Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

Soe, Kyaw; Hishikawa, Yoshitaka; Fukuzawa, Yoshitaka; Win, Ne; Yin, Khine San; Win, Khin Maung; Myint, Aye Aye; Koji, Takehiko

doi:10.1007/s00535-006-1993-9

Cited by 9 publications

(8 citation statements)

References 49 publications

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“…In contrast to patients without inherent hemoglobinopathy, ribavirin, that is one of the major determinants of the SVR, can induce life-threatening anemia in thalassemia major patients, and thus, is generally considered contraindicated in these patients [11][12]. In addition to contraindication of ribavirin, high iron content of serum and liver with its probable role in conferring patients’ interferon resistance and its synergistic effect on progression of liver fibrosis is another major confounder in treatment of thalassemia major patients [13][14][15][16][17][18][19]. Previously in a meta-analysis of literature, we showed that peginterferon monotherapy can induce a SVR rate of 28 percent in thalassemia major patients, while combination therapy of peginterferon and ribavirin (low dose therapy, accompanying by tight monitoring of patients) elicits a SVR rate of 44 percent [20].…”

Section: Introductionmentioning

confidence: 99%

Low Dose Ribavirin for Treatment of Hepatitis C Virus Infected Thalassemia Major Patients; New Indications for Combination Therapy

et al. 2012

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Background Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. Objectives Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far. Patients and Methods Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (≥ 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study. Results Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin. Conclusions According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.

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Section: Introductionmentioning

confidence: 99%

Low Dose Ribavirin for Treatment of Hepatitis C Virus Infected Thalassemia Major Patients; New Indications for Combination Therapy

et al. 2012

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“…Moreover, apoptosis is involved in several human diseases, including autoimmune diseases, viral hepatitis, hepatocellular carcinoma, ischemia-reperfusion injury (I/R injury), and gastro-intestinal malignancies (1)(2)(3)(4)(5). In the case of liver transplantation, apoptosis in liver allografts was first reported in a porcine model in 1974 (6).…”

Section: Introductionmentioning

confidence: 99%

Diverse Effects of FK506 on the Apoptosis of Hepatocytes and Infiltrating Lymphocytes in an Allografted Rat Liver

Moriuchi

Kamohara

Eguchi

et al. 2011

Journal of Surgical Research

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“…Furthermore, long-term treatment of patients with chronic HCV infection with iron-reducing agents results in a significant improvement of liver function and marked reduction in the progression to HCC [32,33]. In another study [34], iron deposition was found in 43% of the HCC cases and indicated that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis, by promoting cancer cell proliferation, without affecting the Fas/FasL apoptotic system. A recently study [35] showed that chronic iron overload seemed to induce nuclear localization of MT and NF-jB activation, with a resultant marked acceleration of liver regeneration in ironoverload rats after PH occurring at least 12 h earlier than that in normal-diet rats.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, there is not yet any evidence to support the correlation of iron deposit in HCC patients with the concentration of iron in groundwater would be indicated in the previous studies. In an excellent work from Soe et al [34] in Japan, Prussian blue staining was performed in order to detect iron deposition, and the iron deposition was found in 43% of the HCC cases. The study showed that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Geographic patterns of hepatocellular carcinoma mortality with exposure to iron in groundwater in Taiwanese population: An ecological study

Shyu

Lung

et al. 2013

BMC Public Health

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BackgroundMany studies have examined the risk factors for HCC (including hepatitis B virus, hepatitis C virus, aflatoxin, retinol, cigarette smoking, and alcohol consumption). However, data from previous studies on the association between iron exposure, land subsidence, and HCC mortality/incidence were limited, especially in Taiwanese population. We aimed to explore the geographical distribution of HCC mortality rates by township-specific data and to evaluate the association between HCC mortality, land subsidence, and iron levels in groundwater in Taiwan.MethodsWe conducted an ecological study and calculated the HCC age-standardized mortality/incidence rates according to death certificates issued in Taiwan from 1992 to 2001 and incidence data from 1995–1998. The land subsidence dataset before 2005 and iron concentrations in groundwater in 1989 are also involved in this study. Both geographical information systems and Pearson correlation coefficients were used to analyze the relationship between HCC mortality rates, land subsidence, and iron concentrations in groundwater.ResultsTownship-specific HCC mortality rates are higher in southwestern coastal townships where serious land subsidence and higher township-specific concentrations of iron in groundwater are present. The Pearson correlation coefficients of iron concentrations in groundwater and ASRs of HCC were 0.286 (P = 0.004) in males and 0.192 (P = 0.058) in females for mortality data; the coefficients were 0.375 (P < 0.001) in males and 0.210 (P = 0.038) in females for incidence data.ConclusionsThis study showed that HCC mortality is clustered in southwestern Taiwan and the association with the iron levels in groundwater in Taiwanese population warrant further investigation.

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Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

Abstract: Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma)

Cited by 9 publications

References 49 publications

Low Dose Ribavirin for Treatment of Hepatitis C Virus Infected Thalassemia Major Patients; New Indications for Combination Therapy

Low Dose Ribavirin for Treatment of Hepatitis C Virus Infected Thalassemia Major Patients; New Indications for Combination Therapy

Diverse Effects of FK506 on the Apoptosis of Hepatocytes and Infiltrating Lymphocytes in an Allografted Rat Liver

Geographic patterns of hepatocellular carcinoma mortality with exposure to iron in groundwater in Taiwanese population: An ecological study

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