Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the role of retinoblastoma (Rb) gene alteration in hepatocarcinogenesis, we examined Rb protein expression immuno-histochemically in a series of surgically resected specimens including non-cancerous liver tissues with cirrhosis or chronic hepatitis, large regenerative nodules, pre-cancerous adenomatous hyperplasias as well as primary and metastatic lesions of hepatocellular carcinoma (HCC). All of the non-cancerous liver tissues, large regenerative nodules and adenomatous hyperplasias showed normal Rb protein expression. Altered Rb protein expression was observed in 31 (lack of Rb protein in 16 and over-expression in 15) of the 81 primary HCCs (38%) and was significantly associated with tumor differentiation grade: altered Rb protein expression occurred in 1 of 23 (4%), 16 of 43 (37%) and 14 of 15 (93%) well-, moderately and poorly differentiated tumors (moderately vs. well-differentiated p < 0.01; poorly vs. moderately differentiated p < 0.001). Incidences of both Rb protein absence and over-expression were higher for moderately differentiated than for well-differentiated tumors and even higher for poorly differentiated tumors. Rb protein absence and over-expression were observed in 9 (39%) and 10 (44%) of the 23 metastatic lesions of HCC, respectively, and the incidence of altered Rb protein expression (absence or over-expression) was significantly higher than in primary lesions (83% vs. 38%, p < 0.001). Our observations suggest that elevated and absent Rb protein are closely associated with tumor progression and developing metastatic disease rather than tumor initiation in cases of HCC. Int. J. Cancer (Pred. Oncol.) 84:604-608, 1999.
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PMID:Over-expression and lack of retinoblastoma protein are associated with tumor progression and metastasis in hepatocellular carcinoma. 1056 6

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 x 10(6), 3 times a week, for 1 year) (n = 30) or symptomatic treatment (n = 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 +/- 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of alpha-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P =. 19, log rank P =.14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression (P =.17), or deterioration of Child-Pugh class (P =.37), performance status (P =. 07), or Okuda stage (P =.44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival.
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PMID:Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. 1061 28

Generally, 0.4-2.5% of patients with chronic hepatitis C virus (HCV) infection develop hepatocellular carcinoma (HCC). HCC occurs more often in patients with cirrhosis and in those with increased liver cell proliferation. HCV-related tumors occur in older patients and often have a less aggressive course than HCC, related to other etiological factors. Many HCV-related HCC are multifocal in origin. However, many tumors grow as a single hepatic nodule for years before generating satellite or distant tumor nodules. The growth pattern varies from one tumor to another, with tumor volume doubling times ranging from 1 to 20 months. Tumor progression and hepatic failure are the leading causes of death in most patients. Using the polymerase chain reaction technique, HCV-RNA has been almost invariably detected in serum and tumor tissue of anti-HCV patients with HCC. In many patients, HCV-RNA was found to belong to the possibly more pathogenic type 1b. However, it is unlikely that HCV plays a direct role in liver tumorogenesis, since no reverse transcriptase activity has been found in infected livers. One current opinion is that HCV may promote cancer through cirrhosis, which is per se an important risk factor for this tumor. In HCV carriers, the risk of developing HCC and having more severe tumor disease may be increased by coexisting hepatitis B virus (HBV) or alcohol abuse, further supporting the idea that both HCC and cirrhosis might be a result of the interplay of several risk factors. HCC could also be the consequence of HCV interacting with cellular genes that regulate cell growth and differentiation, independent of the effect of cirrhosis.
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PMID:Natural history and pathogenesis of hepatitis C virus related hepatocellular carcinoma. 1062 56

The sequential development of cirrhosis and hepatocellular carcinoma (HCC) in patients with transfusion-associated hepatitis was a clue leading to the identification of hepatitis C virus (HCV) as a risk factor for HCC. The incidence of HCV-related liver cancer is increasing in many developed countries: tumours arise in older patients, are almost invariably associated with cirrhosis and often have a less aggressive course than is seen in HCC related to other aetiological factors. Most HCCs grow as a single hepatic nodule for several years before generating satellite or distant tumour nodules. Tumour progression and hepatic failure are the leading causes of death. HCV might promote cancer through cirrhosis, which is per se an important risk factor for this tumour. HCV might also have oncogenic properties by interacting with cellular genes that regulate cell growth and differentiation. The primary prevention of HCC through vaccination against HCV is not yet available. The treatment of patients with chronic hepatitis C with interferon might attenuate the risk of HCC.
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PMID:Hepatitis C virus and hepatocellular carcinoma. 1065 17

We prospectively analyzed p15 methylation patterns in 25 surgically resected tumors and 130 plasma, serum, and buffy coat samples from hepatocellular carcinoma (HCC) patients, controls with chronic hepatitis/cirrhosis, and healthy subjects. Using methylation-specific PCR, we demonstrated for the first time p15 promoter methylation in 64% of tumors and 25% (4 of 16) of patients' plasma and serum samples. Concurrent p15 and p16 methylation was shown in 48% of tumors, and p15/p16 methylation was detected in the plasma/serum of 92% (11 of 12) of patients. Of note, 75% of 12 patients with concurrent tumor methylation developed clinical metastasis/recurrence (P = 0.027). In buffy coat samples, p15 methylation was detected in all eight patients with tumor p15 methylation, suggesting the presence of circulating tumor cells. None of the control samples were methylation positive. Our data underscore the important role(s) of p15 and p16 methylation in hepatocarcinogenesis and tumor progression. Among 92% (23 of 25) of patients with tumor p15/p16 methylation, circulating tumor DNA and HCC cells were detected in the peripheral blood of 87% (20 of 23) of patients. The combination of these epigenetic markers may prove valuable for noninvasive HCC diagnosis and disease monitoring.
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PMID:Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. 1099 38

The worldwide incidence of hepatocellular carcinoma (HCC) is approximately one million cases a year. This makes HCC one of the most frequent human malignancies, especially in Asia and Africa, although the incidence is increasing also in the western world. HCC is a complication of chronic liver disease, with cirrhosis as the most important risk factor. Viral co-pathogenesis makes cirrhosis due to hepatitis B (HBV) and hepatitis C virus (HCV) infection a very important factor in the development of HCC. As curative therapy is often ruled out due to the late detection of HCC, it would be attractive to find parameters which predict malignant transformation in HBV- and HCV-infected livers. This study has used comparative genomic hybridization (CGH) to analyse 26 HCCs (11 non-viral, nine HBV, six HCV) and 12 concurrent dysplasias (five non-viral, five HBV, two HCV). Frequent gain (> or =25% of all tumours) was detected, in decreasing order of frequency, on 8q (69%), 1q (46%), 17q (46%), 12q (42%), 20q (31%), 5p (27%), 6q (27%), and Xq (27%). Frequent loss (> or =25% of all tumours) was found, in decreasing order of frequency, on 8p (58%), 16q (54%), 4q (42%), 13q (39%), 1p (35%), 4p (35%), 16p (35%), 18q (35%), 14q (31%), 17p (31%), 9p (27%), and 9q (27%). Minimal overlapping regions could be determined at multiple locations (candidate genes in parentheses). Minimal regions of overlap for deletions were assigned to 4p14-15 (PCDH7), 8p21-22 (FEZ1), 9p12-13, 13q14-31 (RB1), 14q31 (TSHR), 16p12-13.1 (GSPT1), 16q21-23 (CDH1), 17p12-13 (TP53), and 18q21-22 (DPC4, DCC). Minimal overlapping amplified sites could be seen at 8q24 (MYC), 12q15-21 (MDM2), 17q22-25 (SSTR2, GH1), and 20q12-13.2 (MYBL2, PTPN1). A single high level amplification was seen on 5q21 in an HBV-related tumour. Aberrations appeared more frequent in HBV-related HCCs than in HCV-associated tumours (p=0.008). This was most prominent with respect to losses (p=0.004), specifically loss on 4p (p=0.007), 16q (p=0.04), 17p (p=0.04), and 18q (p=0.03). In addition, loss on 17p was significantly lower in non-viral cancers than in HBV-related HCC (p<0.001). Furthermore, loss on 13q was more prevalent in HCCs in non-cirrhotic livers (p=0.02), thus suggesting a different, potentially more aggressive, pathway in neoplastic progression. A tendency (p=0.07) was observed for loss on 9q in high-stage tumours; no specific changes were found in relation to tumour grade. A subset of the HCC-associated genetic changes was disclosed in the preneoplastic stage, i.e. liver cell dysplasia. This group of dysplasias showed frequent gain on 17q (25%) and frequent loss on 16q (33%), 4q (25%), and 17p (25%). The majority of the dysplasias with alterations revealed genetic changes that were also present in the primary tumour. In conclusion, firstly, this study has provided a detailed map of genomic changes occurring in HCC of viral and non-viral origin, and has suggested candidate genes. Loss on 17p, including the TP53 region, appeared significantly more prevalent in HBV-associated liver cancers, whereas loss on 13q, with possible involvement of RB1, was distinguished as a possible genetic biomarker. Secondly, CGH analysis of liver cell dysplasia, both viral and non-viral, has revealed HCC-specific early genetic changes, thereby confirming its preneoplastic nature. Finally, genes residing in these early altered regions, such as CDH1 or TP53, might be associated with hepatocellular carcinogenesis.
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PMID:Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias. 1100 97

1. Outcome from nonsurgical treatment is directly related to stage of hepatocellular cancer (HCC) and degree of liver function impairment. 2. Ablative percutaneous procedures, such as alcohol injection or radiofrequency thermal therapy, are most effective in the destruction of solitary tumors of 3 cm or less. 3. In most cases, nonsurgical treatments are not curative, but may slow tumor progression and can provide palliation. 4. Arterial embolization or chemoembolization has an antitumor effect, but it has not been shown to affect patient outcome. 5. Radiation therapy, chemotherapy, hormonal manipulation, and interferon have not been consistently effective in HCC. 6. Ablative procedures, embolization, and systemic chemotherapy should be avoided in patients with advanced cirrhosis.
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PMID:Nonsurgical treatment of hepatocellular carcinoma. 1108 79

Mutations of p53 as a tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported to occur with varying frequency in different geographic regions, which might be different etiology for HCC. Overexpressions of p53 (well known for its implications in mutations of the p53 gene), PCNA and alpha-fetoprotein (AFP) have been reported to be associated with carcinogenesis and/or tumor progression and poor prognosis in various types of cancer. To estimate the geographical difference of the p53 gene, PCNA and AFP in HCC, we examined 14 Japanese HCC cases, 8 Indonesian HCC cases, and 27 Indonesian chronic active hepatitis (CAH) or liver cirrhosis cases, using immunohistochemical approaches. Overexpression of p53 was identified in 37.5% of Japanese HCC, in 62.5% of Indonesian HCC and none in CAH. The mean PCNA Labeling Index of Japanese HCC, Indonesian HCC and CAH was detected in 48.6%, 30.4%, and 43.5%, respectively. AFP was detected in 35.7% of Japanese and 25% of Indonesian HCC. The rate of p53 overexpression in Indonesian HCC was as high as in HCC of southern part of China, which might share the similar etiology in both regions.
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PMID:Immunohistochemical study of P53, PCNA and AFP in hepatocellular carcinoma, a comparison between Indonesian and Japanese cases. 1141 97

Orthotopic liver transplantation (OLT) offers the only chance to eliminate both tumor and liver disease in patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumor progression while on the waiting list and recurrence after OLT are frequent. We undertook a large multicenter study to assess survival and related factors of recurrence after OLT. This retrospective study analyses data from 307 consecutive patients with HCC and cirrhosis treated with OLT between 1990 and 1997 in eight centers in Spain. OLT was indicated only for small (<5 cm) localized tumors. Five-year rates after OLT were 63% for survival, 58% for disease-free survival, and 21% for recurrence. Tumor diameter larger than 5 cm was associated with other tumor characteristics that were significant indicators of poor outcome (absence of capsule, three or more nodules, bilobularity, satellite nodules, and vascular invasion). However, in multivariate analysis, alpha fetoprotein (AFP) levels greater than 300 ng/mL (P = .04; P = .02) and macroscopic vascular invasion (P = .01; P = .0001) were the only factors independently associated with mortality and recurrence, respectively. OLT is indicated in patients with small HCCs who have low AFP levels and no macroscopic vascular invasion or extrahepatic disease. By increasing our ability for preoperative tumor imaging, we will achieve better selection of patients with HCC before OLT.
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PMID:Selection criteria for liver transplantation in early-stage hepatocellular carcinoma with cirrhosis: results of a multicenter study. 1167 86

Liver transplantation has become the best option in patients with decompensated cirrhosis and a small hepatocellular carcinoma. Indeed, because of the severity of cirrhosis, resection is usually impossible and in addition, transplantation provides survival rates close to those obtained in cirrhotic patients without malignancy (70 to 80% 3-year survival rate). In patients with a small hepatocellular carcinoma and compensated cirrhosis, both resection and transplantation can be performed. Because of the scarcity of donors, there have been reservations concerning transplantation in patients who otherwise could have undergone resection. However, there is increasing evidence that long-term results of transplantation are significantly superior to those of resection. Therefore, patients with a small hepatocellular carcinoma and compensated cirrhosis are increasingly considered as suitable candidates for transplantation. In contrast to cirrhotic patients with a small hepatocellular carcinoma, patients with large and/or multifocal tumors should no longer be transplanted because of a high rate of early recurrence and the accelerated course of tumor progression due to immunosuppression, both factors being the source of poor results. On rare occasions, hepatocellular carcinoma develops in patients without underlying liver disease. In such cases the tumor is usually recognized when it is large and symptomatic. The absence of underlying liver lesions offers the possibility of extended resection. However, in case of nonresectable (bilobar) tumors or limited recurrence after resection, transplantation may be considered due to the slow progression this subtype of hepatocellular carcinoma. Whatever the underlying liver parenchymal status, efforts should be made to reduce the risk of recurrence.
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PMID:Liver transplantation for hepatocellular carcinoma. 1194 82


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