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S1888 Small Intestinal Bacterial Overgrowth as a Predictive Factor for Development of Diarrhea in HCC Patients Treated With Sorafenib
AASLD Abstracts
evaluated the outcome of combined transarterial chemoembolization (TACE) and percutaneous local ablation therapy in patients with advanced HCC. (Patient and methods) This study was conducted in 212 patients between January 1995 and December 2008 at Yokohama City University Hospital, Japan. We evaluated the combined therapy with TACE-alone or RFA- / PEI-alone in terms of the survival and recurrence rates, in each of 3 subgroups, as follows I: exceeding the Milan criteria, combined therapy (n=35) vs. TACE-alone (n=30), II: 2.5-5.0cm, single lesion, combined therapy (n=47) vs. RFA- / PEI-alone (n=16), III: within 3.0cm, 2-3 lesions, combined therapy (n=64) vs. RFA- / PEI-alone (n=20). (Results) In subgroup I, both the overall survival rate (OS) and the median survival time (MST) were significantly superior in the combined therapy group than in the TACE-alone group (OS: 1-, 3-, 5- and 7-year = 100% 52%, 33% and 25% vs. 84%, 26%, 0% and 0%, respectively, p=0.007, MST: 36 months vs. 21 months, p=0.013). In subgroup II, both the OS and local recurrence rate tended to be superior in the combined therapy group as compared with the values in the RFA- / PEI-alone group (OS: 1-, 3-, 5-, and 7-year = 98%, 67%, 55% and 38% vs. 93%, 58%, 38% and 13%, respectively, p=0.065, local recurrence rate: 1-, 3-, and 5-year = 4%, 19% and 19% vs. 7%, 33% and 33%, respectively, p=0.178). In subgroup III, both the OS and distant intra-hepatic recurrence rate tended to be superior in the combined therapy group than in the RFA- / PEI-alone group (OS: 1-, 3-, 5-, and 7-year = 97%, 72%, 54% and 27% vs. 100%, 80%, 27% and 0% respectively, p=0.105, distant intrahepatic recurrence rate: 1-, 3-, and 5-year = 4%, 51% and 70% vs. 13%, 65% and 82%, respectively, p=0.108). The influence of deterioration of hepatic function in the combined therapy group, TACE-alone group, and the RFA- / PEI-alone group were similar. (Conclusion) Combined TACE and RFA / PEI therapy was more effective than TACE alone in cases exceeding the Milan criteria, and more effective than RFA / PEI alone in cases with a single, large HCC or multiple HCCs fulfilling the Milan criteria. This study suggested that combined therapy may be the most effective strategy for advanced HCC.
mice decreased compared with WT mice at 48 hours after PH. Knockout of SULF2 decreased the expression of CyclinD1 at 36 and 48 hours. On the other hand, the levels of serum ALT in SULF2 KO mice were higher than in WT mice at 3 and 6 hours and the number of TUNEL positive cells in SULF2 KO mice was higher at day 3 after PH. The phosphorylation of EGFR in SULF2 KO mice decreased at 3 and 6 hours after PH. The level of serum IL-6 in mice lacking SULF2 increased at 3 hours after PH. Conclusions: The absence of SULF2 impairs liver regeneration and increased liver damage and apoptosis after PH. Our results suggest that SULF2 plays a role in liver regeneration by modulating EGFR signaling and has a hepatoprotective effect after PH. S1888 Small Intestinal Bacterial Overgrowth as a Predictive Factor for Development of Diarrhea in HCC Patients Treated With Sorafenib Marialuisa Novi, Ernesto Cristiano Lauritano, Emanuele Rinninella, Annalisa Tortora, Michele Cosimo Santoro, Andrea Lupascu, Federico Barbaro, Maria Assunta Zocco, Immacolata A. Cazzato, Anna C. Piscaglia, Giovanni Gasbarrini, Antonio Gasbarrini Sorafenib is a multikinase inhibitor actually approved for the treatment of hepatocellular carcinoma (HCC).It is associated with several undesirable effects, particularly involving the gastrointestinal (GI) tract.Diarrhea is one ot the most common side effects, its severity ranging from mild to severe. Prophylaxis and management of this complication is crucial in the clinical practice to ensure an adequate drug regimen compliance.Recent data suggest that derangement of gut flora, in particular small intestinal bacterial overgrowth (SIBO) is highly prevalent in cirrhotic patients, due to decrease in small intestinal motility, multidrug therapy and failure of immune defense mechanisms.A potential synergic effect of SIBO with sorafenib on the onset of diarrhea could be reasonable and it was investigated in the study.AIMS & METHODS:15 Child-Pugh Class A cirrhotic patients affected by advanced HCC and with indication to sorafenib administration were enrolled. All patients were treated with sorafenib 400 mg bid.Bowel habit for one week preceding the start of therapy and every week for 5 following months was reported using Gastrointestinal Symptoms Rating Score.Before treatment, all patients were undergone 50 grams glucose breath test to investigate the presence of SIBO. Patients affected by SIBO were treated by rifaximin (1200 mg/die) at the onset of diarrhea and they repeated GBT to test SIBO decontamination one week after antibiotic treatment. RESULTS:SIBO was diagnosed in 60% of patients before starting treatment and it was characterized by a clinical paucisymptomatic presentation (GSRS<2). During the follow-up period, diarrhea developed in 78% of SIBO patients compared to 50% of SIBO negative group. The onset of diarrhea was within 7±2 days of the start of sorafenib in SIBO patients compared to 10±2 in SIBO negative patients. The mean GSRS score was higher in SIBO patients compared to SIBO negative group (4.7±0.3 vs 4.0±0.2). After antibiotic treatment, SIBO decontamination was obtained in 71% of patients and it was associated with a reduction of GSRS compared to not decontaminated patients(4.0±0.2 vs 4.5±0.3).Our preliminary results seem to suggest that small intestinal bacterial overgrowth could have a synergic effect with sorafenib on the onset of diarrhea and it is responsible for earlier and more severe discomfort. SIBO decontamination could be useful to reduce the severity of diarrhea. The present data should be confirmed by future large cohort trials evaluating different potential pathogenetic mechanisms of diarrhea.
S1886 Hepatitis C Virus is a Major Risk Factor for Hepatocellular Carcinoma in Somalis Abdirashid M. Shire, Dalbir S. Sandhu, Joseph Kaiya, Abdul M. Oseini, Gloria M. Petersen, Keith Knutson, Lewis R. Roberts Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are known risk factors for development of hepatocellular carcinoma (HCC). In the United States (US), the prevalence of HBV and HCV are relatively low. However, immigrant populations from Asia and subSaharan Africa may have substantially higher prevalence rates than the US general population and are consequently at significantly higher risk for development of HCC. The number of individuals of Somali ethnic background (Somalis) in Minnesota is believed to be around 50,000. AIM: To determine the prevalence of HBV and HCV infection among Somalis in Minnesota and the relative contributions of the two etiologies to HCC in Somalis. METHODS: The prevalence of HBV (using HBsAg and HBcAb) and HCV (using anti-HCV) infections and HCV genotypes was determined in Somali patients tested at Mayo Clinic Rochester from July 1996 to June 2009. Non-Somali patients tested for HBV and HCV during the same period served as controls. We also examined the role of HBV and HCV in the etiology of HCC among Somalis. RESULTS: The prevalence rates of HBsAg, HBcAb and anti-HCV positivity in Somalis were 13.4% (151/1125), 50.1% (391/780) and 9.97% (86/862) respectively; compared to the 1.09% (1292/118846), 7.68% (6453/ 84054) and 4.42% (4541/ 107186) in non-Somali patients. We found no significant difference in HBsAg and HBcAb positivity between male and female Somalis, but in non-Somali patients these were higher in males than in females [p<0.01 and p<0.01, respectively]. The HCV prevalence in male Somalis (12.9%, 54/417) was significantly higher than in female Somalis (7.19%, 32/445). HCV genotypes 1 (57.3%, 1666/2908) and 2 (11.0%, 321/2908) predominated in nonSomalis, while genotypes 3 (24.4%, 10/41) and 4 (41.5%, 17/41) were more common in Somalis. Of 30 Somali patients diagnosed with HCC, 5 (16.67%) were HBsAg positive, 19 (63.33%) were HBcAb positive, 23 (76.67%) were anti-HCV positive. Thirteen of the 30 HCC patients (43.33%) were positive for both HBcAb and anti-HCV. CONCLUSION: We found higher prevalence rates of both HBV and HCV in Somalis when compared with nonSomali patients; Somali males particularly showed a higher HCV prevalence. Additionally, the majority of Somalis who developed HCC (76.67%) were anti-HCV positive and 43.33% had evidence for prior HBV exposure as well as HCV infection (as shown by simultaneous HBcAb and anti-HCV positivity). Therefore, HCV and HBV infection are the two main etiologies contributing to HCC in Somalis. The results of this study will inform the development of strategies for prevention and early detection of HCC in Somalis. (Supported by KL2 grant 1KL2RR024151 to AS).
S1889 Trans-Peritoneal FNA Biopsy of Hilar Cholangiocarcinoma is Associated With Disease Metastasis Julie K. Heimbach, William Sanchez, Charles B. Rosen, Gregory J. Gores Background: hilar cholangiocarcinoma (CCA) presents both diagnostic and therapeutic challenges. Because of the pauci-cellular nature of the tumor, endoscopic biopsies and brushings may be negative, leading some physicians to pursue transperitoneal fine-needle aspiration (FNA) biopsies via a percutaneous or endoscopic ultrasound approach. While establishing a diagnosis is essential particularly for patients considering very aggressive treatment, a transperitoneal FNA may lead to seeding of the tumor. Thus, our Specific Aim was to determine whether patients who have undergone a percutaneous or trans-gastric FNA biopsy of the primary tumor have a higher incidence of metastatic CCA. Methods: outcomes of 181 patients enrolled in a combined neoadjuvant chemoradiotherapy followed by liver transplantation (LT) from 10/1/1992 to 11/1/2009 were analyzed. The incidence of metastatic disease found on pre-LT evaluation, including imaging and operative staging, as well as the incidence of disease recurrence following LT was compared between those who underwent a trans-peritoneal FNA biopsy of the primary tumor verus those who did not undergo a biopsy. Results: there were 5 patients with a percutaneous FNA biopsy of the primary tumor which was positive for adenocarcinoma and 4/5 (80%) were found to have disease spread directly into the peritoneum at operative staging, while the remaining patient had a negative staging operation but died in the perioperative period of technical complications. There were an additional 9 patients with hilar CCA who underwent percutaneous FNA biopsies which did not demonstrate tumor. All 9 staged negative and underwent subsequent LT, with one death from recurrent CCA and one death from PTLD in this group. Of those who did not undergo percutaneous FNA biopsy, the incidence of positive staging is 20% (31/ 149), p=0.0097 versus positive staging in those with a diagnostic percutaneous FNA by Fischer's exact test. Of these 31 who staged positive, 15 had lymph node metastasis, while the remaining 17 had direct extension or peritoneal metastasis (55%). Conclusions: transperitoneal FNA biopsy of hilar cholangiocarcinoma is associated with a higher rate of peritoneal metastases, and it should not be performed if a potentially curative approach such as LT is available.
S1887 Knockout of Sulfatase 2 (SULF2) Decreases Liver Regeneration After Partial Hepatectomy Ikuo Nakamura, Kadra H. Ahmed, Catherine D. Moser, Eric A. Hanse, Jeffrey H. Albrecht, Lewis R. Roberts Background and Aims: Liver regeneration plays an important role in liver transplantation and liver cancer treatment. Previously we showed that sulfatase 2 (SULF2) plays a critical role in tumorigenesis of hepatocellular carcinoma by activating heparin-binding growth factors In Vivo. Several heparin-binding growth factors are also important in liver regeneration. Little is known about how SULF2 affects normal hepatocytes during liver regeneration. The aim of this study was to determine the effects of SULF2 on liver regeneration after partial hepatectomy in mice. Methods: The model of liver regeneration after 70% partial hepatectomy (PH) was used in wild-type (WT) or SULF2 knockout (SULF2 KO) mice (6-8 weeks-old). We measured liver/body weight ratio, cell proliferation by BrdU immunohistochemistry, and counting mitotic figures and the expression of Cyclin D1 during liver regeneration. Liver injury was assessed by measuring serum ALT and apoptosis by TUNEL immunohistochemistry. Phosphorylation of the epidermal growth factor receptor (EGFR) was determined by Western immunoblotting. The circulating level of the cytokine IL-6 was determined by ELISA. Results: Knockout of SULF2 decreased the liver/body weight ratio at 7 days and BrdU positive nuclei at 36 and 48 and 72 hours after PH. The mitotic index in SULF2 KO
AASLD Abstracts
S-810
evaluated the outcome of combined transarterial chemoembolization (TACE) and percutaneous local ablation therapy in patients with advanced HCC. (Patient and methods) This study was conducted in 212 patients between January 1995 and December 2008 at Yokohama City University Hospital, Japan. We evaluated the combined therapy with TACE-alone or RFA- / PEI-alone in terms of the survival and recurrence rates, in each of 3 subgroups, as follows I: exceeding the Milan criteria, combined therapy (n=35) vs. TACE-alone (n=30), II: 2.5-5.0cm, single lesion, combined therapy (n=47) vs. RFA- / PEI-alone (n=16), III: within 3.0cm, 2-3 lesions, combined therapy (n=64) vs. RFA- / PEI-alone (n=20). (Results) In subgroup I, both the overall survival rate (OS) and the median survival time (MST) were significantly superior in the combined therapy group than in the TACE-alone group (OS: 1-, 3-, 5- and 7-year = 100% 52%, 33% and 25% vs. 84%, 26%, 0% and 0%, respectively, p=0.007, MST: 36 months vs. 21 months, p=0.013). In subgroup II, both the OS and local recurrence rate tended to be superior in the combined therapy group as compared with the values in the RFA- / PEI-alone group (OS: 1-, 3-, 5-, and 7-year = 98%, 67%, 55% and 38% vs. 93%, 58%, 38% and 13%, respectively, p=0.065, local recurrence rate: 1-, 3-, and 5-year = 4%, 19% and 19% vs. 7%, 33% and 33%, respectively, p=0.178). In subgroup III, both the OS and distant intra-hepatic recurrence rate tended to be superior in the combined therapy group than in the RFA- / PEI-alone group (OS: 1-, 3-, 5-, and 7-year = 97%, 72%, 54% and 27% vs. 100%, 80%, 27% and 0% respectively, p=0.105, distant intrahepatic recurrence rate: 1-, 3-, and 5-year = 4%, 51% and 70% vs. 13%, 65% and 82%, respectively, p=0.108). The influence of deterioration of hepatic function in the combined therapy group, TACE-alone group, and the RFA- / PEI-alone group were similar. (Conclusion) Combined TACE and RFA / PEI therapy was more effective than TACE alone in cases exceeding the Milan criteria, and more effective than RFA / PEI alone in cases with a single, large HCC or multiple HCCs fulfilling the Milan criteria. This study suggested that combined therapy may be the most effective strategy for advanced HCC.
mice decreased compared with WT mice at 48 hours after PH. Knockout of SULF2 decreased the expression of CyclinD1 at 36 and 48 hours. On the other hand, the levels of serum ALT in SULF2 KO mice were higher than in WT mice at 3 and 6 hours and the number of TUNEL positive cells in SULF2 KO mice was higher at day 3 after PH. The phosphorylation of EGFR in SULF2 KO mice decreased at 3 and 6 hours after PH. The level of serum IL-6 in mice lacking SULF2 increased at 3 hours after PH. Conclusions: The absence of SULF2 impairs liver regeneration and increased liver damage and apoptosis after PH. Our results suggest that SULF2 plays a role in liver regeneration by modulating EGFR signaling and has a hepatoprotective effect after PH. S1888 Small Intestinal Bacterial Overgrowth as a Predictive Factor for Development of Diarrhea in HCC Patients Treated With Sorafenib Marialuisa Novi, Ernesto Cristiano Lauritano, Emanuele Rinninella, Annalisa Tortora, Michele Cosimo Santoro, Andrea Lupascu, Federico Barbaro, Maria Assunta Zocco, Immacolata A. Cazzato, Anna C. Piscaglia, Giovanni Gasbarrini, Antonio Gasbarrini Sorafenib is a multikinase inhibitor actually approved for the treatment of hepatocellular carcinoma (HCC).It is associated with several undesirable effects, particularly involving the gastrointestinal (GI) tract.Diarrhea is one ot the most common side effects, its severity ranging from mild to severe. Prophylaxis and management of this complication is crucial in the clinical practice to ensure an adequate drug regimen compliance.Recent data suggest that derangement of gut flora, in particular small intestinal bacterial overgrowth (SIBO) is highly prevalent in cirrhotic patients, due to decrease in small intestinal motility, multidrug therapy and failure of immune defense mechanisms.A potential synergic effect of SIBO with sorafenib on the onset of diarrhea could be reasonable and it was investigated in the study.AIMS & METHODS:15 Child-Pugh Class A cirrhotic patients affected by advanced HCC and with indication to sorafenib administration were enrolled. All patients were treated with sorafenib 400 mg bid.Bowel habit for one week preceding the start of therapy and every week for 5 following months was reported using Gastrointestinal Symptoms Rating Score.Before treatment, all patients were undergone 50 grams glucose breath test to investigate the presence of SIBO. Patients affected by SIBO were treated by rifaximin (1200 mg/die) at the onset of diarrhea and they repeated GBT to test SIBO decontamination one week after antibiotic treatment. RESULTS:SIBO was diagnosed in 60% of patients before starting treatment and it was characterized by a clinical paucisymptomatic presentation (GSRS<2). During the follow-up period, diarrhea developed in 78% of SIBO patients compared to 50% of SIBO negative group. The onset of diarrhea was within 7±2 days of the start of sorafenib in SIBO patients compared to 10±2 in SIBO negative patients. The mean GSRS score was higher in SIBO patients compared to SIBO negative group (4.7±0.3 vs 4.0±0.2). After antibiotic treatment, SIBO decontamination was obtained in 71% of patients and it was associated with a reduction of GSRS compared to not decontaminated patients(4.0±0.2 vs 4.5±0.3).Our preliminary results seem to suggest that small intestinal bacterial overgrowth could have a synergic effect with sorafenib on the onset of diarrhea and it is responsible for earlier and more severe discomfort. SIBO decontamination could be useful to reduce the severity of diarrhea. The present data should be confirmed by future large cohort trials evaluating different potential pathogenetic mechanisms of diarrhea.
S1886 Hepatitis C Virus is a Major Risk Factor for Hepatocellular Carcinoma in Somalis Abdirashid M. Shire, Dalbir S. Sandhu, Joseph Kaiya, Abdul M. Oseini, Gloria M. Petersen, Keith Knutson, Lewis R. Roberts Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are known risk factors for development of hepatocellular carcinoma (HCC). In the United States (US), the prevalence of HBV and HCV are relatively low. However, immigrant populations from Asia and subSaharan Africa may have substantially higher prevalence rates than the US general population and are consequently at significantly higher risk for development of HCC. The number of individuals of Somali ethnic background (Somalis) in Minnesota is believed to be around 50,000. AIM: To determine the prevalence of HBV and HCV infection among Somalis in Minnesota and the relative contributions of the two etiologies to HCC in Somalis. METHODS: The prevalence of HBV (using HBsAg and HBcAb) and HCV (using anti-HCV) infections and HCV genotypes was determined in Somali patients tested at Mayo Clinic Rochester from July 1996 to June 2009. Non-Somali patients tested for HBV and HCV during the same period served as controls. We also examined the role of HBV and HCV in the etiology of HCC among Somalis. RESULTS: The prevalence rates of HBsAg, HBcAb and anti-HCV positivity in Somalis were 13.4% (151/1125), 50.1% (391/780) and 9.97% (86/862) respectively; compared to the 1.09% (1292/118846), 7.68% (6453/ 84054) and 4.42% (4541/ 107186) in non-Somali patients. We found no significant difference in HBsAg and HBcAb positivity between male and female Somalis, but in non-Somali patients these were higher in males than in females [p<0.01 and p<0.01, respectively]. The HCV prevalence in male Somalis (12.9%, 54/417) was significantly higher than in female Somalis (7.19%, 32/445). HCV genotypes 1 (57.3%, 1666/2908) and 2 (11.0%, 321/2908) predominated in nonSomalis, while genotypes 3 (24.4%, 10/41) and 4 (41.5%, 17/41) were more common in Somalis. Of 30 Somali patients diagnosed with HCC, 5 (16.67%) were HBsAg positive, 19 (63.33%) were HBcAb positive, 23 (76.67%) were anti-HCV positive. Thirteen of the 30 HCC patients (43.33%) were positive for both HBcAb and anti-HCV. CONCLUSION: We found higher prevalence rates of both HBV and HCV in Somalis when compared with nonSomali patients; Somali males particularly showed a higher HCV prevalence. Additionally, the majority of Somalis who developed HCC (76.67%) were anti-HCV positive and 43.33% had evidence for prior HBV exposure as well as HCV infection (as shown by simultaneous HBcAb and anti-HCV positivity). Therefore, HCV and HBV infection are the two main etiologies contributing to HCC in Somalis. The results of this study will inform the development of strategies for prevention and early detection of HCC in Somalis. (Supported by KL2 grant 1KL2RR024151 to AS).
S1889 Trans-Peritoneal FNA Biopsy of Hilar Cholangiocarcinoma is Associated With Disease Metastasis Julie K. Heimbach, William Sanchez, Charles B. Rosen, Gregory J. Gores Background: hilar cholangiocarcinoma (CCA) presents both diagnostic and therapeutic challenges. Because of the pauci-cellular nature of the tumor, endoscopic biopsies and brushings may be negative, leading some physicians to pursue transperitoneal fine-needle aspiration (FNA) biopsies via a percutaneous or endoscopic ultrasound approach. While establishing a diagnosis is essential particularly for patients considering very aggressive treatment, a transperitoneal FNA may lead to seeding of the tumor. Thus, our Specific Aim was to determine whether patients who have undergone a percutaneous or trans-gastric FNA biopsy of the primary tumor have a higher incidence of metastatic CCA. Methods: outcomes of 181 patients enrolled in a combined neoadjuvant chemoradiotherapy followed by liver transplantation (LT) from 10/1/1992 to 11/1/2009 were analyzed. The incidence of metastatic disease found on pre-LT evaluation, including imaging and operative staging, as well as the incidence of disease recurrence following LT was compared between those who underwent a trans-peritoneal FNA biopsy of the primary tumor verus those who did not undergo a biopsy. Results: there were 5 patients with a percutaneous FNA biopsy of the primary tumor which was positive for adenocarcinoma and 4/5 (80%) were found to have disease spread directly into the peritoneum at operative staging, while the remaining patient had a negative staging operation but died in the perioperative period of technical complications. There were an additional 9 patients with hilar CCA who underwent percutaneous FNA biopsies which did not demonstrate tumor. All 9 staged negative and underwent subsequent LT, with one death from recurrent CCA and one death from PTLD in this group. Of those who did not undergo percutaneous FNA biopsy, the incidence of positive staging is 20% (31/ 149), p=0.0097 versus positive staging in those with a diagnostic percutaneous FNA by Fischer's exact test. Of these 31 who staged positive, 15 had lymph node metastasis, while the remaining 17 had direct extension or peritoneal metastasis (55%). Conclusions: transperitoneal FNA biopsy of hilar cholangiocarcinoma is associated with a higher rate of peritoneal metastases, and it should not be performed if a potentially curative approach such as LT is available.
S1887 Knockout of Sulfatase 2 (SULF2) Decreases Liver Regeneration After Partial Hepatectomy Ikuo Nakamura, Kadra H. Ahmed, Catherine D. Moser, Eric A. Hanse, Jeffrey H. Albrecht, Lewis R. Roberts Background and Aims: Liver regeneration plays an important role in liver transplantation and liver cancer treatment. Previously we showed that sulfatase 2 (SULF2) plays a critical role in tumorigenesis of hepatocellular carcinoma by activating heparin-binding growth factors In Vivo. Several heparin-binding growth factors are also important in liver regeneration. Little is known about how SULF2 affects normal hepatocytes during liver regeneration. The aim of this study was to determine the effects of SULF2 on liver regeneration after partial hepatectomy in mice. Methods: The model of liver regeneration after 70% partial hepatectomy (PH) was used in wild-type (WT) or SULF2 knockout (SULF2 KO) mice (6-8 weeks-old). We measured liver/body weight ratio, cell proliferation by BrdU immunohistochemistry, and counting mitotic figures and the expression of Cyclin D1 during liver regeneration. Liver injury was assessed by measuring serum ALT and apoptosis by TUNEL immunohistochemistry. Phosphorylation of the epidermal growth factor receptor (EGFR) was determined by Western immunoblotting. The circulating level of the cytokine IL-6 was determined by ELISA. Results: Knockout of SULF2 decreased the liver/body weight ratio at 7 days and BrdU positive nuclei at 36 and 48 and 72 hours after PH. The mitotic index in SULF2 KO
AASLD Abstracts
S-810