Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy.

BACKGROUND: The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. METHODS: Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. RESULTS: Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). CONCLUSION: In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.

Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance.

Radiofrequency ablation versus surgical resection for hepatocellular carcinoma within the Milan criteria: A study of 281 Western patients.

OBJECTIVES: The aim of this study was to compare survival between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within Milan criteria. METHODS: From January 2004 to December 2013 we consecutively and retrospectively included all patients with first occurrence of HCC within Milan criteria receiving SR or RFA as first-line treatment. The cumulative overall survival (OS) and disease-free survival (DFS) were compared after inverse probability weighting (including confounding factor). RESULTS: A total of 281 patients (RFA 178, SR 103) were enrolled. In multivariate Cox regression RFA and SR were not independent predictors of survival or recurrence. The respective weighted 5 years OS and DFS for patients with propensity scores between 0.1-0.9 in the SR and RFA groups were 54-33% and 60-16.9%, P = 0.695 and P = 0.426, respectively. Local tumour progression rate did not differ according to treatment (P = 0.523). Major complication rate was higher in the SR group, P = 0.001. Hospitalisation duration was lower in the RFA group (mean 2.19 days, range 2-7) than in the SR group (mean 10.2 days, range 3-30), P < 0.001. CONCLUSION: This large Western study has shown that OS and DFS did not differ after RFA (using mainly multipolar devices) and SR, for HCC within the Milan criteria in a European population, with a shorter hospitalisation time and a lower complication rate for RFA.

A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection.

BACKGROUND & AIMS: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is a challenge to determine a patient's prognosis. We aimed to identify new prognostic markers of patients with HCC treated by liver resection. METHODS: We collected 314 HCC samples from patients at Bordeaux (1998-2007) and Créteil (2003-2007) hospitals in France. We analyzed the gene expression patterns of the tumors and compared expression patterns with patient survival times. Using the coefficient and regression formula of the multivariate Cox model, we identified a "5-gene score" associated with survival times. This molecular score was then validated in 2 groups of patients from Europe and the United States (n = 213) and China (n = 221). RESULTS: The 5-gene score, based on combined expression level of HN1, RAN, RAMP3, KRT19, and TAF9, was associated with disease-specific survival times of 189 patients with resected HCC in Bordeaux (hazard ratio = 3.5; 95% confidence interval: 1.9-6.6; P < .0001). The association between the 5-gene score and disease-specific survival was validated in an independent cohort of 125 patients in Créteil (hazard ratio = 2.3; 95% confidence interval: 1.1-4.9; P < .0001). The 5-gene score more accurately predicted patient outcomes than gene expression signatures reported previously. In multivariate analyses, the 5-gene score was associated with disease-specific survival, independent of other clinical and pathology feature of HCC. Disease-specific survival was also predicted by combining data on microvascular invasion, the Barcelona Clinic Liver Cancer classification system, and the 5-gene score in a nomogram. The prognostic accuracy of the 5-gene score was further validated in European and US patients with hepatitis C, cirrhosis, and HCC (overall survival P = .002) and in Asian patients with HCC with hepatitis B (overall survival, P = .02). Combining the 5-gene score with the expression pattern of 186 genes in corresponding cirrhotic tissues increased its prognostic accuracy. CONCLUSIONS: The molecular 5-gene score is associated with outcomes of patients with HCC treated by resection in different clinical settings worldwide. This new biomarker should be tested in clinical trials to stratify patients in therapeutic decisions.

Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience.

UNLABELLED: We took advantage of the reported genotype/phenotype classification to analyze our surgical series of hepatocellular adenoma (HCA). The series without specific known etiologies included 128 cases (116 women). The number of nodules varies from single, <5, and >or=5 in 78, 38, and 12 cases, respectively. The resection was complete in 95 cases. We identified 46 HNF1alpha-inactivated HCAs (44 women), 63 inflammatory HCAs (IHCA, 53 women) of which nine were also beta-catenin-activated, and seven beta-catenin-activated HCAs (all women); six additional cases had no known phenotypic marker and six others could not be phenotypically analyzed. Twenty-three of 128 HCAs showed bleeding. No differences were observed in solitary or multiple tumors in terms of hemorrhagic manifestations between groups. In contrast, differences were observed between the two main groups. Steatosis (tumor), microadenomas (resected specimen), and additional benign nodules were more frequently observed in HNF1alpha-inactivated HCAs (P < 0.01) than in IHCAs. Body mass index > 25, peliosis (tumor), and steatosis in background liver were more frequent in IHCA (P < 0.01). After complete resection, new HCAs in the centimetric range were more frequently found during follow-up (>1 year) in HNF1alpha-inactivated HCA. After incomplete resection (HCA left in nonresected liver), the majority of HCA remained stable in the two main groups and even sometimes regressed. Six patients of 128 developed hepatocellular carcinoma (HCC) (all were beta-catenin-activated, whether inflammatory or not). CONCLUSION: There were noticeable clinical differences between HNF1alpha-inactivated HCA and IHCA; there was no increased risk of bleeding or HCC related to the number of HCAs; beta-catenin-activated HCAs are at higher risk of HCC. As a consequence, we believe that management of HCA needs to be adapted to the phenotype of these tumors.

Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia.

Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3). Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between -326 and -142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D-responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR.

Over-expression of glutamine synthase in focal nodular hyperplasia (part 1): early stages in the formation support the hypothesis of a focal hyper-arterialisation with venous (portal and hepatic) and biliary damage.

BACKGROUND: Most focal nodular hyperplasia (FNH) cases are diagnosed by chance. We studied a case of pre-FNH. We used glutamine synthase as an immunohistochemical marker for perivenous zones. RESULTS: Neither fibrotic scars nor hepatocytic nodules surrounded by fibrosis with a ductular reaction were observed in the sections studied. Most sections generally displayed preserved architecture. The glutamine synthase-positive hepatocyte areas were wider than those observed in non-tumoural surrounding liver, and they tended to extend outwards. Portal tracts bordering the nodule were more fibrotic, with an absence of portal veins and ducts and with arterial proliferation often in proximity with large draining veins; isolated arteries were present and hepatic veins were rare in the nodule. These features appeared prior to the identification of other major criteria characteristics of FNH, thus supporting the "hypothesis of Wanless". CONCLUSION: The findings confirm that in FNH there is a portal tract injury leading to local portal vein injury. This leads to a cascade of events, including arterial venous shunts, ductular reaction, and scar formation.

Unexpected discovery of 2 cases of hepatocyte nuclear factor 1alpha-mutated infracentimetic adenomatosis.

We present 2 cases of hepatocyte nuclear factor 1alpha (HNF1alpha)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.

Efforts to improve local control in rectal cancer compromise survival by the potential morbidity of optimal mesorectal excision.

BACKGROUND: The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. STUDY DESIGN: From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. RESULTS: Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p<0.001). CONCLUSIONS: After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.

Prognostic factors and longterm survival after hepatic resection for hepatocellular carcinoma originating from noncirrhotic liver.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing in the world, probably because of the high prevalence of infections by hepatitis B and C viruses. Despite numerous publications on hepatic resection, prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. STUDY DESIGN: One hundred eight consecutive patients with HCC in noncirrhotic liver have been treated by hepatic resection in the past 18 years in our center. Clinical, biologic, and histopathologic parameters of these patients were collected. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative morbidity and mortality rates were 23% and 6.5%, respectively. The 3- and 5-year disease-free and overall survival rates were 55% and 43%, and 43% and 29%, respectively. Blood transfusion, absence of tumor capsule, and daughter nodules were independently associated with overall survival. But the only risk factors for recurrence were blood transfusion, absence of tumor capsule, daughter nodules, and margin resection < 10 mm. CONCLUSIONS: In the treatment of HCC without cirrhosis, hepatectomy remains a safe and legitimate treatment, but longterm results are impaired by a high rate of early recurrence likely related to metastatic dissemination. Only histopathologic factors related to the tumor are predictive of recurrence and overall survival.

Multiple telangiectatic focal nodular hyperplasia: vascular abnormalities.

The aim of this study was to look for vascular abnormalities in the liver of patients with multiple telangiectatic focal nodular hyperplasia. Four patients, all women on oral contraceptives, were included in this study. In none of the cases was the diagnosis of multiple telangiectatic focal nodular hyperplasia made preoperatively. In the nodules, the pathological aspect was quite characteristic with dilated sinusoidal areas surrounding compact areas. Compact areas comprised portal tract-like structures with vessels, mainly thickened arteries, usually amidst an inflammatory reaction. A ductular reaction of varied intensity was present in three cases. The non-nodular liver was grossly normal. However, in rare areas, there were obvious or minor vascular abnormalities looking like minimal abnormalities seen inside telangiectatic nodules. These results seem to support the concept that multiple telangiectatic focal nodular hyperplasia is a non-specific reaction to focal ischemia induced by various mechanisms such as hepatic vein thrombosis induced, perhaps, by oral contraceptives.

Impact of microscopic hepatic lymph node involvement on survival after resection of colorectal liver metastasis.

BACKGROUND: Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. Only a few studies have investigated the impact of hepatic lymph node involvement on survival. The aim of this retrospective study was to assess microscopic hepatic lymph node involvement in resectable colorectal liver metastasis and outcomes in patients with such involvement. STUDY DESIGN: From January 1985 to December 2000, 156 patients underwent curative liver resection in association with systematic hepatic lymph node dissection for colorectal liver metastasis. A first analysis was performed to assess the association between hepatic lymph node metastasis and patients' characteristics. A second analysis assessed survival after resection of liver colorectal metastasis by using the Kaplan-Meier method. RESULTS: Twenty-three of the 156 patients (15%) had microscopically involved hepatic lymph nodes. No predictive factor of lymph node metastasis was identified. Multivariate analysis showed that lymph node metastasis, preoperative carcinoembryonic antigen level, number of metastases, and morbidity were factors influencing survival. The 3- and 5-year survival rates of patients with lymph node metastasis were 27% and 5%, respectively, compared with 56% and 43% without lymph node metastasis (p = 0.0001). CONCLUSIONS: During resection of liver colorectal metastasis, microscopic lymph node involvement occurred in 15% of the patients and was associated with a poor 5-year survival. Hepatic lymph node dissection should be performed systematically to select high-risk patients.

Detection of nodules in liver cirrhosis: spiral computed tomography or magnetic resonance imaging? A prospective study of 88 nodules in 34 patients.

Detection and characterization of all focal lesions in the liver are critical for screening patients with chronic liver disease. The aim of this prospective study was to investigate the accuracy of magnetic resonance imaging (MRI) and spiral computed tomography for the diagnosis of hepatic nodules in cirrhotic patients when compared with pathological findings of the explanted liver. From February 1997 to July 1999, 34 cirrhotic patients waiting for orthotopic liver transplantation (OLT) (mean age, 53.5 +/- 9.3 years; 24 males) were included. All patients had MRI and spiral computed tomography examinations, and findings were matched with the histological findings. Data analyses were made using the McNemar chi-square test. Mean time between radiological examination (MRI or spiral computed tomography) and OLT was 43.8 +/- 39 days. A total of 88 nodules were found in the 34 patients: 54 hepatocellular carcinoma (HCC) (mean size, 18 +/- 10 mm) in 21 patients, 22 dysplastic nodules (mean size, 10.7 +/- 4.3 mm) in 11 patients, and 12 macroregenerative nodules in 13 patients. Lesion-by-lesion analyses showed that sensitivity of MRI and spiral computed tomography for nodule, HCC or dysplastic nodule diagnosis was 44.3 and 31.8% (P = 0.02), 61.1 and 51.9% (P = 0.2), and 27.3 and 0% (P = 0.04), respectively. Patient-by-patient analyses showed no statistical difference between spiral computed tomography and MRI for nodule diagnosis. In conclusion, in patients with liver cirrhosis, MRI is more accurate than spiral computed tomography for the detection of liver nodules and dysplastic nodules. However, tumour size is always a restricting factor for these two techniques, which are unable to detect small HCC in more than 60% of cases.

Long-term functional results after sphincter-saving resection for rectal cancer.

INTRODUCTION: A number of patients suffer from gastrointestinal side effects following sphincter-saving resection of the rectum. The aim of this study was to assess frequency and risk factors of long-term gastrointestinal side effects after sphincter-saving resection for rectal cancer. PATIENTS AND METHODS: Between 1980 and 1997, among 209 patients treated for rectal cancer by rectal resection and sphincter conservation, 145 who were alive without recurrence or colostomy, responded to a questionnaire. There were 85 males and 60 females with a mean age of 64 Years; the follow-up was 5.4 Years. The functional result was considered good if the number of stools per 24h was three or less with normal continence and poor if the number of stools was four or more or if fecal incontinence was present. Influence of age, gender, anastomotic height, type of sutured colon, colonic pouch, defunctioning stoma, leakage, stenosis, radiotherapy, history of irritable bowel syndrome and follow-up were analyzed. RESULTS: The mean anastomotic height was 5 cm from the anal margin. Functional results were good in 56% of patients and poor in 44%. Univariate analysis showed three variables to be significantly associated with the functional results: anastomotic height (P=0.001), radiotherapy (P=0.03) and follow-up > 24 Months (P=0.009). Multivariate analysis showed that only anastomotic height independently influenced functional results. They were good in 76%, 53% and 35% of patients for anastomoses located above 6 cm, between 6 and 3 cm, and below 3 cm from the anal margin, respectively. CONCLUSION: After sphincter-saving resection for rectal cancer, about half of patients have poor long-term functional results, the latter being related only to the anastomotic height. This suggests the need to preserve a small part of the rectum when oncologically feasible.

Pathological Diagnosis of Hepatocellular Cellular Adenoma according to the Clinical Context.

In Europe and North America, hepatocellular adenomas (HCA) occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis). When nodules are multiple, they are usually of the same subtype. HNF1 α -inactivated HCA occur almost exclusively in woman. The most important point of the classification is the identification of ß -catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage.

A second liver resection due to recurrent colorectal liver metastases.

BACKGROUND: Repeat liver resection because of recurrent colorectal liver metastases can provide survival benefit with a low rate of complications. DESIGN: Retrospective study. PARTICIPANTS: Forty patients who underwent a second hepatectomy because of liver metastases from colorectal cancer. MAIN OUTCOME MEASURES: Short- and long-term results of a second hepatectomy and determination of prognostic factors. RESULTS: The postoperative mortality rate was 2.5%. The postoperative morbidity rate was not significantly different after a second hepatectomy compared with single hepatectomy (42.5% and 27.5%, respectively; P = .10). Transfusion requirement and hospital stay were comparable for both a single and a second hepatectomy. Three- and 5-year overall survival rates were 55% and 31%, respectively. Disease-free survival rates at 3 and 5 years were, respectively, 49% and 27%. The interval between first and second hepatectomies and the presence of extrahepatic disease were independently related to survival (multivariate analysis). CONCLUSIONS: A second liver resection because of recurrent liver metastases from colorectal cancer is safe and provides a survival benefit similar to that with single hepatectomy. Our analysis suggests that the benefit of treatment is limited in patients who undergo a second hepatectomy within 1 year of the first operation and in those with extrahepatic disease.

Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry.

UNLABELLED: Hepatocellular adenomas (HCA) with activated beta-catenin present a high risk of malignant transformation. To permit robust routine diagnosis to allow for HCA subtype classification, we searched new useful markers. We analyzed the expression of candidate genes by quantitative reverse transcription polymerase chain reaction QRT-PCR followed by immunohistochemistry to validate their specificity and sensitivity according to hepatocyte nuclear factor 1 alpha (HNF1alpha) and beta-catenin mutations as well as inflammatory phenotype. Quantitative RT-PCR showed that FABP1 (liver fatty acid binding protein) and UGT2B7 were downregulated in HNF1alpha-inactivated HCA (P