activation occurs in the portal vein of cirrhotic rats. METHODS: Cirrhosis was induced in wistar rats by CCl4 inhalation. We generated immortalized endothelial cells from the portal vein of control (CT-iPVEC) and cirrhotic rats (CH-iPVEC) by retroviral transduction of the SV40 T antigen. We assessed differential gene expression and intracellular reactive oxygen species (ROS) levels in iPVECs and in portal veins of control and cirrhotic rats. Finally, we assessed the therapeutic effectiveness of cerium oxide nanoparticles (CeO2NP) on reversing PVEC activation and macrophage polarization. RESULTS: CH-iPVECs overexpressed collagen-I, endothelin-1, TIMP-1, TIMP-2, IL-6 and PlGF genes. These results were consistent with the differential expression showed by whole portal veins from cirrhotic rats. In addition, CH-iPVECs showed a significant increase in intracellular ROS and the capacity of potentiating M1 polarization in macrophages. The treatment of CH-iPVECs with CeO2NPs blocked intracellular ROS formation and IL-6 and TIMP-2 gene overexpression. In agreement with the in vitro results, the chronic treatment of cirrhotic rats with CeO2NPs also resulted in the blockade of both ROS formation and IL-6 gene overexpression in whole portal veins. CONCLUSIONS: Endothelial cells from portal vein of cirrhotic rats depicted an abnormal phenotype characterized by a differential gene expression and the induction of M1 polarization in macrophages. We identified the excess of intracellular reactive oxygen species (ROS) as a major contributor to this altered phenotype. In addition, we demonstrated the utility of the nanomaterial cerium oxide as an effective antioxidant capable of reverse some of these pathological features associated with the portal vein in the cirrhosis condition.

Effects of ajmaline on contraction patterns of isolated rat gastric antrum and portal vein smooth muscle strips and on neurogenic relaxations of gastric fundus.

Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause alterations in gastrointestinal motility. The effects of ajmaline on isolated gastric and portal vein smooth muscle and the underlying mechanisms are unknown. We studied the effects of ajmaline on the contractile patterns of isolated preparations of gastric antrum and portal vein from Wistar rats. The organ bath technique was used to measure spontaneous or pharmacologically induced isometric contractions. Changes in force observed after application of ajmaline or under control conditions are reported as % of the amplitude of an initial K+-induced contraction. Electric field stimulation was used to study neurogenic relaxations of gastric fundus smooth muscle. Ajmaline increased the amplitude of spontaneous contractions of muscle strips (portal vein: control 31.1 ± 15.2%, with 100 µM ajmaline 76.6 ± 32.3%, n = 9, p < 0.01; gastric antrum: control 9.5 ± 1.6%, with 100 µM ajmaline 63.9 ± 9.96%, n = 14, p < 0.01). The frequency of spontaneous activity was reduced in portal vein, but not in gastric antrum strips. The effects of ajmaline were not blocked by tetrodotoxin, L-nitroarginine methyl ester, or atropine. Ajmaline abolished coordinated neurogenic relaxations triggered by electric field stimulation and partly reversed the inhibition of GA spontaneous activity caused by the gap junction blocker carbenoxolone. Ajmaline enhances the amplitude of spontaneous contractions in rat gastric and portal vein smooth muscle. This effect may be accompanied, but not caused by an inhibition of enteric neurotransmission. Enhanced syncytial coupling as indicated by its ability to antagonize the effects of carbenoxolone is likely to underlie the enhancement of contractility.

Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study.

BACKGROUND: This study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT. METHODS: This retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification. RESULTS: In PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types. CONCLUSION: TACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.

Direct-Acting Oral Anticoagulants (DOACs) in Cirrhosis and Cirrhosis-Associated Portal Vein Thrombosis.

Direct-acting oral anticoagulants (DOACs) have provided benefit in patients requiring anticoagulation for certain diseases by decreasing the burden of subcutaneous injections and the requirement for frequent monitoring through regular blood tests, to ensure adequacy of the therapeutic doses. Studies have demonstrated DOACs to be as safe, and in some instance safer, compared with traditional anticoagulants in the general population. However, the studies evaluating DOACs excluded patients with cirrhosis, a condition associated with an increased risk of developing portal vein thrombosis (PVT). Warfarin or low-molecular weight heparin are the standard-of-care treatment for acute PVT in cirrhosis, although there is enthusiasm in a paradigm shift switching to DOACs for the treatment of acute PVT in cirrhosis, particularly since the release of DOAC antidotes. This article reviews the current Food and Drug Administration-approved DOACs, hepatic metabolism of DOACs, pharmacokinetics of DOACs in patients with cirrhosis, safety of DOACs (including bleeding, hepatotoxicity, and pregnancy), current treatment guidelines for PVT in cirrhosis, and studies evaluating the use of DOACs in cirrhosis and for the treatment of PVT in cirrhosis. The potential use of DOACs for PVT primary prophylaxis in at-risk patients with cirrhosis and the possible antifibrotic effects of DOACs are also discussed.

The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig.

Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis, and when PVP is reduced, rates of liver dysfunction decrease. The aim of the present study was to characterize the hemodynamic, biochemical, and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects. Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80% hepatectomy, and were maintained under terminal anesthesia for 8 h. The primary outcome was changed in PVP. Secondary outcomes included portal venous flow (PVF), hepatic arterial flow (HAF), and biochemical and histological markers of liver injury. Hepatectomy increased PVP (9.3 ± 0.4 mmHg pre-hepatectomy compared with 13.0 ± 0.8 mmHg post-hepatectomy, P<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g, P<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min, P=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg, P=0.046 and PCS = 8.3 ± 1.2 mmHg, P=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min, P<0.0001 and PCS = 488.4 ± 106.4 ml/min, P=0.002) compared with control. Treatment with terlipressin increased HAF (73.2 ± 11.3 ml/min) compared with control (40.3 ± 6.3 ml/min, P=0.026). The results of the present study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.

Intravascular and intraparenchymatous hepatic segmentary sclerosis.

PURPOSE: To evaluate the morphological effects of injected sclerosing agents into the liver. METHODS: This study was performed on twenty dogs, distributed into five groups: Group 1 (n = 5) - control, Group 2 (n = 5) - injection of 50% glucose solution inside hepatic parenchyma and animals followed during seven days, Group 3 (n = 10) - injection of ethanol inside hepatic parenchyma and animals distribution into two subgroups Subgroup 3A (n = 5) - followed during 24 hours and subgroup 3B (n = 5) - followed during seven days (group 3B), Group 4 (n = 5) - ethanol injection inside left portal vein branch and followed during 24 hours. Livers were macroscopically evaluated, submitted to hepatic arteriography and portography, then histology. RESULTS: All animals in Group 4 died within 23 hours due to diffuse hepatic necrosis. The animals of groups 2 and 3 had a satisfactory evolution. Fibrosis formed in the segment reached by the sclerosant solution and interruption of the contrast flow injected into the portal system. CONCLUSION: Intrahepatic parenchymal ethanol injection is well tolerated and causes sclerosis restricted to a specific segment; however, intraportal ethanol injection causes massive hepatic necrosis and can lead to death.