Liver volumetry and liver-regenerative interventions: history, rationale, and emerging tools.

BACKGROUND: Postoperative hepatic insufficiency (PHI) is the most feared complication after hepatectomy. Volume of the future liver remnant (FLR) is one objectively measurable indicator to identify patients at risk of PHI. In this review, we summarized the development and rationale for the use of liver volumetry and liver-regenerative interventions and highlighted emerging tools that could yield new advancements in liver volumetry. METHODS: A review of MEDLINE/PubMed, Embase, and Cochrane Library databases was conducted to identify literature related to liver volumetry. The references of relevant articles were reviewed to identify additional publications. RESULTS: Liver volumetry based on radiologic imaging was developed in the 1980s to identify patients at risk of PHI and later used in the 1990s to evaluate grafts for living donor living transplantation. The field evolved in the 2000s by the introduction of standardized FLR based on the hepatic metabolic demands and in the 2010s by the introduction of the degree of hypertrophy and kinetic growth rate as measures of the FLR regenerative and functional capacity. Several liver-regenerative interventions, most notably portal vein embolization, are used to increase resectability and reduce the risk of PHI. In parallel with the increase in automation and machine assistance to physicians, many semi- and fully automated tools are being developed to facilitate liver volumetry. CONCLUSION: Liver volumetry is the most reliable tool to detect patients at risk of PHI. Advances in imaging analysis technologies, newly developed functional measures, and liver-regenerative interventions have been improving our ability to perform safe hepatectomy.

Cambios fisiopatológicos y complicaciones de las resecciones hepáticas / Physiopathological changes and complications of liver resections / Alterações fisiopatológicas e complicações das ressecções hepáticas

Las modernas técnicas quirúrgicas y anestésicas han permitido ampliar el número de intervenciones quirúrgicas a nivel hepático por diversas patologías. Logrando disminuir su moralidad pero manteniendo al día de hoy elevados niveles de morbilidad. Durante la cirugía hepática se producen cambios hemodinámicos vinculados a la movilización del hígado, a los clampeos y a las pérdidas sanguíneas independientemente de la vía de abordaje. En el postoperatorio las complicaciones o cambios fisiopatológicos derivan de las lesiones producidas por los fenómenos de isquemia y reperfusión; y aquellas producidas por la regeneración hepática. Dicha capacidad depende no solo de la cantidad de hígado remanente sino también de la posible hepatopatía preexistente. La insuficiencia hepática postoperatoria es la complicación más temida y se manifiesta con ictericia, ascitis, encefalopatía y alteraciones en la paraclínica como la hiperbilirrubinemia y descenso del tiempo de protrombina. Las complicaciones quirúrgicas dependen del procedimiento realizado y se dividen principalmente en biliares y vasculares. Las secuelas de las hepatectomías dependen de factores como el estado general del paciente, la presencia hepatopatía, el acto quirúrgico y la cantidad y calidad del hígado remanente.

Modern surgical and anesthetic techniques have made it possible to increase the number of liver surgeries for various pathologies. This has reduced morbidity but still maintains high levels of morbidity. During hepatic surgery, hemodynamic changes related to liver mobilization, clamping and blood loss occur independently of the approach route. In the postoperative period, complications or pathophysiological changes derive from the lesions produced by ischemia and reperfusion phenomena; and those produced by hepatic regeneration. This capacity depends not only on the amount of remaining liver but also on the possible pre-existing hepatopathy. Postoperative liver failure is the most feared complication and manifests with jaundice, ascites, encephalopathy and paraclinical alterations such as hyperbilirubinemia and decreased prothrombin time. Surgical complications depend on the procedure performed and are mainly divided into biliary and vascular. The sequelae of hepatectomies depend on factors such as the patient's general condition, the presence of liver disease, the surgical procedure and the quantity and quality of the remaining liver.

As modernas técnicas cirúrgicas e anestésicas tornaram possível aumentar o número de cirurgias hepáticas para várias patologias. Isto levou a uma diminuição da morbidade, mas ainda mantém altos níveis de morbidade. Durante a cirurgia hepática, ocorrem alterações hemodinâmicas ligadas à mobilização hepática, pinçamento e perda de sangue, independentemente da via de aproximação. No período pós-operatório, complicações ou alterações fisiopatológicas derivam de lesões causadas por fenômenos de isquemia e reperfusão, e aquelas causadas pela regeneração hepática. Esta capacidade depende não apenas da quantidade de fígado restante, mas também de uma possível doença hepática pré-existente. A insuficiência hepática pós-operatória é a complicação mais temida e se manifesta com icterícia, ascite, encefalopatia e alterações paraclínicas, tais como hiperbilirrubinemia e diminuição do tempo de protrombina. As complicações cirúrgicas dependem do procedimento realizado e são divididas principalmente em biliares e vasculares. As seqüelas de hepatectomias dependem de fatores como o estado geral do paciente, a presença de doença hepática, o procedimento cirúrgico e a quantidade e qualidade do fígado restante.

Clinical outcomes of patients with hepatic insufficiency undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is currently a common treatment in high-risk aortic stenosis patients, but the impact of hepatic insufficiency on prognosis after TAVI is debatable and whether TAVI is superior to surgical aortic valve replacement (SAVR) in patients with hepatic insufficiency is uncertain. OBJECTIVE: To investigate the effect of abnormal liver function on the outcome and safety after TAVI and whether TAVI is superior to SAVR in patients with hepatic insufficiency. METHODS: PubMed, Embase, the Cochrane Library and Web of Science were systematically searched from inception up to 26 November 2021. Studies were eligible if mortality and complications after TAVI in patients with and without hepatic insufficiency, or mortality and complications for TAVI versus SAVR in patients with hepatic insufficiency were reported. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of each study. This meta-analysis was registered with PROSPERO (CRD42021253423) and was carried out by using RevMan 5.3 and Stata 14.0. RESULTS: This meta-analysis of 21 studies assessed a total of 222,694 patients. Hepatic insufficiency was associated with higher short-term (in-hospital or 30-day) mortality [OR = 1.62, 95% CI (1.18 to 2.21), P = 0.003] and 1-2 years mortality [HR = 1.64, 95% CI (1.42 to 1.89), P < 0.00001] after TAVI. Between TAVI and SAVR in patients with hepatic insufficiency, there was a statistically significant difference in in-hospital mortality [OR = 0.46, 95% CI (0.27 to 0.81), P = 0.007], the occurrence rate of blood transfusions [OR = 0.29, 95% CI (0.22 to 0.38), P < 0.00001] and the occurrence rate of acute kidney injury [OR = 0.55, 95% CI (0.33 to 0.91), P = 0.02]. CONCLUSIONS: TAVI patients with hepatic insufficiency may have negative impact both on short-term (in-hospital or 30-day) and 1-2-years mortality. For patients with hepatic insufficiency, TAVI could be a better option than SAVR.

[Is the alpps procedure justified in children?] / Opravdana li operatsiya alpps u detei?

The authors have analyzed the indications and outcomes after ALPPS procedure considering modern literature data devoted to this surgery in pediatric patients. No data on post-resection liver failure, as well as unclear future liver remnant function make it possible to question the feasibility of such procedures in children.

Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis.

BACKGROUND: To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy. METHODS: Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage. RESULTS: Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001). CONCLUSIONS: Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.

Prognostic Role of Hepatorenal Function Indexes in Patients With Ebstein Anomaly.

BACKGROUND: Hepatorenal dysfunction is a risk factor for mortality in patients with chronic tricuspid regurgitation due to acquired heart disease. Ebstein anomaly is the most common cause of primary tricuspid regurgitation in adults with congenital heart disease, but the prevalence and prognostic implications of hepatorenal dysfunction are unknown in this population. OBJECTIVES: The purpose of this study was to determine the risk factors and prognostic implications of hepatorenal dysfunction, as measured primarily by the use of model for end-stage liver disease excluding international normalized ratio (MELD-XI score), as well as looking at other associated factors. METHODS: This was a retrospective study of adults with Ebstein anomaly who received care at Mayo Clinic from 2003 to 2018. RESULTS: Of 692 patients, the median MELD-XI score was 10.2 (interquartile range: 9.4 to 13.3); 53 (8%) died and 3 (0.4%) underwent heart transplant. MELD-XI was an independent predictor of death/transplant (hazard ratio: 1.32; 95% confidence interval: 1.11 to 2.06; p < 0.001). In the subset of patients with serial MELD-XI scores (n = 416), temporal change in MELD-XI score (ΔMELD-XI) was also a predictor of death/transplant. In the subset of patients who underwent tricuspid valve surgery (n = 344), a post-operative improvement in MELD-XI score (ΔMELD-XI) was associated with improved long-term survival. Impaired right atrial (RA) reservoir strain and elevated estimated RA pressure were associated with worse baseline MELD-XI and ΔMELD-XI scores. CONCLUSIONS: Hepatorenal dysfunction is a predictor of mortality in Ebstein anomaly, and RA dysfunction and hypertension are hemodynamic biomarkers that can identify patients at risk for deterioration in hepatorenal function and mortality. These data highlight the prognostic importance of noncardiac organ-system dysfunction, and provide complementary clinical risk stratification metrics for management of these patients.

Obesity and metabolic outcomes in a safety-net health system.

In the United States, obesity has increased in prevalence over time and is strongly associated with subsequent outcomes such as diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). It is unclear, however, as to how the magnitude of NAFLD risk from obesity and DM is increased in safety-net health system settings. Among the San Francisco Health Network (SFHN) patients (N = 47,211), we examined the association between Body Mass Index (BMI) and elevated liver enzyme levels, including interaction by DM status. Our findings revealed that 32.2 percent of SFHN patients were obese, and Pacific Islanders in the safety-net had the highest rates of obesity compared to other racial groups, even after using higher race-specific BMI cutoffs. In SFHN, obesity was associated with elevated liver enzymes, with the relationship stronger among those without DM. Our findings highlight how obesity is a stronger factor of NAFLD in the absence of DM, suggesting that practitioners consider screening for NAFLD among safety-net patients with obesity even if DM has not developed. These results highlight the importance of directing efforts to reduce obesity in safety-net health systems and encourage researchers to further examine effect modification between health outcomes in such populations.

Liver damage at admission is an independent prognostic factor for COVID-19.

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.

Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease.

BACKGROUND AND AIMS: Hepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knock-in humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches. APPROACH AND RESULTS: SCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. Nuclear factor kappa B (NF-κB) activation in the liver of SCD mice inhibited farnesoid X receptor (FXR) signaling and its downstream targets, leading to loss of canalicular bile transport and altered bile acid pool. Intravital imaging revealed impaired bile secretion into the bile canaliculi, which was secondary to loss of canalicular bile transport and bile acid metabolism, leading to intrahepatic bile accumulation in SCD mouse liver. Blocking NF-κB activation rescued FXR signaling and partially ameliorated liver injury and sinusoidal ischemia in SCD mice. CONCLUSIONS: These findings identify that NF-κB/FXR-dependent impaired bile secretion promotes intrahepatic bile accumulation, which contributes to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of therapies to treat sickle cell hepatic crisis.

Biochemical recovery from exertional heat stroke follows a 16-day time course.

BACKGROUND: The aim of this study was to characterize the time-resolved progression of clinical laboratory disturbances days-following an exertional heat stroke (EHS). Currently, normalization of organ injury clinical biomarker values is the primary indicator of EHS recovery. However, an archetypical biochemical recovery profile following EHS has not been established. METHODS: We performed a retrospective analysis of EHS patient records in US military personnel from 2008-2014 using the Military Health System Data Repository (MDR). We focused on commonly reported clinical laboratory analytes measured on the day of injury and all proceeding follow-up visits. RESULTS: Over the prescribed period, there were 2,529 EHS episodes treated at 250 unique treatment locations. Laboratory results, including a standardized set of blood, serum and urine assays, were analyzed from 0-340 days following the initial injury. Indicators of acute kidney injury, including serum electrolyte disturbances and abnormal urinalysis findings, were most prevalent on the day of the injury but normalized within 24-48hours (creatinine, blood urea nitrogen, and blood and protein in urine). Muscle damage and liver function-associated markers peaked 0-4 days after injury and persisted outside their respective reference ranges for 2-16 days (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, myoglobin, prothrombin time). CONCLUSION: Biochemical recovery from EHS spans a 16-day time course, and markers of end-organ damage exhibit distinct patterns over this period. This analysis underscores the prognostic value of each clinical laboratory analyte and will assist in evaluating EHS patient presentation, injury severity and physiological recovery.

Indocyanine green clearance of remnant liver (ICG-Krem) predicts postoperative subclinical hepatic insufficiency after resection of colorectal liver metastasis: theoretical validation for safe expansion of Makuuchi's criteria.

BACKGROUND: Multidisciplinary treatment for colorectal liver metastases (CLMs) often includes major hepatectomy for preoperative chemotherapy-related hepatic injury, although the safety limit for resection extent is unclear. We investigated this parameter using the estimated indocyanine green clearance rate (ICG-K) of liver remnants, focusing on postoperative subclinical hepatic insufficiency (PHI). METHODS: Altogether, 225 patients who underwent resection of CLMs were studied. The predictive power of estimated ICG-K of liver remnant (ICG-Krem) for subclinical PHI (peak bilirubin ≥3 mg/dL or refractory ascites) was compared with those of other potential predictors. The suggested safety limit of ICG-Krem ≥0.05 was also assessed. RESULTS: Receiver-operating curve analysis revealed that ICG-Krem [area under the curve (AUC) 0.752, cutoff 0.102] was the best predictor of subclinical PHI (AUC range for others was 0.632-0.668). Makuuchi's criteria corresponded to ICG-Krem 0.10. Subclinical PHI incidence was significantly elevated at ICG-Krem <0.10 (26% vs 8%, p = 0.002), while potentially fatal PHI (peak bilirubin >7 mg/dL) was not observed until down to ICG-Krem of 0.05. CONCLUSIONS: ICG-Krem sensitively predicts subclinical PHI. Liver failure-related death could be avoided so long as ICG-Krem remains at ≥0.05. However, patients with ICG-Krem 0.05-0.10 are at high risk of subclinical PHI and require intensive care postoperatively.

[Meta-analysis of the outcomes of associating liver partition and portal vein ligation for staged hepatectomy versus portal vein embolization for the treatment of liver cancer with insufficient future liver remnant].

Objective: To explore the feasibility, safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) for the treatment of liver cancer with insufficient future liver remnant (FLR) . Methods: The data regarding the clinical controlled trials in comparison of ALPPS and PVE in liver surgery were collected from the both domestic and international publications searched through the datebases of PubMed, Cochrane Library, Embase, CNKI, and VIP.Meta analysis was performed by RevMan 5.3 software. Results: Total 10 studies with clinical control were analyzed (9 cohort studies and 1 randomized controlled study) .A total of 620 patients were included, with 165 cases in ALPPS group, 455 cases in PVE group.Results of Meta-analysis showed that there was statistically significant difference (P<0.05) between the two groups in the completion rate of two-steps surgery (OR=6.04, 95%CI: 2.97-12.31, Z=4.96) , FLR growth rate (MD=19.91, 95% CI: 8.64-31.18, Z=3.46) , two-steps surgical interval (MD=-30.48, 95%CI: -37.87--23.09, Z=8.09) , and R0 resection rate (OR=2.29, 95%CI=1.07-4.90, Z=2.13) .While there was no significant differences between the two groups in the mortality rate of postoperative within 90-days, postoperative the total complication rates, postoperative liver failure, and total hospital stay (all P>0.05) . Conclusions: Compared to the PVE procedures, ALPPS appears an effective treatment method for liver tumor with insufficient FLR.Therefore, the applications of ALPPS and PVE are limited and depending on further investigation.

Transient liver injury and severe neonatal cholestasis in infant with glucose-6-phosphate dehydrogenase deficiency due to a new mutation.

We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys¼ was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.

Gastrointestinal, Pancreatic, and Hepatic Manifestations of Cystic Fibrosis in the Newborn.

Gastrointestinal, pancreatic, and hepatic signs and symptoms represent the most common presentation of early disease among patients with cystic fibrosis and may be the initial indication of disease. Regardless of whether cystic fibrosis is diagnosed early by newborn screening or later by clinical course, the impact of gastrointestinal, pancreatic, and hepatic manifestations on early life is nearly ubiquitous. Conditions strongly linked with cystic fibrosis, such as meconium ileus and pancreatic insufficiency, must be recognized and treated early to optimize both short- and long-term care. Similarly, less specific conditions such as reflux, poor weight gain, and cholestasis are frequently encountered in infants with cystic fibrosis. In this population, these conditions may present unique challenges in which early interventions may have significant influence on both short- and long-term morbidity and mortality outcomes.

Association of multiple splanchnic venous thrombosis and left renal venous thrombosis, a rare complication of pancreatitis: a case report.

BACKGROUND: Vascular complications of acute pancreatitis are common. Splanchnic thrombosis accounts for 11% of these complications, whereas extrasplanchnic thrombosis remains a rare entity. These complications are associated with high morbidity and mortality. Diagnosis is established on the basis of clinical and radiological evaluation, especially computed tomography. Renal vein thrombosis has been reported previously, but only in association with thrombosis of the inferior vena cava. To our knowledge, renal vein thrombosis without inferior vena cava thrombosis has never been reported in the literature. We report a case of a woman who developed acute pancreatitis complicated with splanchnic thrombosis and renal vein thrombosis with a patent inferior vena cava. CASE PRESENTATION: A 48-year-old Moroccan woman with no significant past medical history presented to our emergency department with worsening epigastric pain and vomiting. Her physical examination was notable only for moderate epigastric tenderness. She was apyrexic and had no jaundice or any features of liver failure. An initial computed tomographic scan showed Balthazar grade C pancreatitis with multiple splanchnic thromboses involving the portal vein, superior mesenteric vein, and left renal vein and enteromesenteric venous infarct with no signs of bowel perforation. The inferior vena cava was patent. Therapeutic anticoagulation and analgesia were started with resumption of enteral feeding 72 h later. The result of a thrombophilia screen was negative. Two months later, the patient was admitted to the intensive care unit with acute liver failure. Computed tomography of the abdomen showed worsening ischemic liver lesions and no signs of bowel perforation. Biochemical analysis showed acute hepatitis with hepatocellular insufficiency. The clinical evolution was unfavorable, and the patient died 48 h later. CONCLUSIONS: Association of splanchnic and renal vein thrombosis without inferior vena cava thrombosis as a complication of acute pancreatitis has never been reported before. There are no specific aspects of management of this complication; therapeutic anticoagulation and symptomatic treatment are the main measures used owing to the lack of available organs for liver transplant. The prognosis depends on the consequences of splanchnic thrombosis and their complications.

Activation of Pregnane X Receptor Sensitizes Mice to Hemorrhagic Shock-Induced Liver Injury.

Hemorrhagic shock (HS) is a life-threatening condition associated with tissue hypoperfusion and often leads to injury of multiple organs including the liver. Pregnane X receptor (PXR) is a species-specific xenobiotic receptor that regulates the expression of drug-metabolizing enzymes (DMEs) such as the cytochrome P450 (CYP) 3A. Many clinical drugs, including those often prescribed to trauma patients, are known to activate PXR and induce CYP3A. The goal of this study is to determine whether PXR plays a role in the regulation of DMEs in the setting of HS and whether activation of PXR is beneficial or detrimental to HS-induced hepatic injury. PXR transgenic, knockout, and humanized mice were subject to HS, and the liver injury was assessed histologically and biochemically. The expression and/or activity of PXR and CYP3A were manipulated genetically or pharmacologically in order to determine their effects on HS-induced liver injury. Our results showed that genetic or pharmacological activation of PXR sensitized wild-type and hPXR/CYP3A4 humanized mice to HS-induced hepatic injury, whereas knockout of PXR protected mice from HS-induced liver injury. Mechanistically, the sensitizing effect of PXR activation was accounted for by PXR-responsive induction of CYP3A and increased oxidative stress in the liver. The sensitizing effect of PXR was attenuated by ablation or pharmacological inhibition of CYP3A, treatment with the antioxidant N-acetylcysteine amide, or treatment with a PXR antagonist. Conclusion: We have uncovered a function of PXR in HS-induced hepatic injury. Our results suggest that the unavoidable use of PXR-activating drugs in trauma patients has the potential to exacerbate HS-induced hepatic injury, which can be mitigated by the coadministration of antioxidative agents, CYP3A inhibitors, or PXR antagonists.

A novel liver retraction method in laparoscopic gastrectomy for gastric cancer.

BACKGROUND: Retracting the lateral liver segment during laparoscopic distal gastrectomy is important for achieving an optimal surgical field. However, excessive force may injure the liver, causing temporary abnormalities of liver function tests after laparoscopic surgery. We developed a new liver retraction method and assessed its safety and utility. PATIENTS AND METHODS: We retrospectively analyzed records in our surgical database of consecutive surgical patients who underwent laparoscopic distal gastrectomy for early gastric cancer. We divided the 229 patients into two groups based on the liver retraction method used, either flexible liver retraction with clipping and suturing (FLICS) or the Nathanson retractor (NR). One-to-one propensity score matching was performed to match patients, resulting in the records of 53 pairs of cases extracted from the database. Operative and postoperative outcomes were assessed, including following the values of serum liver enzymes, total bilirubin, and C-reactive protein until postoperative day 30. RESULTS: There were no significant differences in patient characteristics or preoperative data in the two groups. The retraction method was not changed intraoperatively for any patients. The operative time was significantly shorter in the FLICS group, but the amount of bleeding did not differ. Liver injury was not observed as a result of liver retraction during surgery. In both groups, serum liver enzymes temporarily increased after surgery but improved rapidly thereafter. The postoperative increases in aspartate transaminase, alanine transaminase, and C-reactive protein levels were significantly lower in the FLICS than in the NR group. No serious complications associated with liver retraction were observed in either group. CONCLUSIONS: Our new liver retraction technique provided an optimal surgical field without inducing liver dysfunction. It is a simple, safe, and effective liver retraction technique.

Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients.

BACKGROUND: Although recent advances in surgical techniques and perioperative management have reduced the morbidity and mortality after hepatectomy, hepatic insufficiency after major hepatectomy remains an important concern. This study aimed to clarify the risk factors for post-hepatectomy liver insufficiency. METHODS: We enrolled 103 consecutive patients who underwent major hepatectomy which was defined as resection of four or more segments. Hepatic insufficiency is defined as an increase in serum total bilirubin after hepatectomy of 7 mg/dL or more, or death from multiple organ failure. We compared the patient disposition, demographics, perioperative factors such as surgical method, combined procedure, morbidity and so on between the patients with or without hepatic insufficiency. RESULTS: Hepatic insufficiency occurred in 14 patients (14%) and six of them died during the hospital stay (6%). Risk factors by univariate analysis were the percentage of hepatic parenchyma to be resected (P = .025), combined procedure (P = .008) and postoperative morbidity excluding hepatic insufficiency (P < .001). A combined procedure (P = .036) and postoperative morbidity excluding hepatic insufficiency (P = .002) were a significant risk factor by multivariate analysis. CONCLUSION: Unless remaining liver after hepatectomy has enough volume, combined procedure may account for hepatic insufficiency, which can follow the development of postoperative morbidity.

Nuclear Factor (Erythroid-Derived 2)-Like 2 Regulates the Hepatoprotective Effects of Remote Ischemic Conditioning in Hemorrhagic Shock.

AIMS: Remote ischemic conditioning (RIC) protects against organ ischemia/reperfusion injury in experimental and clinical settings. We have demonstrated that RIC prevents liver and lung inflammation/injury after hemorrhagic shock/resuscitation (S/R). In this study, we used a murine model of S/R to investigate the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in mediating hepatoprotection. RESULTS: The combination of RIC with S/R caused a synergistic rise in Nrf2 and its translocation to the nucleus in the liver. Increased activation of Nrf2 by RIC augmented heme oxygenase-1 (HO-1) and autophagy and exerted hepatoprotection, concurrent with reductions in S/R-induced TNF-α (tumor necrosis factor alpha) and IL-6 (interleukin-6). In Nrf2 knockout (KO) animals, RIC did not exert hepatoprotection, and it failed to upregulate HO-1 and autophagy. Further, resuscitating wildtype (WT) animals with blood from donor WT animals undergoing RIC was hepatoprotective, but not in Nrf2 KO recipient animals. Interestingly, RIC blood from Nrf2 KO donor animals was also not protective when used to resuscitate WT animals, suggesting a role for Nrf2 both in the afferent arm of RIC where protective factors are generated and also in the efferent arm where organ protection is exerted. Finally, RIC plasma prevented oxidant-induced zebrafish mortality, but not in Nrf2a morpholino knockdown fish. INNOVATION: Activation of Nrf2 is an essential mechanism underlying the hepatoprotective effects of RIC. Nrf2 appears to play a role in the afferent limb of RIC protection, as its absence precludes the generation of the protective humoral factors induced by RIC. CONCLUSION: Our studies demonstrate the critical role of Nrf2 in the ability of RIC to prevent organ injury after S/R.