Predictive value of perfusion CT for blood loss in liver resection.

Blood loss is associated with the degree of damage in liver stiffness. Severe liver steatosis is a matter of concern in liver surgery, but does not correlate with liver stiffness. This study aimed to assess the relationship between blood perfusion of the liver and blood loss in liver pathologies. Data from elective liver resection for liver cancer were analyzed. All patients underwent preoperative assessments including perfusion CT. Patients were divided into 4 groups in accordance with the pathological background of liver parenchyma. Relationships between portal flow as assessed by perfusion CT and perioperative variables were compared. Factors correlating with blood loss were analyzed. In 166 patients, portal flow from perfusion CT correlated positively with platelet count and negatively with indocyanine green retention rate at 15 min. Background liver pathology was normal liver (NL) in 43 cases, chronic hepatitis (CH) in 56, liver cirrhosis (LC) in 42, and liver steatosis (LS) in 25. Rates of hepatitis viral infection and pathological hepatocellular carcinoma were more frequent in LC and CH groups than in the other groups (p < 0.05). LC and LS showed significantly worse liver function than the NL and CH groups. Portal flow from perfusion CT correlated positively with damage to liver parenchyma and negatively with blood loss at liver transection. Low portal flow on perfusion CT predicts blood loss during liver transection.

Risk of colorectal cancer in chronic liver diseases: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of colorectal cancer (CRC) in various chronic liver diseases compared with the general population remains unclear. We performed a systematic review and meta-analysis to assess the risk of CRC in patients with chronic liver diseases before and after liver transplantation. METHODS: Electronic databases were searched for studies assessing the risk of CRC in patients with chronic liver diseases. The primary outcome was the pooled risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS: Fifty studies that included 55,991 patients were identified. Among studies that included hepatitis and cirrhotic patients, the pooled SIR was 2.06 (P < .0001; 95% confidence interval (CI), 1.46-2.90) with moderate heterogeneity (I2 = 49.2%), which appeared to be because of the difference between subgroup of diseases and the power of studies. Three studies reported an increased risk of CRC in primary sclerosing cholangitis patients (pooled SIR 6.70; P < .0001; 95% CI, 3.48-12.91) with moderate heterogeneity (I2 = 36.3%), which appeared to be because of the difference between the power of studies. Among studies that included post-transplant patients, the pooled SIR was 2.16 (P < .0001; 95% CI, 1.59-2.94) with moderate heterogeneity (I2 = 56.4%). Meta-regression showed a correlation between the proportion of autoimmune-related liver diseases and the risk of CRC. CONCLUSIONS: Patients with chronic liver diseases had an increased risk of CRC compared with the general population, which persisted after liver transplantation. A more intensive surveillance for CRC is warranted in this population.

Hepatopulmonary Syndrome: A Brief Review.

Hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease characterized by arterial hypoxemia. Mechanisms related to this event are diffusion-perfusion flaw, ventilation-perfusion (V/Q) mismatch, and direct arteriovenous shunts. Diagnosis of HPS is based on the presence of liver disease or portal hypertension, increased alveolar-arterial (A-a) PO2, and intrapulmonary vascular dilatations (IPVD). Lung transplantation (LT) remains the most effective therapy for HPS. In spite of its poor prognosis, we could improve the quality of life and survival rate of patients.

Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.

Resection of hepatocellular carcinoma (HCC) tumors by partial hepatectomy (PHx) is associated with promoting hepatocarcinogenesis. We have previously reported that PHx promotes hepatocarcinogenesis in the Mdr2-knockout (Mdr2-KO) mouse, a model for inflammation-mediated HCC. Now, to explore the molecular mechanisms underlying the tumor-promoting effect of PHx, we compared genomic and transcriptomic profiles of HCC tumors developing in the Mdr2-KO mice either spontaneously or following PHx. PHx accelerated HCC development in these mice by four months. PHx-induced tumors had major chromosomal aberrations: all were amplifications affecting multiple chromosomes. Most of these amplifications were located near the acrocentric centromeres of murine chromosomes. Four different chromosomal regions were amplified each in at least three tumors. The human orthologs of these common amplified regions are known to be amplified in HCC. All tumors of untreated mice had chromosomal aberrations, including both deletions and amplifications. Amplifications in spontaneous tumors affected fewer chromosomes and were not located preferentially at the chromosomal edges. Comparison of gene expression profiles revealed a significantly enriched expression of oncogenes, chromosomal instability markers and E2F1 targets in the post-PHx compared to spontaneous tumors. Both tumor groups shared the same frequent amplification at chromosome 18. Here, we revealed that one of the regulatory genes encoded by this amplified region, Crem, was over-expressed in the nuclei of murine and human HCC cells in vivo, and that it stimulated proliferation of human HCC cells in vitro. Our results demonstrate that PHx of a chronically inflamed liver directed tumor development to a discrete pathway characterized by amplification of specific chromosomal regions and expression of specific tumor-promoting genes. Crem is a new candidate HCC oncogene frequently amplified in this model and frequently over-expressed in human HCC.

Prediction of portal pressure from intraoperative ultrasonography.

BACKGROUND: Portal hypertension is a major risk factor for hepatic failure or bleeding in patients who have undergone hepatectomy, but it cannot be measured indirectly. We attempted to evaluate the intraoperative ultrasonography parameters that correlate with portal pressure (PP) in patients undergoing hepatectomy. METHODS: We examined 30 patients in whom PP was directly measured during surgery. The background liver conditions included chronic viral liver disease in seven patients, chemotherapy-associated steatohepatitis in four patients, fatty liver in one patient, hepatolithiasis in one patient, obstructive jaundice in one patient, and a normal liver in 16 patients. A multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for PP. RESULTS: The mean PP was 10.4 ± 4.1 mm Hg. The PP tended to be increased in patients with chronic viral hepatitis. A univariate analysis identified the association of the six following parameters with PP: the platelet count and the maximum (max), minimum (min), endo-diastolic, peak-systolic, and mean velocity in the portal vein (PV) flow. Using multiple linear regression analysis, the predictive formula using the PV max and min was as follows: Y (estimated PP) = 18.235-0.120 × (PV max.[m/s])-0.364 × (PV min). The calculated PP (10.44 ± 2.61 mm Hg) was nearly the same as the actual PP (10.43 ± 4.07 mm Hg). However, there was no significant relationship between the calculated PP and the intraoperative blood loss and post hepatectomy morbidity. CONCLUSIONS: This formula, which uses ultrasonographic Doppler flow parameters, appears to be useful for predicting PP.

Highest intraoperative lactate level could predict postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease.

BACKGROUND: The Pringle maneuver is used to minimize blood loss during liver transection; however, it may cause reperfusion injury, which can cause increased intraoperative lactate levels and an immune compromised state. This may further lead to infectious complications. METHODS: Here, we divided 77 patients who underwent hepatectomy between December 2007 and August 2010 into two groups: the chronic hepatitis and liver cirrhosis (CH + LC) group and normal liver (NL) group. We investigated the effect of the highest intraoperative lactate level on occurrence of infectious complications after hepatectomy by assessing the correlations of the highest intraoperative lactate level with total Pringle time, operative factors, and various parameters in serum after surgery. Parameters showing significant correlations with postoperative complications of Clavien-Dindo grade III or higher, with a wound or intra-abdominal infection, were analyzed by using interactive dot diagrams to determine cut-off values with the highest sensitivity and specificity. RESULTS: We noted that, to prevent postoperative infectious complications, the highest lactate level during liver resection should be maintained at <44.0 mg/dL in the NL group and <29.0 mg/dL in the CH + LC group. CONCLUSIONS: Minimizing the highest intraoperative lactate level may be important to prevent increase in postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease.

Assessment of preoperative exercise capacity in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy.

BACKGROUND: Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy. METHODS: Sixty-one HCC patients underwent preoperative cardiopulmonary exercise testing to determine their anaerobic threshold (AT). The AT was defined as the break point between carbon dioxide production and oxygen consumption per unit of time (VO2). Postoperative events including recurrence of HCC, death, liver failure, and complications of cirrhosis were recorded. Univariate and multivariate analyses were performed to evaluate associations between 35 clinical factors and outcomes, and identify independent prognostic indicators of event-free survival and maintenance of Child-Pugh class. RESULTS: Multivariate analyses identified preoperative branched-chain amino acid/tyrosine ratio (BTR) <5, alanine aminotransferase level ≥42 IU/l, and AT VO2 <11.5 ml/min/kg as independent prognostic indicators of event-free survival. AT VO2 <11.5 ml/min/kg and BTR <5 were identified as independent prognostic indicators of maintenance of Child-Pugh class. CONCLUSIONS: This study identified preoperative exercise capacity as an independent prognostic indicator of event-free survival and maintenance of Child-Pugh class in HCC patients with chronic liver injury undergoing hepatectomy.

Functional liver reserve parameters predictive for posthepatectomy complications.

BACKGROUND: Posthepatectomy complications have markedly decreased with advances in techniques and management; however, surgical risk to patients with injured livers is still not negligible. We evaluated several preoperative parameters of functional liver reserve tests in patients with various liver diseases as predictors of posthepatectomy complications. A comprehensive evaluation of preoperative liver functions is necessary for the prediction of the risk of posthepatectomy complications. METHODS: Over a 10-y period, we examined 442 patients who underwent hepatectomy for liver and biliary diseases. The patients' background liver diseases included chronic viral liver diseases in 211 patients, obstructive jaundice in 29 patients, and normal liver in 202 patients. Hepatectomy-related postoperative complications (i.e., long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 115 (26%) patients. A multivariate logistic analysis was performed to detect the predictive parameters, and a multivariate linear regression analysis was performed to derive a predictive formula for complications. RESULTS: A univariate analysis identified 15 significant parameters associated with hepatectomy-related complications, and eight parameters (i.e., presence of chronic hepatic injury, clearance index by technetium-99 m galactosyl human serum albumin liver scintigraphy of ≥ 0.60, total bilirubin level of >1 mg/dL, serum hyaluronic acid level of ≥ 75 ng/mL, major hepatectomy, blood loss of ≥ 950 mL, operating time of ≥ 500 min, and combined resection of another organ or major vessel) were independent predictive factors identified in the multivariate analysis. Clearance index by technetium-99 m galactosyl human serum albumin liver, bilirubin level, hyaluronic acid level, and major hepatectomy were the parameters included in the predictive formula. CONCLUSIONS: In the present study, we present a comprehensive formula based on the predictive parameters for hepatic complications for prospective assessment to avoid posthepatectomy morbidity.

Characterization of HCV-specific CD4+Th17 immunity in recurrent hepatitis C-induced liver allograft fibrosis.

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV-specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1ß, IL-6, IL-8 and MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1ß and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.

Effects of intermittent Pringle's manoeuvre on cirrhotic compared with normal liver.

BACKGROUND: Although patients with liver cirrhosis are supposed to tolerate ischaemia-reperfusion poorly, the exact impact of intermittent inflow clamping during hepatic resection of cirrhotic compared with normal liver remains unclear. METHODS: Intermittent Pringle's manoeuvre was applied during minor hepatectomy in 172 patients with a normal liver, 59 with chronic hepatitis and 97 with liver cirrhosis. To assess hepatic injury, delta (D)-aspartate aminotransferase (AST) and D-alanine aminotransferase (ALT) (maximum level minus preoperative level) were calculated. To evaluate postoperative liver function, postoperative levels of total bilirubin, albumin and cholinesterase (ChE), and prothrombin time were measured. RESULTS: Significant correlations between D-AST or D-ALT and clamping time were found in each group. The regression coefficients of the regression lines for D-AST and D-ALT in patients with normal liver were significantly higher than those in patients with cirrhotic liver. Irrespective of whether clamping time was 45 min or less, or at least 60 min, D-AST and D-ALT were significantly lower in patients with cirrhosis than in those with a normal liver. Parameters of hepatic functional reserve, such as total bilirubin, prothrombin time, albumin and ChE, were impaired significantly after surgery in patients with a cirrhotic liver. CONCLUSION: Patients with liver cirrhosis had a smaller increase in aminotransferase levels following portal triad clamping than those with a normal liver. However, hepatic functional reserve in those with a cirrhotic liver seemed to be affected more after intermittent inflow occlusion.

Chronic hepatitis E in liver transplant recipients: a significant clinical problem?

Hepatitis E is an inflammatory liver disease caused by infection with the hepatitis E virus (HEV). Five different HEV genotypes have been described. While HEV genotypes 1 and 2 primarily infect man, genotypes 3 and 4 have been detected both in humans and several animal species including pigs. HEV genotype 1 and 2 infections are frequent in Southern Asia and Africa. However, Hepatitis E is more and more considered as an re-emerging zoonotic disease also in industrialized countries as HEV genotype 3 infections seem to increase in Western Europe and North America. Acute hepatitis E usually takes an acute self limited course but may take a fulminant course in particular in pregnant women and patients with pre-existing chronic liver disease. Several cases of persistent HEV-infection have been reported in immunosuppressed patients during the last three years being associated with progressive liver disease in some patients. Thus, screening for HEV RNA should be part of the diagnostic work-up of elevated liver transaminases in organ transplantation recipients or HIV-infected individuals. In this review we summarize the recent data on hepatitis E with a particular focus on the importance of persistent HEV infections in liver transplant recipients.

[Left-side venous anastomosis as a method correcting blood outflow from the kidney].

Case histories and surgical protocols of 50 patients who were treated for chronic hepatitis by creating left-side renoportal venous anastomosis (RPVA) were analysed retrospectively. Early after surgery 75% patients had microhematuria, proteinuria to 0.033-0.066 g/l, leucocyturia. At discharge from the hospital these abnormalities were not registered in the majority of the patients. Three months after operation these indices were at the preoperative level. Significant shifts in parameters of urine were associated with an anomalous condition of the left renal vein (annular, retroaortal), its compression, portal hypertension and creation of RPVA without legation of the splenic vein. In a cositive compression test RPVA was created without arrest of arterial inflow for 45 min. This can be a criterion of feasibility of left renal vein ligature if left-side RPVA cannot be performed for preservation of the left kidney. Validity of left-side RPVA use for correction of blood outflow from the left kidney is proven by functional improvement and normal side of the kidneys in long-term postoperative follow-up.

Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

Long-term results of liver transplant in patients with chronic viral hepatitis-related liver disease in Singapore.

INTRODUCTION: Liver disease from chronic hepatitis B (CHB) and C (CHC) constitutes 57 percent of adult liver transplant in Singapore. Their long-term results post-transplant may be affected by recurrence of the viral illness. This study aims to evaluate the long-term results and survival in patients transplanted for CHB- and CHC-related liver disease. METHODS: Patients transplanted for CHB- and CHC-related disease from 1990 until March 2004, which included decompensated cirrhosis and hepatocellular carcinoma (HCC), were reviewed and analysed. RESULTS: 25 patients were transplanted for CHB-related liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year survival rates were 75 percent and 69 percent, respectively. Hepatitis B recurrence from YMDD mutants occurred in five patients, and four were treated successfully with adefovir dipivoxil, with resolution in transaminases and/or improvement in histology. One patient became non-compliant with follow-up and medications, and died 173 weeks post-transplant from reactivation of the wild-type hepatitis B virus. Nine patients were transplanted for CHC-related liver disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival rates of 89 percent and 76 percent, respectively. Two patients developed hepatitis C recurrence and were treated with interferon and ribavarin. One responded with sustained response but the other remained viraemic and died of HCC recurrence two years post-transplant. CONCLUSION: Long-term results from CHB- and CHC-related liver diseases were satisfactory and comparable to major transplant centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is controllable with current antiviral therapy.

Outcome using hemihepatic vascular occlusion versus the pringle maneuver in resections limited to one hepatic section or less.

Consensus is lacking concerning how to manage afferent vessels during hepatectomy, particularly as to the Pringle maneuver vs. selective hemihepatic clamping. Data for 81 hepatocellular carcinoma patients with chronic hepatitis or liver cirrhosis whose liver resection was limited to one section or less, including intraoperative data and postoperative liver function data, were analyzed retrospectively to compare two strategies. No significant differences of intraoperative data or postoperative clinical course were seen between the two groups, even in patients with chronic hepatitis or liver cirrhosis whose postoperative deterioration of liver function could be expected to be more than patients with a normal liver. The difference was evident only in serum alanine aminotransferase level on postoperative day 10 (mean +/- SEM, 64.5 +/- 5.1 IU in the Pringle group vs. 51.6 +/- 4.4 IU in the selective clamping group; P < 0.05). During liver resection limited to one section or less, even with underlying chronic hepatitis or cirrhosis, intermittent use of the Pringle maneuver preserved liver function to the same extent as selective clamping.

[Acute cholecystitis in combination with chronic hepatitis and cirrhosis of the liver].

An analysis of surgical treatment of cholelithiasis, acute cholecystitis was made which had appeared in 107 patients against the background of chronic diseases of the liver. Current diagnostic methods were used for differential diagnostics of jaundice: USI, CT, retrograde cholecystopancreatography, duodenoscopy. All the patients were operated upon against the background of hepatotropic and anti-ulcer therapy being performed. The main component of anesthesia during operation in most patients was epidural blockade which unlike multicomponent anesthesia had no negative effects on the indices of bilirubin in blood and aminotranspherase activity. Cholecystectomy, sanitation and decompression of bile ducts in patients with acute cholecystitis which appeared against the background of chronic lesion of the liver allowed to eliminate the source of portal toxemia, liquidate the mechanical source of cholestasis that, as a rule, results in liquidation of acute hepatic failure. The optimal method of differential diagnostics of jaundices was intraoperative cholangiography and choledochotomy.

Outcomes of liver transplantation for cryptogenic cirrhosis: a single-center study of 71 patients.

UNLABELLED: Cryptogenic cirrhosis (CC) is emerging as an important indication for orthotoptic liver transplantation (OLT) in the United States. Our aim was to identify risk factors associated with nonalcoholic steatohepatitis (NASH) in patients with CC and to evaluate outcomes following OLT. PATIENTS AND METHODS: A chart review was performed on patients transplanted for CC at the University of Nebraska Medical Center between October 1993 and May 2003. RESULTS: Seventy-one patients were identified (37 were men and 34 women). Average age was 53.5 years. Mean cholesterol and triglyceride levels increased from 174.8 to 222.3 mg/dL (P <.05) and from 162.60 to 279.66 mg/dL (P <.05), respectively. The prevalence of diabetes mellitus also increased from 37.14% to 54.93% (P <.05). Incidental hepatocellular carcinoma was present in six patients and high-grade dysplasia in one patient. Steatohepatitis developed in eight patients and recurrent cryptogenic disease in four, of whom one required retransplantation for decompensated liver disease. Rejection occurred in 24 patients. Cumulative incidence of graft failure at 1 year was 4% (95% CI 0% to 10%) and at 5 years was 7% (95% CI 0% to 18%). Survival at 1 year was 85% (95% CI 77% to 94%) and at 5 years was 73% (95% CI between 61% to 86%). CONCLUSIONS: Cryptogenic liver disease is an important cause of decompensated cirrhosis; NASH appears to be an intermediate stage in the development of this disease in a subset of patients. Short-term and 5-year survival rates in this series appear comparable to other liver transplant recipients, supporting liver transplantation as an acceptable treatment for CC.