bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell mechanisms in the immunopathogenesis of viral hepatitis B and C
Authors: TSAI SL , HUANG SN 
Published: March 2008

ABSTRACTConsiderable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B and C. Both CD4+ and CD8+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and paediatric patients, and are more vigorous in patients with acute self‐limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also had a significant CD4+ T cell response to hepatitis C virus (HCV) antigens. These responses are also vigorous in acute hepatitis C with recovery than in those cases that evolve to chronic hepatitis C. In terms of human leucocyte antigen (HLA) class I‐restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated as the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within both HBsAg and HBcAg can be detected by sensitizing target cells with synthetic peptides. Similar to hepatitis B virus (HBV) infection, multi‐specific, HCV‐specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C are not yet clarified.
Epidemiological characteristics and risk factors of hepatocellular carcinoma
Authors: CHEN CHIEN‐JEN , YU MING‐WHEI , LIAW YUN‐FAN 
Published: March 2008

ABSTRACTHepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest‐to‐lowest ratio of 112.5 for males and 54.7 for females. The high‐risk populations are clustered in sub‐Saharan Africa and eastern Asia. The male‐to‐female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1‐albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N‐acetyltransferase 2 are associated with the development of HCC. A doseresponse relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S‐transferase M1 or T1, but not among those who have non‐null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene‐environment interactions are involved in the development of HCC in humans.
Hepatocellular carcinoma: Clinicopathological aspects
Authors: OKUDA KUNIO 
Published: March 2008

ABSTRACTThe histopathology and clinical picture of hepatocellular carcinoma (HCC) varies between individual patients and regions. These variations are perhaps due to differences in the genetic alterations that precede hepatocarcinogenesis. In this study, the clinicopathological features of HCC were compared between southern African blacks and Japanese, indicating large differences in the frequency of underlying cirrhosis, grade of cancer cell differentiation and clinical course. Intra‐abdominal bleeding and febrile, rapidly progressive HCC are more common among blacks. Such a difference is accounted for, in part, by frequent encapsulation of the tumour which is well differentiated, and grows slowly in an expanding fashion in Japan. Encapsulated HCC was not seen among the black patients studied. Other distinct clinicopathological types discussed in this paper include diffuse‐type HCC which is usually caused by multiple portal spread occurring almost simultaneously; the clinical course is fulminant. Sclerosing carcinoma is frequently associated with hypercalcaemia in the United States, but not in Japan. Fibrolamellar carcinoma is nearly non‐existent in Asia, whereas it is common among young adults in the West. Its prognosis is generally better than ordinary HCC. Hepatocellular carcinoma has a strong propensity to invade vessel and duct systems. Portal invasion does not produce distinct clinical signs although it may aggravate portal hypertension. Patients with tumour occlusion in the major portal vein may give rise to ischaemic hepatitis when blood pressure drops suddenly in the preterminal stage. Liver parenchyma develops submassive necrosis and clinically there is an acute rise in alanine aminotransferase (ALT). Invasion into a major hepatic vein and the inferior vena cava also occurs, but less frequently compared with portal invasion. The patient can live even with a tumour thrombus in the atrium crossing the tricuspid valves. Intraductal invasion causes acute jaundice as well as an occasional haemobilia with pain. We recently found that a distinct pathological type called ‘extrahepatic growth’ or ‘pedunculated HCC’ develops as a result of fusion of right‐sided adrenal metastasis of HCC and the liver, perhaps through the ‘adreno‐hepatic fusion’ which is rather common in cirrhotic livers.
Partial hepatic resection for hepatocellular carcinoma
Authors: CHEN MIIN‐FU , JENG LONG‐BIN 
Published: March 2008

ABSTRACTThis review summarizes the efficacy of the most common therapeutic option for hepatocellular carcinoma (HCC), partial hepatic resection, taking into account not only its antitumoural effect, but also its consequences on survival. Partial hepatic resection results in 5 year survival rates as high as 45% in more favourable subgroups having: small tumours, well‐differentiated tumours, unifocal tumours, a lack of vascular invasions, an absence of cirrhosis, and the nbrolamellar variant. Resection has been limited primarily by low resectability rates and recurrent disease. However, surgical resection in the form of partial hepatectomy is the preferred treatment for HCC. The early detection of tumours by screening high‐risk populations is crucial. During the 12 year period between 1983 and 1994, hepatic resections were carried out in 382 patients with HCC. One hundred and fifty‐three (40%) had HCC smaller than 5 cm in diameter. There were 294 male and 88 female patients, with an average age of 52.3 years. Among them, 45% had liver cirrhosis and 73% were positive for hepatitis B surface antigen. Two hundred and eighteen (57%) were positive for hepatitis C virus circulating antibodies (since 1991). Operative mortality was 3.9%. The overall survival rates at 1, 3 and 5 years were 71, 52 and 46%, respectively. Sex, cirrhosis, Child's staging, surgical procedure, blood loss, pathological pattern, presence of capsule, surgical margin and DNA ploidy appeared to be factors not related to prognosis. However, α‐fetoprotein level, size (whether less than or greater than 5 cm), and vascular invasion were factors which significantly affect survival.
Current therapeutic trends in therapy for chronic viral hepatitis
Authors: LIAW YUN‐FAN 
Published: March 2008

ABSTRACTHepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) are associated with clinically significant chronic infection that may lead to the development of cirrhosis or even hepatocellular carcinoma (HCC). Intervention at the earliest possible stage is needed to prevent such untoward sequelae. Currently, interferon (IFN) is the only approved and widely used agent for the treatment of these infections, including in HBV patients with precore mutant hepatitis or decompensated cirrhosis, but its efficacy is far from satisfactory. Corticosteroid priming has been shown to increase the efficacy of IFN therapy in HBV patients with low abnormal serum transaminase levels, but only a few responders will clear serum hepatitis Bs antigen (HBsAg). Ongoing randomized controlled trials of thymosin α1, lamivudine and famcyclovir have demonstrated encouraging preliminary results. Therapeutic vaccines, such as polypeptides with human leucocyte antigen (HLA)‐specific hepatitis B core antigen (HBcAg) epitopes, are under phase II/III clinical trial. For HDV infection, the use of IFN in the early phase of acute superinfection tends to prevent chronic progression. For HCV infection, IFN used at higher doses for a longer period of time is associated with a higher sustained response, but overall it is still not satisfactory. The combined use of ribavirin or corticosteroid priming may improve the effect of IFN therapy by enhancing the durability of the response. Interferon in the acute phase of HCV infection may also prevent chronic progression. There is evidence to suggest that IFN therapy, when associated with response, tends to reduce the risk of cirrhosis or HCC and prolongs survival. There is no doubt that satisfactory treatment of chronic viral infection will require more effective agents and demand optimal treatment strategies, many of which are yet to be found.
Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma
Authors: SUNG JUEI‐LOW 
Published: March 2008

ABSTRACTIn Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma‐derived vaccine 5 μg i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non‐vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7‐year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti‐hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post‐transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti‐HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.
Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment
Authors: TOMIMATSU MASAHIKO , ENDOU HITOSHI , TAKAHASHI HARUKI , IGA DAIJIRO , KATO YOSHIKAZU , TAMAI NORIO , NAKAJIMA HIROKO , OKANO AKIRA , MORI HARUKI , HISATOMI HISASHI 
Published: March 2008

ABSTRACTIn patients receiving interferon therapy for chronic hepatitis C, serum hepatitis C virus (HCV) RNA often reverts from an undetectable to a detectable form after completion of treatment. Detection of the negative strand of HCV‐RNA in liver tissue is regarded as an index of viral proliferation. Therefore, we investigated changes in the hepatic negative‐strand HCV‐RNA following interferon therapy to determine whether this parameter could predict the long‐term response to treatment. The subjects of this study were 27 patients with chronic active hepatitis C. Serum positive‐strand and hepatic tissue negative‐strand HCV‐RNA were detected using polymerase chain reaction. At the completion of interferon treatment, serum HCV‐RNA was not detected in 21 patients. One year following treatment it remained undetectable in 14 of these patients but it had reverted to a detectable form in seven. The 14 patients in whom hepatic negative‐strand RNA was not detected between 2 weeks and 12 months after treatment, had not relapsed after another year. In the 13 remaining patients, negative‐strand RNA was found in liver tissue and serum RNA either reverted to a detectable form or remained detectable throughout. From these findings, we conclude that the detection of negative‐strand HCV‐RNA in liver tissue 2 weeks after the completion of interferon therapy is useful for predicting the long‐term effect of therapy.
Abnormality in fatty acid composition of gastric mucosal phospholipids in patients with liver cirrhosis and its correction with a polyunsaturated fatty acid‐enriched soft oil capsule
Authors: MIYAMOTO AYUMU , WAKABAYASHI HIROYUKI , WATANABE AKIHARU 
Published: March 2008

ABSTRACTThe abnormal composition of the fatty acids in gastric mucosal phospholipids was examined in 11 patients with non‐alcoholic liver cirrhosis accompanied by gastritis and in 10 healthy subjects without liver disease and gastritis. The cases positive for serum anti‐Helicobacter pylori immunoglobulin G antibody were excluded. The arachidonic acid (AA, C20:4n‐6) contents of the two main components of phospholipid, the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions, in gastric biopsy specimens were significantly lower in the cirrhosis group, although PC and PE contents in gastric biopsy specimens were not altered. In the cirrhosis group, AA contents of the PC fractions in gastric biopsy specimens were significantly correlated with AA contents of plasma PC fractions and serum albumin levels. Soft oil capsules containing polyunsaturated fatty acid (PUFA) such as AA, eicosapentanoic acid (EPA, C20:5n‐3) and docosahexanoic acid (DHA, C20:6n‐3) were administered after each meal daily for 4 weeks to six cirrhotic patients and four control subjects, who were randomly selected from the patients and control subjects. After administration of PUFA‐enriched oil capsules, gastric mucosal AA contents of PC and PE fractions were significantly improved almost to the control levels. In three cirrhotic patients with severe or mild gastritis whose gastric mucosal lesions were endoscopically shown to have responded to PUFA‐enriched oil capsules, AA contents of plasma PC and PE fractions before administration were much lower than in the remaining three cirrhotics that did not respond to the PUFA‐enriched oil capsules, but significantly improved to the control levels after administration of oil capsules. The results demonstrate that administration of PUFA‐enriched soft oil capsules increased AA contents of the phospholipids in gastric mucosa and thus improved gastric mucosal lesions endoscopically in cirrhotic patients with gastritis.
Virulence‐associated genes as markers of strain diversity in Helicobacter pylori infection
Authors: ITO AKIRA , FUJIOKA TOSHIO , KODAMA KAORU , NISHIZONO AKIRA , NASU MASARU 
Published: March 2008

ABSTRACTTo establish a marker of strain diversity of Helicobacter pylori, a genetic examination was performed based on the detection rates by PCR of cagA and vacA, which are known to be virulence‐associated genes. The test strains were obtained from 70 patients suffering from gastric ulcer (GU), 82 patients with duodenal ulcer (DU) and 48 patients with gastritis (GS). Fragments located in the three different regions of vacA were amplified; V1 being the upstream portion, V2 the mid‐portion and V3 the downstream portion. For cagA, the detection rates were 70% for GU, 79% for DU and 50% for GS, showing a significantly higher rate for DU than for GS (P= 0.0005). With V1, the detection rates were 90% for GU, 90% for DU and 69% for GS, giving a significantly higher rate for GU than for GS (P= 0.0036) and also giving a significantly higher rate for DU than for GS (P= 0.0019). With V2, the detection rates were 60% for GU, 70% for DU and 44% for GS, giving a significantly higher rate for DU than for GS (P= 0.0024). The differences in vacA gene polymorphism were closely related to the evidence of gastroduodenal ulcers in H. pylori infection. Furthermore, the detection rates of cagA and polymorphisms of vacA by PCR could be used as markers of strain diversity in H. pylori‐induced gastroduodenal ulcer.
REVIEW: The surgical management of ulcerative colitis
Authors: FRIZELLE FA , BURT MJ 
Published: March 2008

ABSTRACTThe treatment of ulcerative colitis requires careful review of the medical and surgical options. The surgical procedure of choice is proctocolectomy with ileal pouch‐anal anastomosis. This procedure removes the diseased mucosa, effectively curing the disease whilst maintaining the normal route of defecation and continence. Other surgical options that may be considered in selected patients include proctocolectomy with either a Brooke ileostomy or a Kock pouch, and abdominal colectomy with ileorectal anastomosis. The choice of operation requires consideration of the advantages and disadvantages of a particular procedure and must be tailored to an individual patient's needs and circumstances.
Thiolmethyltransferase activity in the human colonic mucosa: Implications for ulcerative colitis
Authors: MOORE JAMES WE , BABIDGE WENDY J , MILLARD SUE H , ROEDIGER WILLIAM EW 
Published: March 2008

ABSTRACTUlcerative colitis is associated with a selective reduction of n‐butyrate oxidation by the colonic epithelial cells although the reason for this has been unclear. Colonic epithelial cell n‐butyrate oxidation can be inhibited in vitro by incubation with sulphide but the role of mucosal detoxification of sulphide in the metabolic welfare of the colonic mucosa has not been examined. This study aimed to assess the role mucosal detoxification of sulphide by thiolmethyltransferase (TMT)‐mediated methylation may play in protecting the healthy colonic mucosa from the adverse effects of luminal sulphide. Colonic epithelial cell suspensions from healthy human proximal (n= 9) and distal colon (n= 10) were incubated in the presence of 14C‐labelled n‐butyrate (5 mmol/L) alone, butyrate plus sodium hydrogen sulphide (NaHS) (1.5 mmol/L), or butyrate plus NaHS plus S‐adenosyl‐methionine 1,4 butane disulphonate (SAMe) (5 mmol/L). Study end points were metabolic performance (14CO2 production) and mucosal TMT activity. Incubation with NaHS induced a significant inhibition of 14CO2 production compared with control incubations (P < 0.001) which was similar for proximal and distal colonic cell suspensions. S‐adenosyl‐methionine 1,4 butane disulphonate reversed this effect completely in proximal but not in distal cell incubations, suggesting a greater susceptibility of the distal colon to the sulphide effect. Although median whole mucosal TMT values did not differ between proximal and distal colonic mucosa, a non‐normal distribution of distal TMT values was observed. However, neither the degree of sulphide inhibition of control 14CO2 production nor the degree to which SAMe reversed this inhibition correlated with whole mucosal TMT activity. The study concluded that regional variation exists in TMT activity in the human colon but whilst methylation appears to protect colonic epithelial cells against sulphide‐induced inhibition of n‐butyrate oxidation, this cannot be directly correlated with mucosal TMT activity.
Helicobacter pylori: From art to a science
Authors: HUNT RH , LAM SK 
Published: March 2008

ABSTRACT Helicobacter pylori infection is widely prevalent especially in developing countries. Increasing knowledge of the pathophysiology associated with H. pylori is leading to an understanding of the mechanisms of mucosal inflammation and gastritis and how this leads to peptic ulcer disease, gastric mucosal associated lymphoid tissues (MALT), lymphoma and gastric cancer. More accurate diagnostic testing for the infection is now possible with both endoscopic and non‐endoscopic tests to identify patients most appropriate for eradication therapy. Modern treatments tend to overcome the problems of metronidazole resistance and compliance seen with two week bismuth triple therapy and widely studied is a proton pump inhibitor given with clarithromycin and amoxicillin or metronidazole for one week. These achieve amongst the highest eradication rates and have also been shown to be cost effective. This paper reviews these recent advances and addresses areas of clinical interest and future directions.
CASE REPORT: Insulin ‐ like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia
Authors: YAMAGUCHI MASAKO , KAMIMURA SEIICHIRO , TAKADA JUNICHI , IWATA KAORU , IIDA TAKESHI , KOBAYASHI KAZUO , NAKANO HAJIME , OKADA YASUHIRO , FUJIIMI SATORU , SOHDA TETSURO , HIZUKA NAOMI 
Published: March 2008

ABSTRACTThis case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin‐like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour‐associated IGF2.