Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated cryptogenic chronic active hepatitis

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe cryptogenic chronic active hepatitis (CAH), we tested sera from 17 corticosteroid-treated patients by an enzyme immunoassay. Specificity of the antibodies to HCV-encoded antigens was assessed by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only three patients (18%) with severe cryptogenic CAH had anti-HCV. Sera from two of these patients were reactive by recombinant immunoblot assay; the other sample produced an indeterminate reaction. The frequency of seropositivity in patients with cryptogenic disease was not statistically different from that in patients with autoimmune CAH (6%), hepatitis B surface antigen-positive CAH (9%), or alcoholic liver disease (0%), but it was significantly less than in those with posttransfusion CAH (18% versus 75%; P less than 0.01). Seropositive patients tended to have lower serum aspartate aminotransferase, gamma-globulin, and bilirubin levels than seronegative counterparts, and they did not have histologic features of confluent necrosis at initial assessment. Two of the three seropositive patients, both of whom had been reactive by recombinant immunoblot assay, entered remission during therapy, and one, with an indeterminate reaction, died of liver failure. We conclude that anti-HCV occurs infrequently in severe corticosteroid-treated cryptogenic CAH. Seropositive patients may have less severe inflammatory activity than seronegative counterparts. Cryptogenic disease may improve during corticosteroid treatment, a result suggesting an underlying immunologic disorder in some patients.     

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated autoimmune chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe autoimmune chronic active hepatitis, we tested sera from 85 cortico-steroid-treated patients by an enzyme immunoassay. Seropositive patients were assessed for specific antibodies to hepatitis C virus-encoded antigens by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only 5 of the 85 patients with autoimmune hepatitis (6%) were seropositive for anti-HCV, and only 2 of these patients were reactive by recombinant immunoblot assay. The frequency of seropositivity in autoimmune hepatitis was not significantly different from that in hepatitis B surface antigen-positive (9%) and cryptogenic (18%) disease, but it was significantly less than that in posttransfusion chronic active hepatitis (6% versus 75%; P less than 0.001). Two patients became seronegative after corticosteroid therapy; both had been nonreactive by recombinant immunoblot assay. Four of the seropositive patients entered remission during corticosteroid therapy, including three whose sera were nonreactive to virus-encoded antigens. We conclude that anti-HCV occurs infrequently in corticosteroid-treated severe autoimmune hepatitis and that antibodies detected by enzyme immunoassay may be nonreactive to hepatitis C virus-encoded antigens. Seropositive patients who are nonreactive by immunoblot assay may still respond to corticosteroid therapy and become seronegative during treatment.     

Duodenal mucosal ferritin in rheumatoid arthritis: implications for anaemia of chronic disease

Anaemia is a common feature of rheumatoid arthritis (RA) and other chronic diseases. Among the alterations in iron metabolism contributing to this effect is a decrease in intestinal iron absorption. The mechanism for this is unknown, but might involve a 'mucosal block' process similar to that proposed in iron overload, whereby increased expression of an enterocyte storage protein binds absorbed iron and prevents its transfer to the circulation. We examined the effect of disease-modifying therapy on ferritin expression in duodenal mucosa in RA to determine whether it may play a role in the 'mucosal block' process. Endoscopic small bowel biopsies were obtained from 11 patients with active RA both before, and 6 months after, a course of either gold or methotrexate (MTX). Mucosal ferritin levels in small bowel and stomach were measured by radio-immune assay. Duodenal mucosal ferritin decreased significantly following treatment (p <0.05). There were no changes in gastric mucosal ferritin. The fall in duodenal mucosal ferritin correlated with indices of disease activity at start of therapy, and the largest decreases were in those patients showing the best response to treatment in terms of a fall in inflammatory markers. Site-specific changes in mucosal ferritin may underlie the altered iron absorption observed in active inflammatory disease by modifying the enterocyte 'mucosal block'.      

2017年消化系统疾病主要临床进展

2017年国内外胃肠病学相关学会及专家制订或更新了诸多消化领域的指南及共识意见,其中国内消化系统疾病相关学组结合我国疾病的发病特点,制订了许多切合我国国情的临床共识,为临床工作的开展带来极大便利。本文主要从幽门螺杆菌感染、胃食管反流病、Barrett食管、炎症性肠病、病毒性肝炎、自身免疫性肝病及胰腺等疾病入手,全面详实的介绍消化领域疾病的国内外诊治进展,以期为消化内科医生诊疗疾病提供帮助。     

Detection of hepatitis B virus DNA sequences in liver in HBsAg seronegative patients with liver disease with and without anti-HBc antibodies

Excluding studies from Brechot and co-workers, little support has been found for a role of the hepatitis B virus in the pathogenesis of HBsAg seronegative patients with predominantly chronic liver diseases, including primary liver cancer. In this study liver DNA from 59 predominantly British patients (four cases with paired biopsies, 6-12 months apart) with different, mostly chronic, liver diseases was analysed by molecular hybridization. All were seronegative for HBsAg and serum hepatitis B virus DNA (dot blot hybridization) and their liver diseases were believed to be unrelated to hepatitis B virus infection. Hepatitis B virus DNA was detected in liver of 11 (18.6 per cent) patients; nine had episomal (3.2 Kb) DNA and eight had higher molecular weight bands suggesting integrated forms. Six patients were also seronegative for anti-HBc. Patients of UK and non-UK origin were equally represented. Hepatitis B virus DNA was detected in serum of six of nine patients tested using the polymerase chain reaction. The detection of hepatitis B virus DNA in liver and in serum by this assay in a significant proportion of patients with chronic liver disease, hitherto unsuspected of being hepatitis B virus-related, suggests a possible role for this virus in low- as well as high-prevalence countries.     

Detection of Helicobacter rodentium-like DNA in the liver tissue of patients with chronic liver diseases by polymerase chain reaction–denaturing gradient gel electrophoresis and DNA sequence analysis

Many Helicobacter spp. were isolated from the stomach, intestinal tract, and liver of different animals and humans. The association between Helicobacter spp. and hepatobiliary diseases, including hepatocellular carcinoma, was thoroughly examined, indicating a potential role of the bacteria in the progression toward cancer. In our work, we screened 97 liver biopsies from patients with chronic liver diseases for the presence of Helicobacter spp. DNA. With the use of genus-specific polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE) and subsequent sequencing, we found that the majority of Helicobacter spp. DNA detected was similar to Helicobacter rodentium DNA (71%). The DNA of other detected Helicobacter spp. was similar to Helicobacter pylori DNA. This is the first indication of H. rodentium-like DNA presence in human liver tissue. We also conclude that PCR–DGGE is a useful screening method for assigning species designation and heterogeneity.     

Celiac disease and autoimmune thyroid disease

Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders.     

Direct detection and amplification of Helicobacter pylori ribosomal 16S gene segments from gastric endoscopic biopsies.

Helicobacter pylori is an organism thought to play an important causative role in gastritis and peptic ulcer diseases. We have designed an RNA dot blot assay for the detection of H. pylori, using as probe a synthetic oligonucleotide complementary to its 16S rRNA. We have also used oligonucleotide primers, complementary to conserved sequences within bacterial ribosomal 16S genes, to amplify a H. pylori ribosomal 16S DNA fragment via the polymerase chain reaction (PCR). After determining the DNA sequence of this amplified H. pylori fragment, primers were designed for specific PCR amplification of H. pylori ribosomal 16S DNA sequences. Samples from clinical endoscopic biopsies were PCR amplified with universal 16S ribosomal primers to detect the presence of bacteria and with H. pylori-specific primers to uniquely detect H. pylori. Finally, by comparing the H. pylori-specific PCR assay to commonly used diagnostic tests, we demonstrate that the molecular technique of PCR amplification shows promising applications for the clinical detection of H. pylori.     

Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection

Hepatitis C is an infectious disease affecting the liver. Chronic infection can progress fibrosis and cirrhosis, liver failure or liver cancer. Helicobacter pylori (H. pylori) is a spiral bacterium infects the stomach of more than 50% of the human population worldwide. H. pylori DNA has been identified in human livers and has been implicated in chronic liver disease and liver cancer. The present work was aimed to study the histological and histochemical alterations in liver of HCV patients with or without H. pylori infection. Immunohistochemical detection of H. pylori showed positive reactivity in 62 biopsies out of 100 biopsies (38% HCV patients and 62% HCV patients coinfected with H. pylori). Histological examination of liver of HCV patients showed microvesicular and macrovesicular steatosis, lymphocytic infiltrations, fibrosis and cirrhosis. Cirrhotic nodules and impairment of hepatic parenchyma were common in HCV patients coinfected with H. pylori. HCV patients coinfected with H. pylori recorded higher NIC score and pronounced fibrosis stages than HCV patients. Glycogen and total proteins decreased in hepatocytes and cirrhotic nodules in HCV patients. Such decrease was marked in liver of HCV patients coinfected with H. pylori. So it is recommended to perform a complete analysis for H. pylori in HCV patients suggesting that it will help in therapy of this disease.     

Glycylprolyl-p-nitroanilidase in hepatobiliary disease

The serum activity of glycylprolyl-p-nitroanilidase (GPN) has been compared with isocitrate dehydrogenase and with alanine and aspartate aminotransferases in patients with hepatobiliary diseases, myocardial infarction and chronic inflammatory bowel disease. Serum GPN was markedly increased in all hepatobiliary diseases, especially secondary carcinoma and chronic alcoholic hepatitis, but no abnormal values were seen in patients with chronic inflammatory bowel disease. Slightly elevated GPN activities were noticed in a few cases of myocardial infarction. It is suggested that serum GPN would be useful for monitoring hepatic function, especially in the clinical trials of new drug.     

Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use

OBJECTIVE: The precise measurement of local tumor necrosis factor alpha (TNF-alpha) expression in tissue is important in understanding the pathogenesis of inflammatory bowel diseases (IBD). Real-time polymerase chain reaction (PCR) is a sensitive, versatile method and is becoming a commonly used tool for the quantification of gene expression. The aim of this study was to optimize the laboratory procedure for biopsy sampling, storage and calibration of result for TNF-alpha mRNA quantification with real-time PCR of colorectal biopsies. MATERIAL AND METHODS: Endoscopic biopsies from the colorectum were obtained from 18 patients with ulcerative colitis (UC), 11 patients with Crohn's disease (CD) and 18 normal controls. Optimization of procedures for real-time PCR performance was carried out. RESULTS: The transport medium, RNAlater, exhibited a high preservation effect against RNA degradation even after 8 days of storage at room temperature; one biopsy from each patient was sufficient for RNA extraction, cDNA synthesis and TNF-mRNA quantification. An assay was established with a technical reproducible sensitivity of 100 copies/microL. The observed interassay variations were 7.4 % coefficient of variation (CV) and 7.2 % CV in low and high TNF-alpha mRNA expression biopsies, respectively. TNF-alpha mRNA levels in colorectal biopsies from patients with either CD or moderate to severe UC were markedly increased, and 8 approximately 9-fold higher than those in healthy controls. CONCLUSIONS: This optimization improves the clinical use of real-time PCR for quantification of TNF-alpha gene expression in colorectal biopsies and provides a sensitive reproducible assay.     

The spectrum of chronic liver disease in renal transplant recipients.

Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries.     

幽门螺杆菌血清分型与上消化道疾病的关系

目的 探讨幽门螺杆菌(helicobacter pylori,Hp or H.pylori)分型与消化道不同疾病的关系。方法 入选198例Hp阳性的胃镜检查患者，采用免疫印迹法进行Hp的血清学分型，并取胃窦黏膜经HE染色观察胃窦黏膜病理组织学变化。结果 198例患者中检出HpI型菌株173例(87．4％)，Ⅱ型菌株25例(12．6％)。I型较II型Hp感染者胃镜下消化性溃疡、胃癌的比例更高，P=0.012；与胃炎组比较，十二指肠球部溃疡组、胃癌组的I型感染者更高（P值分别为0.026、0.048），而与胃溃疡组无显著差别(P=0.125)。病理组织学改变I型较II型Hp感染者的结果更为严重（P=0.038）。结论 临床上消化道疾病患者Hp感染以I型菌株最为多见。Hp感染的分型诊断有助于对胃、十二指肠疾病类型及病情的判断，I型菌株感染者需要更为积极的治疗。     

Association between celiac disease and vitiligo: A review of the literature

Celiac disease (CD) is an autoimmune intestinal disease caused by the intake of gluten-containing cereals and their products by individuals with genetic susceptibility genes. Vitiligo is a commonly acquired depigmentation of the skin; its clinical manifestation are skin patches caused by localized or generalized melanin deficiency. Both diseases have similar global incidence rates (approximately 1%) and are associated to similar diseases, including autoimmune bullous disease, inflammatory bowel disease, autoimmune thyroiditis, autoimmune gastritis, and type 1 diabetes. The relationship between CD and vitiligo has been reported in several studies, but their conclusions are inconsistent. Further, it has also been reported that a gluten-free diet (GFD) can improve the symptoms of immune-related skin diseases such as vitiligo. In this mini-review, we summarize and review the literature on the relationship between CD and vitiligo, assess the therapeutic significance of GFD for patients with vitiligo, and explore their possible physiopathology. We are hopeful that the information summarized here will assist physicians who treat patients with CD or vitiligo, thereby improving the prognosis.     

Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity

To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digestive disease with anemia

Anemia is often observed in digestive diseases such as gastroduodenal ulcers, esophageal varices, atrophic gastritis, malignant neoplasms, inflammatory bowel diseases, gastrectomy, malabsorption syndrome, and liver diseases. Anemia in these digestive diseases is caused by bleeding, iron deficiency, vitamin B12 deficiency including pernicious anemia, chronic inflammation (anemia of chronic disorders), malnutrition, hypersplenism. Especially in case of gastrointestinal bleeding, double balloon enteroscopy has been recently introduced to contribute to the diagnosis and treatment as well as gastroendoscopy and colonoscopy. In the treatment of digestive disease with anemia, it is important to treat digestive diseases appropriately. In treatment of patients with anemia of unknown origin, examinations about digestive diseases should be considered.     

Helicobacter pylori associated antral gastritis in peptic ulcer disease patients and normal healthy population of kashmir, India

Aim: To study the association of Helicobacter pylori infection with chronic antral gastritis in peptic ulcer disease patients and healthy population of Kashmir.Methods: 50 peptic ulcer patients (duodenal ulcer = 46, gastric ulcer = 2 and combined duodenal and gastric ulcer = 2) and 30 asymptomatic healthy volunteers were included in this study. Peptic ulcer was diagnosed on endoscopic examination. 4-6 punch biopsies were taken from gastric antrum in all the individuals and in case of gastric ulcer an additional biopsy was taken from the edge of the ulcer to exclude its malignant nature. Helicobacter pylori (H. pylori) organism was diagnosed using three different test methods, viz. Histology (using Giemsa Stain), Microbiology (Gram Stain) and Biochemistry (using one minute Endoscopy Room Test). Histological diagnosis of H. pylori was taken as the "gold standard" for the presence of H. pylori organism. Histological diagnosis of gastritis was made using Hematoxylin and Eosin Stain and the gastritis was classified as active chronic gastritis and superficial chronic gastritis.Results: Out of 30 peptic ulcer disease patients with associated antral gastritis, 27 (90%) were positive for H. pylori on histological examination (13 superficial chronic gastritis and 14 active chronic gastritis) whereas out of 8 healthy volunteers with histological evidence of chronic antral gastritis, H. pylori was observed in 7 individuals (87.50%) (4 active chronic gastritis and 3 superficial chronic gastritis).Conclusion: A highly significant association between H. pylori infection with chronic antral gastritis both in peptic ulcer disease patients and healthy volunteers of Kashmir was found in this study. Association between H. pylori infection and chronic gastritis was 90% in peptic ulcer group and 87.50% in healthy population (P<0.005).     

Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C

NAFLD (non-alcoholic fatty liver disease) is one of the most frequent chronic liver diseases worldwide. The metabolic factors associated with NAFLD are also determinants of liver disease progression in chronic HCV (hepatitis C virus) infection. It has been reported that, besides inducing hepatic fatty acid biosynthesis, LXR (liver X receptor) regulates a set of inflammatory genes. We aimed to evaluate the hepatic expression of LXRα and its lipogenic and inflammatory targets in 43 patients with NAFLD, 44 with chronic HCV infection and in 22 with histologically normal liver. Real-time PCR and Western blot analysis were used to determine hepatic expression levels of LXRα and related lipogenic and inflammatory mediators in the study population. We found that the LXRα gene and its lipogenic targets PPAR-γ (peroxisome-proliferator-activated receptor-γ), SREBP (sterol-regulatory-element-binding protein)-1c, SREBP-2 and FAS (fatty acid synthase) were overexpressed in the liver of NAFLD and HCV patients who had steatosis. Moreover, up-regulation of inflammatory genes, such as TNF (tumour necrosis factor)-α, IL (interleukin)-6, OPN (osteopontin), iNOS (inducible NO synthase), COX (cyclo-oxygenase)-2 and SOCS (suppressors of cytokine signalling)-3, was observed in NAFLD and HCV patients. Interestingly, TNF-α, IL-6 and osteopontin gene expression was lower in patients with steatohepatitis than in those with steatosis. In conclusion, hepatic expression of LXRα and its related lipogenic and inflammatory genes is abnormally increased in NAFLD and HCV patients with steatosis, suggesting a potential role of LXRα in the pathogenesis of hepatic steatosis in these chronic liver diseases.     

乙肝相关性肝病患者幽门螺杆菌感染的研究

目的研究慢性乙型肝炎(乙肝)、乙肝肝硬化、乙肝后肝癌等肝病患者幽门螺杆菌(Hp)感染情况。方法收集慢性乙肝、乙肝肝硬化、乙肝后肝癌等肝脏疾病患者273例,日期正常体检人群60例,采用免疫层析法检测患者血清中抗Hp抗体(Hp-IgG),定量PCR检测HBV DNA。结果乙肝相关性肝病患者Hp感染率73.3%,正常体检人群为40.0%,2组比较差异有统计学意义(P<0.01);慢性乙肝、乙肝肝硬化、乙肝后肝癌3组患者Hp感染率分别为62.7%、77.0%、79.7%,后二者Hp明显高于慢性乙肝患者(P<0.05);按病毒载量分级,HBV DNA阴性组Hp感染率低于HBV DNA阳性组,而阳性组按低、中、高分组,各组间Hp感染率分别为69.4%、65.0%、66.1%(P>0.05);乙肝肝硬化患者按Child-push分级后,A、B、C各级之间的Hp感染率分别为51.9%、63.4%、65.6%(P>0.05)。结论 Hp感染可能参与乙肝肝病患者肝脏损伤,显示Hp具有肝细胞毒性作用;肝硬化、肝癌感染率高于慢性乙型肝炎,提示Hp感染与慢性肝病疾病进展和肝癌的发生有一定相关性。     

Phytotherapeutic drugs in gastroenterology and hepatology

More and more patients are trying out herbal medicine. It is estimated that half of the population have used alternative products at least once in their live. Gastrointestinal diseases often require long-lasting treatments involving many side-effects that can impair the patient's motivation. The majority of persons with symptoms of the irritable bowel syndrome or chronic liver disease resort to non-conventional therapies. However, potential hepatotoxicity of herbal products should not be underestimated. In this article, we discuss herbal preparations in specific gastrointestinal and hepatological indications, concentrating on products that have been tested in randomized, controlled clinical trials. Effective symptomatic treatment of obstipation, irritable bowel and inflammatory bowel disease has been demonstrated with plant-derived preparations. On the other hand phytotherapeutic preparations can not be recommended at present for the treatment of cirrhosis or chronic viral hepatitis based on the available data.