2型糖尿病对原发性肝癌发病的危险性分析

目的 明确糖尿病是否为原发性肝癌发病的危险因素.方法 采用病例对照研究的方法将原发性肝癌848例分为糖尿病组和非糖尿病组,分析糖尿病对原发性肝癌患病率的影响.结果 合并糖尿病的男性患者患原发性肝癌的OR值为11.78,女性患者OR值为8.21,男女性别间比较无显著性差异.糖尿病病程小于5年者患原发性肝癌的OR值为3.42,病程5～10年者OR值为13.83,病程大于10年者OR值为17.80.有糖尿病史但不嗜酒且无病毒性肝炎者患原发性肝癌的OR值为2.61,有糖尿病史合并病毒性肝炎但不嗜酒者OR值为11.84,有糖尿病史、嗜酒但无病毒性肝炎者OR值为5.51,有糖尿病史、嗜酒且合并病毒性肝炎者OR值为14.91,合并糖尿病的肝硬化患者发生原发性肝癌的OR值为2.38.结论 患糖尿病人群中原发性肝癌的发病率明显增加,且随着糖尿病病程增加,患病危险性增加,但在男女性别之间无明显差异.糖尿病是原发性肝癌的独立危险因素,与病毒性肝炎、嗜酒、肝硬化等因素之间有协同作用.     

Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis

BACKGROUND/AIMS: Several studies found hepatitis C (HCV) increases risk of Type II diabetes mellitus (DM). However, others found no or only sub-group specific excess risk. We performed meta-analyses to examine whether HCV infection does increase DM risk in comparison to the general population and in other sub-groups with increased liver disease rates including with hepatitis B (HBV). METHODS: We followed standard guidelines for performance of meta-analyses. Two independent investigators identified eligible studies through structured keyword searches in relevant databases including PubMed. RESULTS: We identified 34 eligible studies. Pooled estimators indicated significant DM risk in HCV-infected cases in comparison to non-infected controls in both retrospective (OR(adjusted)=1.68, 95% CI 1.15-2.20) and prospective studies (HR(adjusted)=1.67, 95% CI 1.28-2.06). Excess risk was also observed in comparison to HBV-infected controls (OR(adjusted)=1.80, 95% CI 1.20-1.40) with suggestive excess observed in HCV+/HIV+ cases in comparison to HIV+ controls (OR(unadjusted)=1.82, 95% CI 1.27-2.38). CONCLUSIONS: Our finding of excess DM risk with HCV infection in comparison to non-infected controls is strengthened by consistency of results from both prospective and retrospective studies. The excess risk observed in comparison to HBV-infected controls suggests a potential direct viral role in promoting DM risk, but this needs to be further examined.     

Risk factors for primary hepatocellular carcinoma in black and white Americans in 2000.

BACKGROUND & AIMS: The incidence of primary hepatocellular carcinoma (HCC) is greater in black Americans compared with white Americans. The aim of this study was to better define racial disparity in HCC patients in the United States. METHODS: We compared HCC risk factors in 158 black and 701 white HCC patients > or = 11 years of age in the Nationwide Inpatient Sample for 2000. RESULTS: Black HCC patients were younger than white patients (mean age, 54.1 +/- 17.1 vs. 65.1 +/- 13.7 y; P < .002). Sixty-two percent of black HCC patients were age 60 or younger, whereas 68% of white HCC patients were age 61 or older. Hepatitis C virus (HCV) (25.4%), diabetes (22.1%), alcohol (15.1%), cryptogenic cirrhosis (8.6%), and hepatitis B virus (HBV) (7.3%) were the most prevalent risk factors for HCC overall. HBV (22.8% vs 3.9%, P < .0001; adjusted odds ratio [OR], 5.3; 95% confidence interval [CI], 3.0-9.2), HCV (34.8% vs 23.3%, P = .0003; OR, 1.3; 95% CI .9-1.9), concurrent HBV and HCV (8.2% vs 1.7%, P < .0001; OR, 4.5; 95% CI, 1.9-10.4), HBV plus diabetes (2.5% vs .3%, P = .002; OR, 14.1; 95% CI, 2.2-88.2), and HCV plus diabetes (8.9% vs 4.4%, P < .02; OR, 2.3; 95% CI, 1.2-4.6) were more common in black HCC patients. There was no racial difference in the frequency of alcoholic and cryptogenic liver diseases and diabetes. CONCLUSIONS: Higher rates of HBV, HCV, concurrent HBV and HCV, and viral hepatitis associated with diabetes might explain the greater burden of HCC in black Americans.     

慢性丙型肝炎病毒感染者2型糖尿病流行病学调查

目的研究慢性丙型肝炎病毒感染者2型糖尿病的发病情况。方法对221例慢性丙型肝炎感染者(其中肝硬化72例)2型糖尿病发病情况进行调查,并与慢性乙型肝炎病毒感染者660例(其中肝硬化220例)2型糖尿病发病情况进行对照。结果慢性丙型肝炎感染者2型糖尿病的发病率为21.2%(47/221),高于慢性乙型肝炎感染者的10.9%(72/660)(P<0.02);丙型肝炎病毒致肝硬化2型糖尿病的发病率为30.6%(22/72),明显高于慢性丙型肝炎患者2型糖尿病发病率23.4%(35/149),(P<0.05),并明显高于对照组乙型肝炎病毒致肝硬化2型糖尿病的发病率11.3%(25/220),(P<0.05)。结论肝硬化是慢性丙型肝炎感染者发生2型糖尿病的危险因素;肝硬化和丙型肝炎病毒共同作用导致了2型糖尿病危险性的增加。丙型肝炎病毒致肝硬化2型糖尿病的发病率明显高于乙型肝炎病毒致肝硬化。     

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus

Background: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. Methods: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. Results: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV (P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV (P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. Conclusions: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations. Received: April 18, 2002 / Accepted: October 25, 2002 Reprint requests to: S. Kakumu     

Interaction of alcohol intake and cofactors on the risk of cirrhosis

Objective: Evaluation of the interaction between alcohol intake and cofactors [hepatitis B virus (HBV), hepatitis C virus (HCV), body mass index] and coffee consumption on the risk of cirrhosis. Design: Seven hundred and forty‐nine consecutive patients with chronic liver disease referring to units for liver or alcohol diseases in Italy during a 6‐months period. Teetotalers were excluded. The odds ratios (OR) for cirrhosis were evaluated using chronic hepatitis cases as the control group. Results: An alcohol intake of more than 3 units/day resulted associated with the likelihood of cirrhosis both in males (OR 4.3; 95% CI=2.5–7.3) and in females (OR 5.7; 95% CI=2.3–14.5). A multiplicative interaction on the risk of cirrhosis between risky alcohol intake and HBsAg or HCV‐Ab/HCV‐RNA positivity was observed. A reduction of cirrhosis risk was observed in subjects consuming more than 3 alcohol units/day with increasing coffee intake. The OR for the association with cirrhosis decreased from 2.3 (95% CI=1.2–4.4) in subjects drinking 0–2 cups of coffee/day to 1.4 (95% CI=0.6–3.6) in those drinking more than 2 cups/day. Conclusions: In subjects with an alcohol intake >3 units/day the coexistence of HBV or HCV multiplies the risk of cirrhosis. Coffee represents a modulator of alcoholic cirrhosis risk.     

Anticardiolipin antibodies in patients with liver disease

OBJECTIVE: Our aim was to test the hypothesis that anticardiolipin antibodies (aCL) may cause an antiphospholipid syndrome and thrombotic events in patients with liver disease. METHODS: aCL were measured in 116 healthy controls and 372 patients with liver disease of different stage and etiology: 136 cases secondary to hepatitis C virus (HCV) infection, 139 due to hepatitis B virus (HBV) infection, 69 with alcoholic liver damage, and 28 cryptogenic in origin. Prior thrombotic events were recorded. The results were related to age, gender, stage, severity, and etiology of the liver disease, as well as to the occurrence of organ- and nonorgan-specific autoantibodies. RESULTS: aCL were positive in 4.4% of controls and in 18.8% of patients (p < 0.0002). Patients with aCL were more frequently men with an advanced cirrhosis and simultaneous occurrence of anti-smooth-muscle antibodies (ASMA) in serum (p < 0.0006); their liver damage was often secondary to HBV (37.3%) or alcohol abuse (18.5%). At conditional logistic regression analysis, only the presence of ASMA (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.7-5.5, p = 0.0003), HBV (OR = 3.4, 95% CI 1.6-7.2, p = 0.0013), or alcoholic liver disease (OR = 5.3, 95% CI 2.3-12.2, p = 0.0001) were independently associated with aCL. Thrombosis was encountered in 24 patients (6.4%). At conditional logistic regression analysis, thrombosis was significantly associated with advanced age (OR = 1.07, 95% CI 1.0-1.1, p = 0.0094), development of hepatocellular carcinoma (OR = 17.8, 95% CI 1.6-196.0, p = 0.01), HBV etiology (OR = 6.3, 95% CI, 1.6-24.6, p = 0.0076), or cryptogenic liver disease (OR = 54.8, 95% CI 5-599.9, p = 0.001). Of the five patients with newly documented portal thrombosis during the follow-up, only one tested positive for aCL. CONCLUSIONS: In patients with nonautoimmune liver disease, aCL production is an epiphenomenon of the liver damage and is not associated with thrombotic complications. These data do not support the hypothesis that HCV is a cause of the antiphospholipid syndrome.     

Hepatitis B and C virus infection in Crohn's disease.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.     

Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy

BACKGROUND/AIMS: To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. METHODS: Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994-1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. RESULTS: Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95% confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5) and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection, obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95% CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. CONCLUSIONS: Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.     

More advanced hepatic fibrosis in hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis

BACKGROUND AND AIMS: We sought to assess whether Hispanics have more advanced hepatitis C virus (HCV)-related liver disease than non-Hispanic whites (NHW) and to identify contributory factors. PATIENTS AND METHODS: Patients were recruited from the Los Angeles county hepatitis clinic. Liver fibrosis and necroinflammation (NI) were assessed by the Ishak scoring system. Hepatic steatosis was graded as 0-4. RESULTS: A total of 232 patients were evaluated, 63 NHW and 169 Hispanic. Hispanics were older and had a higher prevalence of blood transfusion (40%vs 21%), obesity (body mass index > 30) (47%vs 21%), diabetes mellitus (DM) (16%vs 5%), and hepatic steatosis (79%vs 47%), p < 0.02. Independent predictors of hepatic steatosis were Hispanic ethnicity (odds ratio [OR] 3.8, 95% CI 1.7-8.7, p= 0.001) and obesity (OR 5.7, 95% CI 2.3-14.1, p= 0.0002). Compared with NHW, Hispanics also had higher fibrosis stage (3.3 +/- 2 vs 2.3 +/- 6.9, p= 0.001), NI grade (6.4 +/- 1.8 vs 5.6 +/- 1.6, p= 0.002), and faster fibrosis progression/yr (0.14 +/- 0.09 vs 0.09 +/- 0.07, p= 0.0002). Presence of DM (OR 2.9, p= 0.02), grade 1-2 hepatic steatosis (OR 2.3, p= 0.03), AST/ALT > 1 (OR 4.3, p= 0.01), NI grade (OR 1.7, p < 0.0001), age at biopsy (OR 1.1, p < 0.0001), and serum bilirubin (OR 5.4, p < 0.0001) were independent predictors of fibrosis stage > or =4. CONCLUSION: This study confirms that Hispanics have more advanced hepatic fibrosis than NHW. This is related to older age, higher NI grade, and greater prevalence of hepatic steatosis and DM.     

Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India

AIM: To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population. METHODS: A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied. RESULTS: The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06-91.98) for any HBV marker, 38.98 (19.55-77.71) for HBsAg positivity, 12.34 (2.84-53.61) for HBsAg negative and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02-14.71) for anti-HCV positive and HCV RNA positive, and 2.83 (1.51-5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61-97.19) and 35.03 (15.59-78.66) for any HBV marker; (ii) 39.88 (19.41-81.97) and 24.40 (10.60-56.18) for HBsAg positivity; and (iii) 12.10 (2.67-54.88) and 19.60 (3.94-97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti-HCV positivity and HCV RNA positivity [OR = 7.53 (2.73-20.78)] and for heavy alcohol use [OR = 3.32 (1.70-6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA positive [OR = 0.97 (0.11-8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55-4.53)]. CONCLUSIONS: Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.     

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case-control study

BACKGROUND: The risk factors for cholangiocarcinoma are poorly defined in the United States. We evaluated hepatitis C virus (HCV), hepatitis B virus (HBV), and liver cirrhosis as risk factors for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). METHODS: A case-control study in which cases were cholangiocarcinoma patients referred to the M.D. Anderson Cancer Center between 1992 and 2002 and controls were healthy individuals. Information about liver diseases, family history, diabetes, smoking, and alcohol consumption were collected on both groups. Blood from all participants was tested for HBV and HCV markers. RESULTS: We identified 246 cases (83 ICC and 163 ECC) and matched them to 236 controls. Compared with controls, ICC patients had a higher prevalence of anti-HCV antibodies (6.0%vs 0.8%, P=0.01), anti-HBc (9.6%vs 0%, P<0.0001), and heavy alcohol consumption (21.7%vs 3.8%, P<0.0001). The adjusted odds ratio and 95% confidence interval (CI) were 7.9 (95% CI 1.3-84.5), 28.6 (95% CI 3.9-1,268.1), and 5.9 (95% CI 2.1-17.4), respectively. Only heavy alcohol consumption was higher in patients with ECC than in controls (17.8%vs 3.8%, P=0.003). The prevalence of diabetes and smoking were not significantly different between cases (ICC or ECC) and controls. The prevalence of cirrhosis was higher in patients with ICC than those with ECC (24.1%vs 4.9%, P<0.0001). CONCLUSIONS: Liver cirrhosis and chronic HCV infection are possible risk factors for ICC but not ECC. Heavy alcohol consumption is a risk factor for both ICC and ECC.     

长期核苷(酸)类抗病毒治疗的乙型肝炎肝硬化患者肝癌发生相关因素研究

目的 探讨长期接受核苷酸抗病毒治疗的乙型肝炎肝硬化患者肝癌发生的相关危险因素。方法 2002年5月～2015年5月接受核苷(酸)类抗病毒治疗的乙型肝炎肝硬化患者417例,平均抗病毒治疗时间为(9.11±2.09)年。记录观察期内原发性肝癌发生情况。采用多元Logistics回归分析导致肝癌发生的危险因素。结果 在观察期内,本组417例乙型肝炎肝硬化患者发生原发性肝癌57例(13.7)%;肝癌组在有肝癌家族史、长期饮酒、Child-Pugh C级、未应用一线抗病毒药物、抗病毒治疗后血清HBV DNA水平仍大于20 IU/ml的比率显著高于未发生肝癌组(P<0.05);多因素Logistic分析显示存在肝癌家族史(OR=1.568,95%CI为1.074～2.289,P=0.020)、长期饮酒史(OR=1.791,95%CI为1.227～2.615,P=0.003)、Child-Pugh C级(OR=1.598,95%CI为1.095～2.333,P=0.016)、未应用一线抗病毒药物(OR=1.476,95%CI为0.997～2.168,P=0.047)和抗病毒治疗后血清HBV DNA水平仍未转阴(OR=1.480,95%CI为1.014～2.160,P=0.043)为肝癌发生的独立危险因素。结论 本研究经过长期随访观察,发现有肝癌家族史、长期饮酒、Child-Pugh分级C级、未应用一线抗病毒药物治疗和抗病毒治疗后血清HBV DNA仍大于20 IU/ml是导致乙型肝炎肝硬化患者发生肝癌的危险因素,选择一线抗病毒药物治疗、戒酒、改善肝功能状态可能减少肝癌的发生,值得认真对待。     

Habitual betel quid chewing as a risk factor for cirrhosis: a case-control study

Betel quid chewing, part of traditional Taiwanese culture, is common in 10%-20% of the human population worldwide. In this case-control study we assessed the independent and interactive role of habitual betel quid chewing and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on risk of cirrhosis. Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Univariate analysis indicated that betel quid chewing, HBsAg+, anti-HCV+, alcohol drinking, and smoking are significant risk factors for cirrhosis. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 3.56), HBsAg (OR 20.37), and anti-HCV (OR 31.43) are independent risk factors for cirrhosis. Most betel quid chewers habitually drink alcohol. Although our analysis indicates that betel quid chewing acts independently from alcohol as a risk factor for cirrhosis, the confounding effect of alcohol cannot be excluded entirely by our study. There was an additive effect of the interaction between betel quid chewing and the presence of either HBsAg or anti-HCV. Moreover, a higher risk of cirrhosis was associated with longer duration of betel quid chewing and greater amount of betel quid consumed (each p for trend <0.0001). In conclusion, betel quid chewing appears to be an independent risk factor for cirrhosis. There is an additive interaction between betel quid chewing and chronic HBV/HCV infection.     

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

AIM To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T, rs77416878 C/T, rs10488630 A/G, and rs2280714 T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B(CHB). n = 99; liver cirrhosis(LC), n = 131; hepatocellular carcinoma(HCC), n = 149] and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays. RESULTS Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin. CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.     

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.     

Incidence of hepatitis virus infection and severe liver dysfunction in patients receiving chemotherapy for hematologic malignancies

Hepatitis virus infection through virus reactivation has a high risk of mortality in patients with hematological malignancies receiving chemotherapy. We examined the incidence of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and severe liver dysfunction (alanine aminotransferase >ten times the normal upper limit and total bilirubin >5 mg/dl) during chemotherapy in 268 patients with hematological malignancies. Eight patients (3.0%) were infected with HBV and 22 patients (8.2%) were infected with HCV. One patient (0.4%) was infected with both HBV and HCV. HBV- or HCV-infected patients showed severe liver dysfunction at a significantly higher incidence than non-infected patients (11/31 (35.5%) vs. 0/237 (0%), p<0.0001). Furthermore, the incidence of severe liver dysfunction in HBV-infected patients was significantly higher than in HCV-infected patients (6/8 (75.0%) vs. 4/22 (18.2%), p<0.01). Three of eight HBV-infected patients were initially negative for hepatitis B surface antigen (HBsAg) by latex agglutination and became positive for HBsAg during chemotherapy. Furthermore, all three patients developed severe liver dysfunction and two developed fatal fulminant hepatitis. From an examination of the original stock of serum samples before chemotherapy, two patients were found to be positive for HBV-DNA by polymerase chain reaction (PCR). Although post-transfusion HBV infection was suspected in the one remaining patient, the cause of HBV infection could not be clarified due to the impossibility of examination in blood donors. Since HBV-infected patients develop severe liver dysfunction at a higher incidence than either patients not infected with virus or HCV-infected patients before chemotherapy for hematological malignancies, it is recommended that HBV-DNA should be tested by PCR to detect HBV marker-negative carriers and liver function tests should be carefully monitored.     

Mortality related to chronic hepatitis B and chronic hepatitis C in France: evidence for the role of HIV coinfection and alcohol consumption

BACKGROUND/AIMS: Mortality related to HCV and HBV infections was estimated in France. METHODS: A random sample (n=999) of death certificates was obtained from all death certificates listing HBV, HCV, hepatitis, liver disease, possible complication of cirrhosis, bacterial infection, HIV, or transplantation (n=65,000) in France in 2001. Physicians who reported the deaths were sent a questionnaire to identify how many deaths were related to HBV/HCV infection. Completed forms were independently analyzed by a panel of hepatologists. Death rates were estimated according to national population census data. RESULTS: Estimated annual number of deaths associated with HCV and HBV infection was 3618 and 1507, respectively (6.1 and 2.5 deaths per 100,000 inhabitants, respectively). Estimated number of deaths attributable to HCV or HBV infection was 2646 and 1327, respectively (4.5 and 2.2 deaths per 100,000 inhabitants, respectively). In the HCV infection group, 95 percent had cirrhosis; 33 percent had hepatocellular carcinoma (HCC). In the HBV infection group, 93 percent had cirrhosis; 35 percent had HCC. Eleven percent of deaths occurred in patients with HIV coinfection. Deaths related to HBV or HCV infection occurred at an earlier age in patients with a history of excessive alcohol consumption. CONCLUSIONS: In France, 4000-5000 deaths related to HCV and HBV infection occurred in 2001. Alcohol consumption and HIV infection were important co-factors. These data emphasize the need for ongoing, efficient public health programs that include screening, management, and counseling for HCV- and HBV-infected individuals.     

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach

BACKGROUND/AIMS: To evaluate by meta-analysis of available literature whether interferon (IFN) reduces the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV)-related Child A cirrhosis. METHODS: Three randomized controlled trials and 15 nonrandomized controlled trials, including 4614 patients and comparing IFN to no treatment, were selected. Data on the incidence of HCC in IFN treated and untreated patients were extracted from each study. Meta-analysis by the DerSimonian and Laird risk difference (RD) method was used to pool observations. RESULTS: A different incidence of HCC between treated and untreated cirrhotic patients was observed for HCV (overall RD -12.8%; 95% CI -8.3 to -17.2%, P < 0.0001) and HBV (overall RD -6.4%; 95% CI -2.8 to -10%, P < 0.001). In HCV-related cirrhosis, the rate of HCC development was lower in sustained responders to IFN than in untreated patients (overall RD -19.1%; 95% CI -13.1 to -25.2%, P < 0.00001), with low heterogeneity among trials (P=0.053), and also in nonresponders vs. untreated patients (overall RD -11.8%; 95% CI -6.4 to -19.1%, P < 0.0001), although with significant heterogeneity. Inconsistency among the studies was a major problem, both for HCV (chi2 = 58.16 with 13 DF; P < 0.0001) and HBV (chi2 = 26.4 with 6 DF; P = 0.0001) related cirrhosis, and also when follow-up was shorter than 60 months. Consistent results were only observed when assessing data from European reports: in this subgroup no preventive effect of HCC was shown for HBV (overall RD -4.8%; 95% CI -11.1-1.5%, P, not significant), and only a weak effect for HCV (overall RD -10%; 95% CI -5.9 to -14.2%; P < 0.0001). CONCLUSIONS: Literature data pooling suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to IFN. IFN does not seem to affect the rate of HCC in HBV-related cirrhosis.     

Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.