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Alcoholic Hepatitis

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28321. Zonation of hepatic cytochrome P-450 expression and regulation. Full Text available with Trip Pro

Zonation of hepatic cytochrome P-450 expression and regulation. The CYP genes encode enzymes of the cytochrome P-450 superfamily. Cytochrome P-450 (CYP) enzymes are expressed mainly in the liver and are active in mono-oxygenation and hydroxylation of various xenobiotics, including drugs and alcohols, as well as that of endogenous compounds such as steroids, bile acids, prostaglandins, leukotrienes and biogenic amines. In the liver the CYP enzymes are constitutively expressed and commonly also (...) induced by chemicals in a characteristic zonated pattern with high expression prevailing in the downstream perivenous region. In the present review we summarize recent studies, mainly based on rat liver, on the factors regulating this position-dependent expression and induction. Pituitary-dependent signals mediated by growth hormone and thyroid hormone seem to selectively down-regulate the upstream periportal expression of certain CYP forms. It is at present unknown to what extent other hormones

1998 Biochemical Journal

28322. Quantitative assessment of fibrosis and steatosis in liver biopsies from patients with chronic hepatitis C Full Text available with Trip Pro

Quantitative assessment of fibrosis and steatosis in liver biopsies from patients with chronic hepatitis C Hepatic fibrosis is one of the main consequences of liver disease. Both fibrosis and steatosis may be seen in some patients with chronic hepatitis C and alcoholic liver disease (ALD).To quantitate fibrosis and steatosis by stereological and morphometric techniques in patients with chronic hepatitis C and compare the results with a control group of patients with ALD. In addition (...) , to correlate the quantitative features of fibrosis with the Ishak modified histological score.Needle liver biopsies from 86 patients with chronic hepatitis C and from 32 patients with alcoholic liver disease (disease controls) were analysed by stereological and morphometric analyses using the Prodit 5.2 system. Haematoxylin and eosin and Picro-Mallory stained sections were used. The area fractions (A(A)) of fibrosis, steatosis, parenchyma, and other structures (bile duct and central vein areas) were

2001 Journal of Clinical Pathology

28323. The epidemiology of hepatitis C in a UK health regional population of 5.12 million Full Text available with Trip Pro

a correlation between high alcohol intake and fibrosis score. Multivariate analysis showed fibrosis to be associated with age over 40, past evidence of hepatitis B virus infection, and higher necroinflammatory grade but not with sex, viral genotype, maximum known alcohol intake, estimated duration of infection, or mode of transmission. Twelve (7.8%) of 153 patients who received interferon therapy had sustained serum virus clearance. Sixty six patients have died during the follow up period, 31 with a liver (...) The epidemiology of hepatitis C in a UK health regional population of 5.12 million The epidemiology and natural history of hepatitis C virus (HCV) infection in the UK are uncertain. Previous reports are from small or selected populations such as blood donors or tertiary referral centres.To study the epidemiology and natural history of HCV infection.Prospective study incorporating five centres within the Trent region. Patients were managed and followed up according to a commonly agreed

2001 Gut

28324. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Full Text available with Trip Pro

Estimating future hepatitis C morbidity, mortality, and costs in the United States. This study estimated future morbidity, mortality, and costs resulting from hepatitis C virus (HCV).We used a computer cohort simulation of the natural history of HCV in the US population.From the year 2010 through 2019, our model projected 165,900 deaths from chronic liver disease, 27,200 deaths from hepatocellular carcinoma, and $10.7 billion in direct medical expenditures for HCV. During this period, HCV may (...) lead to 720,700 years of decompensated cirrhosis and hepatocellular carcinoma and to the loss of 1.83 million years of life in those younger than 65 at a societal cost of $21.3 and $54.2 billion, respectively. In sensitivity analysis, these estimates depended on (1) whether patients with HCV and normal transaminase levels develop progressive liver disease, (2) the extent of alcohol ingestion, and (3) the likelihood of dying from other causes related to the route of HCV acquisition.Our results

2000 American Journal of Public Health

28325. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C Full Text available with Trip Pro

Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased hepatic fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease-that is, related to visceral adiposity and obesity.The effect of a three month weight reduction programme on liver biochemistry and metabolic (...) parameters was examined in 19 subjects with steatosis and chronic hepatitis C. Paired liver biopsies were performed in 10 subjects, prior to and 3-6 months following the intervention, to determine the effect of weight loss on liver histology.There was a mean weight loss of 5.9 (3.2) kg and a mean reduction in waist circumference of 9.0 (5.0) cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p

2002 Gut

28326. Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells. Full Text available with Trip Pro

Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells. Acetaldehyde, the major active metabolite of alcohol, induces the activation of hepatic stellate cells (HSC), leading to over-production of alpha1(I) collagen and ultimately causing hepatic fibrosis. The underlying mechanisms of this process remain largely unknown. Transforming growth factor-beta1 (TGF-beta1 (...) ) is a potent inducer of alpha1(I) collagen production. Accumulating evidence has shown a potential role for TGF-beta1 in alcohol-induced hepatic fibrogenesis. The aims of this study were to determine the effect of acetaldehyde on TGF-beta signalling, to elucidate the underlying mechanisms as well as to evaluate its role in expression of alpha1(I) collagen gene in cultured HSC. It was hypothesized that acetaldehyde activated TGF-beta signalling by inducing the expression of elements in the TGF-beta signal

2002 Biochemical Journal

28327. The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C Full Text available with Trip Pro

The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C Chronic hepatitis C virus (HCV) infection is frequently associated with elevated markers of iron stores. Recessively inherited mutations in the HFE gene are responsible for iron accumulation in most cases of hereditary haemochromatosis and may have a role in HCV infection. They may also be associated with progressive liver fibrosis although this remains controversial.To assess (...) the prevalence of HFE mutations in Scottish HCV infected patients and to explore the effect of the carrier state on serum and liver iron stores, and the severity of liver disease.A total of 164 patients with antibodies to HCV who underwent liver biopsy were assessed prospectively.Each patient was screened for HFE mutations (Cys282Tyr and His63Asp). Iron markers were assessed in serum (ferritin, transferrin saturation) and on liver biopsy (stainable iron, liver iron concentration (LIC) and hepatic iron index

2002 Gut

28328. Risk Factors for Hepatitis C Virus Infection Among Homeless Adults Full Text available with Trip Pro

to be HCV-infected. Similar results were found for those who had been hospitalized for a mental health problem. Among non-injection drug users and persons in the total sample, those who reported lifetime alcohol abuse were more likely than those who did not to be HCV infected. Controlling for sociodemographic characteristics, multiple logistic regression analyses revealed IDUs have over 25 times greater odds of having HCV infection than non-IDUs. HCV infection was also predicted by older age, having (...) started living on one's own before the age of 18, and recent chronic alcohol use. Males and recent crack users had about one and a half times greater odds of HCV infection when compared to females and non-chronic crack users.Targeted outreach for homeless women and their partners, including HCV testing coupled with referrals to HCV and substance abuse treatments, may be helpful.

2002 Journal of General Internal Medicine

28329. Heavy drinking greatly increases the risk of cirrhosis in patients with HCV hepatitis Full Text available with Trip Pro

Heavy drinking greatly increases the risk of cirrhosis in patients with HCV hepatitis 11709504 2001 12 28 2018 11 13 0017-5749 49 6 2001 Dec Gut Gut Heavy drinking greatly increases the risk of cirrhosis in patients with HCV hepatitis. 750-1 Day C P CP Centre for Liver Research, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. c.p.day@ncl.ac.uk eng Journal Article England Gut 2985108R 0017-5749 AIM IM Alcoholism complications Disease Progression Female Hepatitis C, Chronic

2001 Gut

28330. Hepatitis C virus infection among Alaskan drug users. Full Text available with Trip Pro

Am J Public Health 1254074 0090-0036 AIM IM Adult Alaska epidemiology Female Hepatitis C epidemiology transmission Humans Male Prevalence Substance Abuse, Intravenous complications 1997 11 14 1997 11 14 0 1 1997 11 14 0 0 ppublish 9357367 PMC1381148 J Infect Dis. 1991 Oct;164(4):820-1 1910071 J Acquir Immune Defic Syndr. 1992;5(8):803-9 1517965 N Engl J Med. 1992 Dec 31;327(27):1899-905 1280771 Med Clin North Am. 1996 Jan;80(1):1-14 8569290 Arch Intern Med. 1993 Sep 13;153(17):2025-30 8357288 (...) Medicine (Baltimore). 1995 Jul;74(4):212-20 7623656 Am J Drug Alcohol Abuse. 1993;19(2):219-38 8484358

1997 American Journal of Public Health

28331. Efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological test performance in patients with hepatic cirrhosis : results of a randomised trial. (Abstract)

and/or hepatitis B, alcohol abuse and other causes. Patients randomised to active treatment, received oral L-carnitine 6 g/day in two divided doses for 4 weeks. Diagnosis of SHE was based on psychometric tests (subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Neuropsychological Test Battery) carried out at beginning and end of study. Serum ammonia levels were measured before treatment and weekly thereafter.A total of 27 patients completed the study. Sixteen patients received L (...) Efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological test performance in patients with hepatic cirrhosis : results of a randomised trial. To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and subclinical hepatic encephalopathy (SHE).Randomised, parallel group, controlled trial.The study enrolled 31 patients with hepatic cirrhosis resulting from hepatitis C

2002 Clinical drug investigation Controlled trial quality: uncertain

28332. Prevalence and genotypes of hepatitis C virus infection among drug addicts and blood donors in Thailand. (Abstract)

Prevalence and genotypes of hepatitis C virus infection among drug addicts and blood donors in Thailand. Hepatitis C virus (HCV) is an infectious agent that has the potential to cause chronic liver disease, cirrhosis and hepatocellular carcinoma. We determined the prevalence and genotypes of HCV infection among groups of drug addicts: intravenous drug users (n = 134), methamphetamine users (n = 100), inhaled-drugs users (n = 19) and alcoholics (n = 50); a group of blood donors acted (...) as a control. The control group consisted of 179 randomly-selected anti-HCV positive samples: these were subjected to HCV RNA screening and genotyping. The anti-HCV test was performed by ELISA: HCV RNA screening was by nested RT-PCR that employed primers from the 5' noncoding region. The genotype assay was based upon analysis of the 5' NCR amplified sequences and RFLP. Hepatitis C virus was highly prevalent among all groups of drug addicts (12-70%). In 2000. among the new blood donors (n = 66,340

2002 Southeast Asian Journal of Tropical Medicine and Public Health

28333. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. (Abstract)

Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. Several studies found a high incidence rate of neuro-psychiatric complications during long-term therapy with interferon alpha (IFNalpha), e.g. slowness, severe fatigue, hypersomnia, lethargy, depressed mood, mnemonic troubles, irritability, short temper, emotional lability, social withdrawal, and lack of concentration. The aim of this study was to examine the incidence of depressed mood and major (...) depression in patients who were treated with IFNalpha.30 patients, affected by chronic active C-hepatitis, have been evaluated at baseline and 3 months after IFNalpha treatment. The evaluation consisted of psychometric assessments employing the DSM-IV criteria and the Montgomery Asberg Depression Rating Scale (MADRS).At end-point, 40.7% of the patients suffered from a full blown major depression, according to the DSM-IV criteria for major depression. IFNalpha treatment induced a significant increase

2002 Journal of Affective Disorders

28334. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). (Abstract)

chronic hepatitis C virus (HCV) infection. In 2001, deaths due to ESLD (14.3%) were significantly more frequent than in 1995 (1.5%; P < 0.01) and 1997 (6.6%; P < 0.01). During this interval, the prevalence of hepatocellular carcinoma as a cause of death increased (1995, 4.7%; 1997, 11%; 2001, 25%; P < 0.05), as did alcohol consumption (P < 0.01).In the post-HAART era, ESLD due to HCV is a growing cause of mortality in HIV-infected patients. Increased longevity attributable to HAART, and a higher (...) Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). To determine mortality due to end-stage liver disease (ESLD) in a nationwide cohort of HIV-infected patients 5 years after the introduction of highly active antretroviral therapy (HAART) and to compare this with that observed before and during the early years of HAART.and methods: All departments of internal medicine and infectious diseases from the GERMIVIC Study Group prospectively

2003 AIDS

28335. Testing, referral, and treatment patterns for hepatitis C virus coinfection in a cohort of veterans with human immunodeficiency virus infection. Full Text available with Trip Pro

-positive patients, 43% were coinfected with hepatitis C virus. Of these, 88 (30%) reported current alcohol consumption. Only one-third were counseled to reduce or stop alcohol consumption. Coinfected patients with indications for hepatitis C treatment had a high rate of contraindications, including both medical and psychiatric comorbidities. Of the 65 patients with indications for hepatitis C therapy and free of contraindications for treatment, only 18% underwent liver biopsy and 3% received IFN (...) . Although treatment indications are common in this population, contraindications are also common. Health care providers are often unaware of alcohol consumption that may accelerate the course of hepatitis C, increase the risk of hepatocellular carcinoma, and reduce treatment efficacy.

2003 Clinical Infectious Diseases

28336. Hepatitis C virus and human immunodeficiency virus coinfection in an urban population: low eligibility for interferon treatment. Full Text available with Trip Pro

Hepatitis C virus and human immunodeficiency virus coinfection in an urban population: low eligibility for interferon treatment. One hundred eighty human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients were prospectively evaluated for suitability for interferon and ribavirin therapy. Of the 149 patients with chronic HCV infection who completed the evaluation, 44 (30%) were eligible for treatment and 105 (70%) were ineligible, with the main barriers being missed (...) clinic visits, active psychiatric illness, active drug or alcohol use, decompensated liver disease, or medical illness.

2003 Clinical Infectious Diseases

28337. Isoniazid hepatotoxicity among drug users: the role of hepatitis C. Full Text available with Trip Pro

Isoniazid hepatotoxicity among drug users: the role of hepatitis C. The incidence of and risk factors associated with hepatotoxicity in patients with chronic hepatitis have not been systematically studied. Therefore, we conducted a prospective study that included former drug users who were treated with isoniazid for latent tuberculosis infection. Of 415 patients, 20 (4.8%; 95% confidence interval [CI], 3-7.4) had hepatotoxicity diagnosed, and 6 (1.4%; 95% CI, 0.5-3.2) developed clinical (...) hepatitis, none of whom had serious symptoms. The only 2 factors independently associated with isoniazid hepatotoxicity were excessive alcohol consumption (odds ratio [OR]; 4.2, 95% CI, 1.6-10.8; P=.002) and a high baseline alanine transaminase level (OR, 4.3; 95% CI, 1.6-11.4; P=.002). The presence of hepatitis C virus antibodies was associated with hepatotoxicity only on univariate analysis. Treatment with isoniazid in drug users appears to be safe and well tolerated, although frequent asymptomatic

2003 Clinical Infectious Diseases

28338. Hepatitis C: magnitude of the problem. (Abstract)

Hepatitis C: magnitude of the problem. 1. End-stage liver disease associated with hepatitis C virus (HCV) infection has become the leading indication for liver transplantation in the United States. 2. Patients with end-stage liver disease caused by HCV may have such associated comorbidities as chronic alcoholism, steatosis, or coinfection with human immunodeficiency virus 1 or other hepatitis viruses. These comorbidities may accelerate disease progression. 3. As chronic hepatitis C progresses (...) to cirrhosis, the risk for the development of hepatocellular carcinoma increases; this poses difficult management problems. 4. As patients who underwent transplantation for end-stage liver disease caused by HCV infection are followed up long term, it has become clear that patient and graft survival are decreased compared with HCV-negative patients or those with cholestatic liver disorders. 5. Risk factors associated with a worse outcome after transplantation include host, viral, donor

2002 Liver Transplantation

28339. Natural history and risk factors for progression of hepatitis C virus disease and development of hepatocellular cancer before liver transplantation. (Abstract)

Natural history and risk factors for progression of hepatitis C virus disease and development of hepatocellular cancer before liver transplantation. 1. Chronic infection with hepatitis C virus (HCV) is the leading cause of cirrhosis and the most common indication for liver transplantation in many countries throughout the world. 2. The most significant factors leading to fibrosis progression in patients with chronic HCV infection include the degree of inflammation present on liver biopsy (...) and ongoing alcohol use. 3. Patients with cirrhosis secondary to chronic HCV infection are at increased risk for developing hepatocellular carcinoma (HCC). 4. Achieving a sustained virological response after treatment with interferon, with or without ribavirin, is associated with a reduced risk for the development of cirrhosis and HCC and prolonged survival.

2003 Liver Transplantation

28340. Fibrogenic impact of high serum glucose in chronic hepatitis C. (Abstract)

features of the metabolic syndrome, including steatosis more frequently, as well as faster fibrosis progression rates. High serum glucose was associated with intermediate and advanced, but not with early, fibrosis stages. A high serum glucose was associated with a higher relative risk for significant fibrosis than overweight.High serum glucose, is an independent co-factor of fibrosis in chronic hepatitis C with a higher pro-fibrogenic impact than overweight. (...) Fibrogenic impact of high serum glucose in chronic hepatitis C. There is considerable variability in the rate of fibrosis progression in patients with chronic hepatitis C, most of which is related to factors so far unknown. We tested the hypothesis that high serum glucose and overweight might contribute to this variability.Seven hundred and ten patients with chronic hepatitis C with a known duration of infection and no hepatitis B virus or human immunodeficiency virus coinfection were studied

2003 Journal of Hepatology

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