bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does hepatitis C virus cause hepatocellular carcinoma?
Authors: Blum Hubert E. 
Published: March 2007

Background and Methods.
To detect potentially curable cases of hepatocellular carcinoma, outpatients with chronic hepatitis or compensated liver cirrhosis who were seen at the Center for Adult Diseases (Osaka, Japan) were examined periodically by means of ultrasonography and measurement of serum alpha-fetoprotein. Risk factors for hepatocellular carcinoma were identified with a Cox proportional-hazards model.

Results.
A total of 917 patients, 40 to 69 years old, were registered from May 1987 to March 1991. By the end of September 1991, liver cancer had developed in 54. The three-year cumulative risk of liver cancer was 12.5 percent for 240 patients with liver cirrhosis at enrollment and 3.8 percent for 677 patients with chronic hepatitis. Cox regression analysis showed that the risk of liver cancer was increased almost sevenfold in patients with hepatitis B surface antigen (rate ratio, 6.92; 95 percent confidence interval, 2.92 to 16.39) and fourfold in patients with hepatitis C antibody (rate ratio, 4.09; 95 percent confidence interval, 1.30 to 12.85). A high alpha-fetoprotein value at enrollment was also a risk marker for liver cancer.

Conclusions.
Patients with hepatitis C virus infection have a greatly increased risk of liver cancer. Further studies are required to clarify the roles of other risk factors, including drinking and smoking habits.
…And the bands play on
Authors: Schapiro Robert H. 
Published: March 2007

Injection sclerotherapy of bleeding oesophageal varices is undoubtedly beneficial but it is associated with a substantial complication rate, and variceal rebleeding is common during the treatment period before variceal obliteration is achieved. We aimed to find out whether endoscopic variceal banding ligation is safer and more effective. The two methods were compared in a randomised controlled trial of 103 patients (54 assigned to banding ligation, and 49 to injection sclerotherapy) of whom 21 (39) and 23 (47), respectively, had active bleeding at index endoscopy. Both treatments were highly effective in controlling active haemorrhage (91 and 92 respectively). Variceal obliteration was not achieved for 22 patients in each group, but among those whose varices were eradicated, banding ligation achieved obliteration more quickly than did sclerotherapy (mean 39 [SD 4] vs 72 [7] days, p = 0.004) and in fewer endoscopy sessions (3.4 [2.2] vs 4.9 [3.5], p = 0.006). Rebleeding was less common in the banding ligation group than in the sclerotherapy group (16 [30] vs 26 [53], p < 0.05). There was no difference in outcome between the groups, but 14 sclerotherapy patients were withdrawn from the trial (7 for orthotopic liver transplantation) compared with only 5 (1 for liver transplantation) in the banding ligation group (p < 0.05). Complication rates were similar in the two groups.
Variceal banding ligation is a safe and effective technique, which obliterates varices more quickly and with a lower rebleeding rate than injection sclerotherapy.
Hold that needle: Octreotide for acute variceal hemorrhage
Authors: Katkov William N. 
Published: March 2007

To compare octreotide with injection sclerotherapy in the treatment of acute variceal hemorrhage, patients admitted with gastrointestinal bleeding and oesophageal varices confirmed by endoscopy were randomised to receive either emergency sclerotherapy with 3% sodium tetradecyl sulphate or octreotide (50 μg intravenous bolus plus 50 μg per hr intravenous infusion for 48 hr). At the end of the study period (48 hr), the octreotide group also had sclerotherapy to obliterate the varices.
One hundred patients were recruited. Demographic features including the aetiology of portal hypertension and the Child-Pugh’s grading of the two groups were similar. Bleeding was initially controlled in 90% of patients by emergency sclerotherapy and in 84% by octreotide infusion (95% confidence interval 0-19.5, p = 0.55). There were no significant differences between the two groups in early (within 48 hr of randomisation) rebleeding (16% vs 14%), blood transfusion (3 units vs 3.51, hospital stay (5 days vs 6 days), or hospital mortality (27% vs 20%). No notable side-effects were associated with octreotide.
We conclude that octreotide infusion and emergency sclerotherapy are equally effective in controlling variceal haemorrhage.
Distinguishing primary and metastatic carcinomas of the liver: Immunohistochemical updates and reminders
Authors: Theise Neil O. 
Published: March 2007

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangio-carcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72 (B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18 (71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4 (83%) and mCEA (71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC, AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.
Hepatocyte paraffin 1 is a monoclonal antibody that has been developed specifically to react with hepatocytes in routine formalin-fixed and paraffin-embedded surgical pathology tissues. It results in a distinct, granular cytoplasmic staining of hepatocytes but fails to react with bile ducts and nonparenchymal liver cells. The antibody decorates a majority of hepatocellular carcinomas, including fibrolamellar variants. It fails to react with a wide variety of other adult malignancies, with the exception of focal staining in a few gastrointestinal malignancies, including a sub-population of gastric carcinomas.
Cholecystectomy protects against extrahepatic bile duct cancer: Is this a result of the removal of gallstones?
Authors: Walden David T. , Soloway Roger D. , Crowther Roger S. 
Published: March 2007

The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest.
All patients (62 734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26.3 expected for a standardised incidence ratio (SIR) of 0.88 (95% confidence interval [CI] 0.56-1.31). Ten years or more after operation there was a greater reduction of risk (SIR=0.27; 95% CI 0.06-0.80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR=1.15; 95% CI 0.91-1.44 overall, and 10 years or more after cholecystectomy SIR=0.98; 95% CI 0.66-1.40.
This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of cancer.
Is Hepatitis B Infection An Indication for Orthotopic Liver Transplantation? the Answer, My Friend, Is Blowin' in the Wind
Authors: Villamil Federico G. 
Published: March 2007

ABSTRACTBackground.The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti–hepatitis B surface antigen (anti–HBe) immune globulin is beneficial.Methods.We conducted a retrospective study at 17 European centers of 372 consecutive HBsAg–positive patients who underwent liver transplantation between 1977 and 1990. Recurrence of HBV infection was defined as the reappearance of HBsAg in serum.Results.For all 334 patients with follow–up data, the mean (± SE) three–year actuarial risk of recurrence of HBV was 50 ± 3 percent. The risk was 87 ± 4 percent among 163 patients with HBV–related cirrhosis. 32 ± 5 percent among 110 patients with cirrhosis related to hepatitis delta virus, 40 ± 16 percent among 14 patients with fulminant hepatitis delta infection, and 17 ± 7 percent among 39 patients with fulminant HBV infection (P<0.001). Among the patients with HBV–related cirrhosis, the risk of HBV recurrence was greatest (83 ± 8 percent) in those who were seropositive for HBV DNA at the time of transplantation and lowest (56 ± 7 percent) in those with neither HBV DNA nor hepatitis B e antigen detectable in serum. With respect to the use of passive prophylaxis with anti–HBs immune globulin, the risk of HBV recurrence was 75 ± 5 percent among the 67 patients given no immunoprophylaxis, 74 ± 5 percent among the 83 treated for two months, and 36 ± 4 percent among the 209 treated for six months or longer (P<0.001). In a multivariate analysis the predictors of a lower risk of HBV recurrence were the long–term administration of the immune globulin, hepatitis delta virus superinfection, and acute liver disease. For the entire study cohort, survival was 75 percent at one year and 63 percent at three years, but for those in whom HBV infection recurred, survival was 68 percent at one year and 44 percent at three years.Conclusions.In this retrospective study of HBsAg–positive patients, liver transplantation had better results in those who had fulminant hepatitis or delta virus superinfection. An absence of viral replication at the time of transplantation and long–term immunoprophylaxis were associated with a reduced risk of recurrent HBV infection and reduced mortality.
Genetic hemochromatosis and Wilson'S disease: Role for oxidant stress?
Authors: Britton Robert S. , Brown Kyle E. 
Published: March 2007

Hereditary haemochromatosis is characterised by iron overload that may lead to tissue damage. Free iron is a potent promoter of hydroxyl radical formation that can cause increased lipid peroxidation and depletion of chain-breaking antioxidants. We have therefore assessed lipid peroxidation and antioxidant status in 15 subjects with hereditary haemochromatosis and age/sex matched controls. Subjects with haemochromatosis had increased serum iron (24.8 (19.1-30.5) vs. 17.8 (16.1-19.5) μmol/L, P = 0.021) and % saturation (51.8 (42.0-61.6) vs. 38.1 (32.8-44.0), P = 0.025). Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were increased in haemochromatosis (0.59 (0.48-0.70) vs. 0.46 (0.21-0.71) μmol/l, P = 0.045), and there were decreased levels of the chain-breaking antioxidants alpha-tocopherol (5.91 (5.17-6.60) vs. 7.24 (6.49-7.80) μmol/mmol cholesterol, P = 0.001), ascorbate (51.3 (33.7-69.0) vs. 89.1 (65.3-112.9), P = 0.013), and retinol (1.78 (1.46-2.10) vs. 2.46 (2.22-2.70) μmol/l, P - 0.001). Patients with hereditary haemochromatosis have reduced levels of antioxidant vitamins, and nutritional antioxidant supplementation may represent a novel approach to preventing tissue damage. However, the use of vitamin C may be deleterious in this setting as ascorbate can have prooxidant effects in the presence of iron overload.
The RRR-alpha-tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection. Patients were divided into three groups: alcoholic liver diseases (n = 17; group A), hemochromatosis (n 17;group B) and Wilson's disease (n 12;group C). Lipidstandardized alpha-tocopherol levels were determined to neutralize differences due to hyperlipemia. The ratio of serum vitamin E to serum lipids (cholesterol, triglycerides, phospholipids) was highest in healthy controls and in patients in group A with cirrhosis and normal transaminases and bilirubin. Patients in group A with acute or chronic ethanol intoxication and high bilirubin levels had a 37% lower lipid-standardized vitamin E level than controls. Patients in group B with hemochromatosis, showing high serum iron (>180 μg/dl), a low free iron binding capacity (<8 μmol/l) and high ferritin-levels (>450 μg/l), had a 34% lower vitamin E/lipid ratio than healthy controls. No significant lowering of the vitamin E/lipid ratio was observed in the other patients in group B. A significant decrease (37%) in the vitamin E/lipid ratio was only detectable in patients with Wilson's disease (group C) showing high free serum copper (>10 μg/dl). The data support a role for free radicals in the pathogenesis of active liver diseases. © Journal of Hepatology.
Parenchymal FE and collagen gene expression: An iron-clad association?
Authors: Friedman Scott L. 
Published: March 2007

Background/Aims:
Liver fibrosis and cirrhosis represent common pathological findings in humans with iron overload. This study was undertaken to assess whether in vivo targeting of iron to liver parenchymal or nonparenchymal cells would differently affect collagen gene activity.

Methods:
Rats were treated with an iron diet or intramuscular injections of iron dextran, and in situhybridization analyses on liver samples were performed.

Results:
These iron treatments determined parenchymal or reticuloendothelial cell iron overload, respectively. The typical distribution of iron into different liver cells was documented by histochemistry and confirmed by in situ hybridization analysis with a ferritin L complementary RNA probe. In iron-fed rats, in situ hybridization analysis identified a signal for collagen type I messenger RNA into nonparenchymal cells in zones I and II. In rats with nonparenchymal cell iron overload, no activation of collagen gene expression was detected into or near iron-laden nonparenchymal cells. These findings were also confirmed by quantitative Northern blot analysis.

Conclusions:
The results of this study indicate that, regardless of the total hepatic iron burden, selective localization of iron into liver cells (i.e., parenchymal cells) is required for the activation of collagen gene during longterm iron overload in rodents.
The enigma of anti-neutrophil antibodies in ulcerative colitis primary sclerosing cholangitis: Important genetic marker or epiphenomenon?
Authors: Chapman Roger W. 
Published: March 2007

Background/Aims:
Perinuclear antineutrophil cytoplasmic antibodies (pANCA) were found at high frequency in patients with primary sclerosing cholangitis and ulcerative colitis. In this study, to accumulate further evidence for the importance of genetic factors in pathogenesis of inflammatory bowel disease, sera of patients with inflammatory bowel disease and primary sclerosing cholangitis and their unaffected family members were tested for pANCA.

Methods:
Three hundred twenty-seven sera from 11 families of patients with primary sclerosing cholangitis, 43 families of patients with ulcerative colitis, 11 families of patients with Crohn's disease, and 11 healthy families were tested for pANCA in immunofluorescence on cytospin slides with isolated neutrophils.

Results:
pANCA were found in 82% of the patients with primary sclerosing cholangitis and in 25% of their relatives. In ulcerative colitis, 70% of the patients and 30% of their relatives had pANCA. pANCA were found only in low titers in 27% of patients with Crohn's disease and in 6% of their relatives. pANCA were not detected in members of healthy families. Only 16% of the patients with ulcerative colitis and their families and none of the patients with primary sclerosing cholangitis and their families were completely negative for pANCA.

Conclusions:
These data show that pANCA may be a genetic marker in families of patients with ulcerative colitis and primary sclerosing cholangitis.
Macrophage function in cirrhosis and the risk of bacterial infection
Authors: Guarner Carlos , Runyon Bruch A. 
Published: March 2007

Background.
Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macro-phages play an important part in the host defense against infection because their Fcγ receptors recognize antibody-coated bacteria.

Methods.
We prospectively studied macrophage Fcγ-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers.

Results.
The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (±SE) of 47 ± 3 percent at 1 hour and 53 ± 3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P < 0.001). The impairment of macrophage Fcγ-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitized and heat-altered autologous erythrocytes was normal. In vitro recognition of IgG-sensitized red cells by monocytes from the patients was not significantly decreased. During a two-year follow-up period, 11 patients had severe bacterial infections, and in 4 they were fatal. The mean clearance of IgG-sensitized red cells in these 11 patients (half-time, 126.2 ± 22 hours) was significantly impaired, as compared with that in the 38 patients without severe infection (half-time, 32.2 ± 18 hours, P < 0.001).

Conclusions.
The function of macrophage Fcγ receptors is impaired in patients with alcoholic cirrhosis, and this impairment probably contributes to the high incidence of bacterial infections among such patients. (N Engl J Med 1994;331:1122-1128.)
Immunosuppression: Now we have choices
Authors: Sher Linda S. , Makowka Leonard 
Published: March 2007

Background.
Tacrolimus (FK 506), a macrolide compound isolated from a bacterium, is a potent immuno-suppressant with activity in solid-organ transplants. Most immunosuppressive regimens for liver transplantation are based on cyclosporine.

Methods.
We conducted an open-label, randomized, multicenter trial to compare the efficacy and safety of tacrolimus-based and cyclosporine-based immunosuppressive regimens for patients receiving a first liver transplant. A total of 478 adults and 51 children (≤12 years of age) were randomly assigned at the time of transplantation to receive tacrolimus (n = 263) or cyclosporine (n = 266) and were followed for one year. The primary end points were patient and graft survival at one year. The secondary end points were the incidence of acute rejection, corticosteroid-resistant rejection, and refractory rejection (continued rejection after two courses of corticosteroids and an intervening course of muromonab-CD3).

Results.
According to Kaplan-Meier analysis, actuarial patient-survival rates at day 360 were 88 percent for both the tacrolimus and cyclosporine groups (P = 0.85; 95 percent confidence interval for the difference, −5.4 to 6.6 percent), and graft-survival rates were 82 percent and 79 percent, respectively (P = 0.55; 95 percent confidence interval for the difference, −4.8 to 9.7 percent). Acute rejection occurred in 154 patients in the tacrolimus group and 173 patients in the cyclosporine group (P <0.002), corticosteroid-resistant rejection occurred in 43 and 82 patients, respectively (P <0.001), and refractory rejection occurred in 6 and 32 patients, respectively (P <0.001). Tacrolimus was associated with a higher incidence of adverse events requiring withdrawal from the study, primarily nephrotoxicity and neurotoxicity; 37 patients in the tacrolimus group and 13 in the cyclosporine group discontinued the study because of adverse events (P <0.001).

Conclusions.
After one year, immunosuppressive regimens based on tacrolimus and cyclosporine were comparable in terms of patient and graft survival. Tacrolimus was associated with significantly fewer episodes of acute, corticosteroid-resistant, or refractory rejection, but substantially more adverse events requiring discontinuation of the drug. (N Engl J Med 1994;331:1110-1115.)
Does interferon therapy for chronic hepatitis B reduce the risks of developing cirrhosis and hepatocellular carcinoma?
Authors: Lok Anna S. F. 
Published: March 2007

Objective:
To estimate the cost-effectiveness of interferon-α2B for the treatment of patients with chronic hepatitis B infection who are positive for hepatitis B e antigen (HBeAg).

Design:
Meta-analysis of nine randomized controlled trials and cost-effectiveness analysis, projecting the clinical and economic outcomes expected from changes in serologic markers of hepatitis B viral replication.

Data Sources:
MEDLINE search, expert panel opinion, hospital cost data, and adjusted physician charges.

Patients:
552 patients with confirmed chronic hepatitis B infection who were positive for HBeAg.

Intervention:
Interferon-α2b.

Measurements:
Lifetime incidence of cirrhosis and hepatocellular carcinoma; life expectancy; quality-adjusted life expectancy; and costs and marginal cost-effectiveness ratios from a societal perspective.

Results:
Interferon-α2b increases the likelihood of becoming negative for HBeAg from 9.1% to 45.6% (difference, 36.5%; 95% CI, 23.7% to 49.2%) and of becoming negative for hepatitis B surface antigen from 1.7% to 7.7% (difference, 6.0%; CI, 2.8% to 9.3%) in the first year. For a 35-year-old person with chronic hepatitis B who is HBeAg positive, our analysis suggests that interferono; α2b will increase life expectancy by 3.1 years or 3.4 quality-adjusted life-years and will decrease projected lifetime costs, even if future savings are discounted; thus, interferon-α2b is the dominant strategy. Even with the model biased strongly in favor of standard care, the marginal cost-effectiveness ratio of interferon did not exceed $12 000 per life-year gained.

Conclusions:
Interferon-α2b should prolong life and lower costs for patients with chronic hepatitis B who are HBeAg positive.
Nuclear magnetic relaxation of water in ionic‐liquid solutions: determining the kosmotropicity of ionic liquids and its relationship with the enzyme enantioselectivity
Authors: Zhao Hua , Song Zhiyan 
Published: March 2007

AbstractThe nuclear magnetic relaxations of water in ionic‐liquid (IL) solutions were examined at various IL concentrations in order to better understand their hydration behaviors (in terms of nuclear magnetic resonance (NMR) B′‐coefficients). From these B′‐values of ILs, the individual ion's B′‐coefficients were further calculated based on the additivity. These coefficients represent the hydration behavior (‘kosmotropicity’) of ILs in aqueous solutions. Using these data, a linear correlation was found between enzyme enantioselectivity in aqueous solution and the δ′ parameter (difference in NMR B′‐coefficients of anion and cation). In general, high enzyme enantiomeric ratios (E) could be achieved in solutions of ILs with high δ′ values. Copyright © 2007 Society of Chemical Industry