- Transplant Hepatology
- liver cancer
- Liver Mass
Clinical Associate Professor, Medicine - Gastroenterology & Hepatology
Residency: Griffin Hospital (2006) CT
Board Certification: American Board of Internal Medicine, Transplant Hepatology (2014)
Fellowship: Beth Israel Deaconess Medical Center Dept of Gastroenterology (2012) MA
Fellowship: Beth Israel Deaconess Medical Center Dept of Gastroenterology (2011) MA
Residency: Cambridge Health Alliance Internal Medicine Residency (2008) MA
Medical Education: Shahid Beheshti University of Medical Sciences (1998) Iran
Graduate and Fellowship Programs
Gastroenterology & Hepatology (Fellowship Program)
Downstaging Hepatocellular Carcinoma before Liver Transplantation: A Multicenter Analysis of the "All-Comers" Protocol in the MERITS-LT Consortium.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Patients with HCC meeting UNOS-downstaging (DS) criteria have excellent liver transplant (LT) outcomes after downstaging. However, outcomes for "all-comers" (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n=82) or UNOS-DS (n=229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months;p<0.001). 3-year-survival was 69% for UNOS-DS vs. 58% for AC (p=0.05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or AFP >500. Five-year LT probability was 42% for AC vs. 74% in UNOS-DS (p=0.10). Thirty-eight percent were under-staged on explant with increasing sum of largest tumor diameter plus number of lesions prior to LT (OR 1.3;p=0.01) and AFP>20 (OR 5.9;p=0.005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (p=0.67). In this first prospective multi-regional study of AC patients from the MERITS-LT Consortium, we observed a 65% probability of successful downstaging. Three-year survival in AC was nearly 60% though AC with Child-Pugh B/C or AFP >500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts suggesting that LT is a reasonable goal in selected AC patients.
View details for DOI 10.1016/j.ajt.2023.07.021
View details for PubMedID 37532179
- Accuracy of Information Provided by ChatGPT Regarding Liver Cancer Surveillance and Diagnosis. AJR. American journal of roentgenology 2023
Recall patterns and risk of primary liver cancer for subcentimeter ultrasound liver observations: a multicenter study.
2023; 7 (3)
BACKGROUND: Patients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC).AIMS: The aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound.METHODS: We conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively.RESULTS: Of 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7cm (interquartile range: 0.5-0.8cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08).CONCLUSIONS: Recall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.
View details for DOI 10.1097/HC9.0000000000000073
View details for PubMedID 36881615
VARIATION IN SURVEILLANCE PATTERNS AND RISK OF PRIMARY LIVER CANCER FOR SUB-CENTIMETER LIVER LESIONS ON ABDOMINAL ULTRASOUND
WILEY. 2022: S1388-S1389
View details for Web of Science ID 000870796604245
Clinical characteristics and outcomes in those with primary extrahepatic malignancy and malignant ascites.
2022; 22 (1): 410
BACKGROUND: Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.METHODS: 241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.RESULTS: Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.CONCLUSIONS: Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
View details for DOI 10.1186/s12876-022-02487-4
View details for PubMedID 36064324
Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy.
Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). The aim of this study was to explore the incidence of HCC in a cohort of subjects with HBV and correlate with HBV treatment current guidance. We identified 2846 subjects with HBV over the study period. HCC was diagnosed in 386 of 2846 (14%) subjects; 209 of 386 (54%) were on nucleos(t)ide analogue (NA) therapy at time of HCC diagnosis, and 177 of 386 (46%) were not on NA therapy. Of the 177 subjects not on NAs who developed HCC during follow-up, 153 of 177 (86%) had cirrhosis. Within the 177 subjects not on NAs, 158 of 177 (89%) had undetectable HBV DNA, 10 of 177 (6%) had detectable HBV DNA < 2000 IU/L, and 9 of 177 (5%) had HBV DNA > 2000 IU/L. Of those with cirrhosis and undetectable HBV DNA, 115 of 141 had compensated cirrhosis, and 26 of 141 had decompensated cirrhosis. Significant predictors of HCC on time to event analysis included cirrhosis (hazard ratio [HR] 10, 95% confidence interval [CI] 5.8-17.5; p < 0.001), alanine aminotransferase level (HR 1.004, 95% CI 1.002-1.006; p < 0.001), age (HR 1.04, 95% CI 1.03-1.06; p < 0.001), (HR 1.9, 95% CI 1.2-3.1; p 0.007), and nonalcoholic fatty liver disease (HR 1.7, 95% CI 1.1-2.8; p 0.02). Kaplan-Meier analysis demonstrated the cumulative incidence of HCC in subjects with compensated cirrhosis receiving NA therapy was significantly lower compared to subjects with compensated cirrhosis outside current HBV treatment practice guidance (undetectable HBV DNA) (32% vs. 51%; p < 0.001). Conclusion: Those with untreated compensated cirrhosis with undetectable HBV DNA who do not meet current guidance for treatment had higher rates of HCC than those with compensated cirrhosis and suppressed HBV DNA by NA therapy. This study highlights the need for earlier diagnosis and treatment of HBV.
View details for DOI 10.1002/hep4.2064
View details for PubMedID 36004713
Decreased urgency among liver transplant candidates with hepatocellular carcinoma in the United States.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Early-stage hepatocellular carcinoma (HCC) has been an accepted indication for liver transplantation now for over 20 years. Allocation policy in the United States (US) has been continually refined to maintain equity and optimize the utility of transplant for HCC, yet all patients qualifying for HCC exception still receive the same number of points. This group is quite heterogeneous, with varying risk of waitlist dropout dependent on tumor characteristics including number and size of lesions and alpha-fetoprotein (AFP) level, as well as baseline liver function. In addition, changing demographics of liver disease, including the rising incidence of NASH, effective antiviral therapy for hepatitis C virus, and earlier detection of HCC due to improved screening programs and awareness, may influence the overall survival benefit to liver transplantation.
View details for DOI 10.1002/lt.26373
View details for PubMedID 34806834
National Trends and Waitlist Outcomes of Locoregional Therapy among Liver Transplant Candidates with Hepatocellular Carcinoma in the United States.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS: Policy changes in the United States (US) have overall lengthened waiting times for patients with hepatocellular carcinoma (HCC). We investigate temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the US.METHODS: Data for primary adult LT candidates listed from 2003-2018 who received HCC exception were extracted from the OPTN database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout.RESULTS: There were 31,609 eligible patients with at least one approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least one LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. Increased incidence of LRT was observed among patients with tumor burden beyond Milan, higher AFP, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there were no significant differences by number of LRT. In IPTW-adjusted analysis, radioembolization or ablation as the first LRT was associated with reduced risk of waitlist dropout compared to chemoembolization.CONCLUSIONS: In a large nationwide cohort of LT candidates with HCC, LRT and in particular radioembolization was increasingly used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout.
View details for DOI 10.1016/j.cgh.2021.07.048
View details for PubMedID 34358718
- How Clinicians May Use Tests of Hepatic Function Now and In the Future. Translational research : the journal of laboratory and clinical medicine 2021
Down-staging Outcomes for Hepatocellular Carcinoma: Results from the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium.
United Network of Organ Sharing (UNOS) has adopted uniform criteria for down-staging (UNOS-DS) of hepatocellular carcinoma (HCC) prior to liver transplantation (LT), but down-staging success rate and intention-to-treat outcomes across broad geographic regions are unknown.In this first multi-regional study (7 centers, 4 UNOS regions), consecutive patients with HCC undergoing down-staging based on UNOS-DS criteria were prospectively evaluated from 2016-2019 (n=209).Probability of successful down-staging to Milan criteria and dropout at 2 years from initial down-staging procedure was 87.7% and 37.3%, respectively. Pre-treatment AFP-L3 >10% (HR 3.7, p=0.02) was associated with increased dropout risk. When comparing chemoembolization (n=132) and Y-90 radioembolization (n=62) as initial down-staging treatment, there were no differences in mRECIST response, probability of or time to successful down-staging, waitlist dropout or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion and 42.8% exceeded Milan criteria (under-staging). The only factor associated with under-staging was the sum of the number of lesions plus largest tumor diameter on last pre-LT imaging, and odds of under-staging increased by 35% per 1 unit increase in this sum. Post-LT survival at 2 years was 95% and HCC recurrence occurred in 7.9%.In this first prospective multi-regional study based on UNOS-DS criteria, we observed successful down-staging rate of >80%, and similar efficacy of chemoembolization and Y-90 radioembolization as initial down-staging treatment. A high rate of tumor under-staging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor under-staging.
View details for DOI 10.1053/j.gastro.2021.07.033
View details for PubMedID 34331914
Recent Progress in Systemic Therapy for Hepatocellular Cancer (HCC).
Current Treatment Options in Gastroenterology
2021; 19 (1): 351–368
View details for DOI 10.1007/s11938-021-00346-x
THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B VIRUS INFECTION SUBJECTS NOT MEETING CRITERIA FOR ANTIVIRAL THERAPY
WILEY. 2020: 472A–473A
View details for Web of Science ID 000574027001230
Characterizing Ascites in Subjects With Nonhepatic Solid Tumors
LIPPINCOTT WILLIAMS & WILKINS. 2020: S507
View details for Web of Science ID 000607196702295
Post-Transplant Outcomes in Older Patients with Hepatocellular Carcinoma (HCC) are Driven by non-HCC Factors.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
The incidence of hepatocellular carcinoma (HCC) is growing in the US, especially among the elderly. Older patients are increasingly getting transplanted for HCC, but the impact of advancing age on long-term post-transplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium (UMHTC) of 4980 patients. We divided the patients into 4 groups by age at transplantation- 18-64 (n = 4001), 65-69 (n = 683), 70-74 (n = 252) and ≥ 75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age over 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (p = 0.004), and not HCC-related death (p = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients transplanted for HCC (n = 302). Patients older than 65 years had a higher incidence of de-novo cancer (18.1% vs 7.6%, p = 0.006) after transplantation and higher overall cancer-related mortality (14.3% vs 6.6%, p = 0.03). CONCLUSION: Even carefully selected elderly patients with HCC have significantly worse post-transplant survival, which are mostly driven by non-HCC related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve outcomes in elderly patients transplanted for HCC.
View details for DOI 10.1002/lt.25974
View details for PubMedID 33306254
Acute Fatty Liver Disease of Pregnancy: Updates in Pathogenesis, Diagnosis, and Management
AMERICAN JOURNAL OF GASTROENTEROLOGY
2017; 112 (6): 838-846
Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver failure and may have complications for the mother and fetus, including death. This review examines recent literature on the epidemiology, pathogenesis, diagnosis, and treatment of acute fatty liver of pregnancy. Pathogenesis of this disease has been linked to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty acid oxidation. The value of screening all patients for these genetic defects remains to be determined. Distinguishing AFLP from other high-risk liver diseases of pregnancy that have overlap features, such as HELLP and preeclampsia, can be challenging. Although sensitive diagnostic tools such as the Swansea criteria have been developed, further work is needed to diagnose AFLP more quickly. Although survival rates have improved in the past 30 years, delay in diagnosis and treatment of AFLP has life-threatening consequences; an algorithmic approach to AFLP may be a valuable resource for clinicians. Future epidemiological and long-term studies will improve our prediction of women at risk for developing AFLP and determine the long-term consequences of this condition.
View details for DOI 10.1038/ajg.2017.54
View details for Web of Science ID 000402710000010
View details for PubMedID 28291236
Aspirin use is associated with lower indices of liver fibrosis among adults in the United States
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
2016; 43 (6): 734-743
Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti-platelet agents decrease liver fibrosis. It is unknown whether platelet inhibition by aspirin prevents liver fibrosis in humans.To examine the association between aspirin use and liver fibrosis among adults with suspected chronic liver disease.We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey III. We identified 1856 individuals with suspected chronic liver disease (CLD). The degree of liver fibrosis was determined using four validated fibrosis indices and a composite index.The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS [0.24 standard deviation (s.d.) units lower; 95% CI -0.42 to -0.06, P = 0.009]. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected CLD compared to those without (-0.23 vs. -0.03 s.d. units; P interaction = 0.05). The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices (P = 0.002-0.08) in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses.The use of aspirin was associated with significantly lower indices of liver fibrosis among US adults with suspected chronic liver diseases. Aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.
View details for DOI 10.1111/apt.13515
View details for Web of Science ID 000370644700007
View details for PubMedID 26749582
Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome
WORLD JOURNAL OF GASTROENTEROLOGY
2014; 20 (39): 14142-14155
Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.
View details for DOI 10.3748/wjg.v20.i39.14142
View details for Web of Science ID 000343881500007
View details for PubMedID 25339803
View details for PubMedCentralID PMC4202345
Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection
2007; 37 (3): 172-178
We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection.Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls.Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade.Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.
View details for DOI 10.1111/j.1872-034X.2007.00026.x
View details for Web of Science ID 000244776500003
View details for PubMedID 17362299
HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells
JOURNAL OF HEPATOLOGY
2006; 45 (1): 5-12
Hepatitis C infection induces hepatic oxidative stress. Heme oxygenase (HO), the rate-controlling enzyme of heme catabolism, plays a key role as a protector against oxidative, and other stresses. Other recent work has implicated Bach1, a heme binding protein that represses gene expression, in the regulation of HO-1 gene expression.We investigated the effects of HCV polyprotein expression on expression of HO-1 and Bach1 genes in human hepatoma cells (Huh-7 cells).HO-1 was up-regulated in the cell line expressing HCV proteins from core up to the aminoterminal domain of NS3. Addition of increasing concentrations of N-acetylcysteine (NAC) led to down-regulation of HO-1 in cells expressing HCV proteins. In contrast, Bach1 was significantly down-regulated in these cells. Sodium arsenite, a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type Huh-7 cells, and NAC partially abrogated this decrease.Huh-7 cells expressing HCV proteins show significant up-regulation of the HO-1 gene, and reciprocal down-regulation of the Bach1 gene. Exogenous oxidative stressors and anti-oxidants can modulate expression of these genes. These and other results suggest a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic effects of HCV proteins in human hepatocytes.
View details for DOI 10.1016/j.jhep.2005.12.020
View details for Web of Science ID 000238782200002
View details for PubMedID 16530877
Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells - Insights from studies with small interfering RNAs
JOURNAL OF BIOLOGICAL CHEMISTRY
2004; 279 (50): 51769-51774
Heme oxygenase-1 is an antioxidant defense enzyme that converts heme to biliverdin, iron, and carbon monoxide. Bach-1 is a bZip protein that forms heterodimers with small Maf proteins and was reported recently to down-regulate the HO-1 gene in mice. Using small interfering RNAs targeted to human Bach-1 mRNA, we investigated whether modulation of human hepatic Bach-1 expression by small interfering (si)RNA technology influences heme oxygenase-1 gene expression. We found that Bach-1 siRNAs transfected into Huh-7 cells significantly reduced Bach-1 mRNA and protein levels approximately 80%, compared with non siRNA-treated cells. In contrast, transfection with the same amounts of nonspecific control duplexes or LaminB2-duplex did not reduce Bach-1 mRNA or protein levels, confirming the specificity of Bach-1 siRNA. Expression of the heme oxygenase-1 gene in Bach-1 siRNA-transfected cells was up-regulated 7-fold, compared with cells without Bach-1 siRNA. The effect of increasing concentrations of heme to up-regulate levels of heme oxygenase-1 was more pronounced when Bach-1 siRNA was present. Taken together, these results indicated that Bach-1 has a specific and selective ability to repress expression of human hepatic heme oxygenase-1. Silencing of Bach-1 by siRNAs is a useful method for up-regulating HO-1 gene expression. Exogenous heme produces additional up-regulation, beyond that produced by Bach-1 siRNAs, suggesting that heme does not act solely through its effects on Bach-1.
View details for DOI 10.1074/jbc.M409463200
View details for Web of Science ID 000225493400009
View details for PubMedID 15465821