Showing papers on "Hepatitis published in 1999"
2,566 citations
TL;DR: Older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis, and this is the subgroup of patients who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
1,558 citations
TL;DR: The findings suggest that NASH plays an under‐recognized role in many patients with cryptogenic cirrhosis, most of whom are older, type 2 diabetic and obese females.
1,065 citations
TL;DR: Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase.
Abstract: Liver transplantation for hepatocellular carcinoma (HCC) in patients with cirrhosis is a radical treatment of the tumor and associated precancerous state. It is potentially curative in a proportion of patients. The outcomes of early studies of liver transplantation in this indication were initially unfavorable. Selection of transplant candidates at an early stage, in the absence of extrahepatic spread, gives better survival than surgical resection and alternative nonsurgical treatments. Transarterial chemoembolization can be used for preoperative control of the disease. Adjuvant chemotherapy may be indicated in the postoperative period for the prevention of recurrence in patients with histologic features of invasiveness in the surgical specimen. Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase. Resection may be indicated if the waiting time is likely to be long.
595 citations
TL;DR: HCV genotype 1b–infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes.
527 citations
TL;DR: While most patients with mild chronic hepatitis have a slowly progressive liver disease, the patients with moderate or severe chronic hepatitis may develop cirrhosis within a few years, the incidence of hepatocellular carcinoma is 2-5% per year.
509 citations
TL;DR: Significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made and effective treatment modalities have been developed for persons with chronic infection.
Abstract: Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs.
465 citations
Journal Article•
TL;DR: It is proposed that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced byIFN-gamma and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.
Abstract: The role played by chemokines in regulating the selective recruitment of lymphocytes to different tissue compartments in disease is poorly characterized. In hepatitis C infection, inflammation confined to portal areas is associated with a less aggressive course, whereas T cell infiltration of the liver parenchyma is associated with progressive liver injury and cirrhosis. We propose a mechanism to explain how lymphocytes are recruited to hepatic lobules during bursts of necroinflammatory activity in chronic hepatitis C infection. We report here that lymphocytes infiltrating hepatitis C-infected liver express high levels of the chemokine receptors CCR5 and CXCR3. However, whereas the CCR5 ligands macrophage inflammatory protein-1α and -1β were largely confined to vessels within portal tracts, the CXCR3 ligands IFN-inducible protein-10 and monokine-induced by IFN-γ were selectively up-regulated on sinusoidal endothelium. In vitro, human hepatic sinusoidal endothelial cells secreted IFN-inducible protein-10 and monokine-induced by IFN-γ in response to stimulation with IFN-γ in combination with either IL-1 or TNF-α. This suggests that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced by IFN-γ and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.
435 citations
TL;DR: In this article, the prognosis and risk factors for morbidity and mortality in liver transplantation for hepatitis C virus (HCV)-related liver disease are determined. But, the results of transplantation are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory.
352 citations
TL;DR: The results suggest that MIP-1alpha-induced migration of CCR5-expressing CD8(+) T cells into the portal areas of the liver plays a significant role in causing liver injury in GVHD; thus, C CR5 and its ligand may be the novel target molecules of therapeutic intervention of hepatic GV HD.
Abstract: We examined the molecular pathogenesis of graft-versus-host disease-associated (GVHD-associated) liver injury in mice, focusing on the role of chemokines. At the second week after cell transfer in the parent-into-F1 model of GVHD, CD8(+) T cells -- especially donor-derived CD8(+) T cells -- infiltrated the liver, causing both portal hepatitis and nonsuppurative destructive cholangitis (NSDC). These migrating cells expressed CCR5. Moreover, macrophage inflammatory protein-1alpha (MIP-1alpha), one of the ligands for CCR5, was selectively expressed on intralobular bile duct epithelial cells, endothelial cells, and infiltrating macrophages and lymphocytes. Administration of anti-CCR5 antibody dramatically reduced the infiltration of CCR5(+)CD8(+) T lymphocytes into the liver, and consequently protected against liver damage in GVHD. The levels of Fas ligand (FasL) mRNA expression in the liver were also decreased by anti-CCR5 antibody treatment. Anti-MIP-1alpha antibody treatment also reduced liver injury. These results suggest that MIP-1alpha-induced migration of CCR5-expressing CD8(+) T cells into the portal areas of the liver plays a significant role in causing liver injury in GVHD; thus, CCR5 and its ligand may be the novel target molecules of therapeutic intervention of hepatic GVHD.
320 citations
TL;DR: Successful treatment of CHC improved HQL as measured by both CHC‐specific and generic measures of functional health and well being, as well as changes in HQL among treatment responders.
TL;DR: This review will consider the factors that contribute to perioperative hepatic dysfunction and prediction of operative risk in patients with liver disease undergoing surgery other than liver transplantation.
TL;DR: Results show a clear association between genotype A and chronic outcome and suggest that HBV genotypes may play a role in the virus–host relationship and possible mechanisms for such a role are discussed.
Abstract: Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P-value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus-host relationship. Possible mechanisms for such a role are discussed.
TL;DR: It is suggested that therapy of PBC should be guided by the degree of biochemical and histological hepatic involvement, and the name “overlap syndrome” should be abandoned for “PBC, hepatitic form.”
TL;DR: The data support the view that an immunologic idiosyncrasy, mediated through HLA class II antigens, plays a role in the pathogenesis of drug-induced immunoallergic hepatitis.
TL;DR: In the general population of Northern Italy, HCV infection is widespread, but only less than 50% of the anti-HCV positive subjects, particularly those infected with genotype 1b, are associated with a more severe liver disease.
Abstract: BACKGROUND—The severity, clinical course, and risk of hepatitis C virus (HCV) related chronic liver disease are still rather poorly defined.
AIMS—To investigate the prevalence, risk factors, and severity of HCV related liver disease in the general population, and investigate whether infection with a specific genotype is associated with an increased risk of cirrhosis or hepatocellular carcinoma.
METHODS—HCV RNA determination by polymerase chain reaction (PCR) and HCV genotyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular carcinoma was established by liver biopsy in all cases. All the data were analysed by univariate and multivariate statistics in all the cohort. To investigate the natural history of HCV infection, anti-HCV positive subjects were followed up every six months for three years with liver function tests and ultrasonograms.
RESULTS—The overall prevalence of HCV RNA positivity was 2.3%. Positivity increased progressively with age, and was higher in women (ratio of men to women = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intravenous drug use, blood transfusions received before 1990, history of previous hepatitis among the cohabiting, and history of animal (mainly dogs) bites were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, sex, and alcohol intake, genotype 1b infection, with or without coinfection with other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of follow up, 57 (35%) of the HCV RNA positive subjects had consistently normal alanine aminotransferase and γ-glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcohol a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year).
CONCLUSIONS—In the general population of Northern Italy, HCV infection is widespread, but only less than 50% of the anti-HCV positive subjects, particularly those infected with genotype 1b, are associated with a more severe liver disease. Alcohol consumption greater that 30 g a day significantly aggravates the natural course of the disease.
Keywords: hepatitis C virus genotypes; Dionysos; liver disease; cirrhosis
TL;DR: Increased generation of iPs by alcohol in healthy volunteers is consistent with the hypothesis that oxidant stress precedes and contributes to the evolution of ALD.
Abstract: To address the hypothesis that elevated blood alcohol increases systemic oxidant stress, we measured urinary excretion of isoprostanes (iPs), free radical-catalyzed products of arachidonic acid Ten healthy volunteers received acute doses of alcohol (Everclear-R) or placebo under randomized, controlled, double-blind conditions Urinary iPF2a-III increased in a time- and dosage-dependent manner after dosing with alcohol, with the peak urinary iPF2a-III excretion correlating with the rise in blood alcohol To determine whether oxidant stress was associated with alcohol-induced liver disease (ALD), we then studied the excretion of iP in individuals with a documented history of alcohol-induced hepatitis or alcohol-induced chronic liver disease (AC) Both urinary iPF2a-III and urinary iPF2a-VI were markedly increased in patients with acute alcoholic hepatitis In general, urinary iPF2a-III was significantly elevated in cirrhotic patients, relative to controls, but excretion was more pronounced when cirrhosis was induced by alcohol than by hepatitis C Excretion of iPF2a-VI, as well as 4-hydroxynonenal and the iPF2a-III metabolite, 2,3-dinor-5, 6-dihydro-iPF2a-III, was also increased in AC Vitamin C, but not aspirin, reduced urinary iPs in AC Thus, vasoactive iPs, which serve as indices of oxidant stress, are elevated in the urine in both acute and chronic ALD Increased generation of iPs by alcohol in healthy volunteers is consistent with the hypothesis that oxidant stress precedes and contributes to the evolution of ALD
TL;DR: Sequence determination and phylogenetic analyses demonstrated that isolates from farm animals were not genetically distinct from those found in humans, suggesting that domesticated farm animals serve as a source of human infection.
Abstract: TT virus is a newly described agent infecting humans. Initially isolated from a patient (initials T.T.) with unexplained hepatitis, the virus has since been found in both normal and diseased individuals. In the present study, we utilized genomic-length sequences from distinct genotypes of TT virus to design PCR-based assays using conserved oligonucleotide primers from three independent regions of the virus genome. Each of the three assays was found to be superior to the PCR-based assays previously published. The most sensitive of the new assays was utilized to demonstrate the prevalence of TT virus to be at least 34·1% in volunteer blood donors, 39·6% in commercial blood donors, 59·6% in non-A–GB hepatitis cases, 81·7% in injectable drug users and 95·9% in haemophiliacs. In an attempt to identify a possible source of human infection, we found TT virus sequences to be present in 19% of chickens, 20% of pigs, 25% of cows and 30% of sheep. Sequence determination and phylogenetic analyses demonstrated that isolates from farm animals were not genetically distinct from those found in humans. This study clearly demonstrates that previously reported PCR assays dramatically underestimate the true prevalence of TT virus within the human population. Due to the high rate of infection in both blood donors and those with non-A–GB hepatitis, these results question the causal role of TT virus in cases of unexplained hepatitis. Further, it is possible that domesticated farm animals serve as a source of human infection.
TL;DR: Findings suggest that hepatocytes are the major sites of DEN virus replication in the liver and that DEN virus induces apoptosis of hepatocytes in vivo.
TL;DR: Stable sexual partners of hemophiliacs or recipients of HCV-contaminated immunoglobulin preparations rarely become infected, but other sexual behaviours or confounding non-sexual transmission routes could play a part.
TL;DR: Exposure to AFM1 can account for a substantial part of the risk of HCC in men with chronic HBV hepatitis and adds importantly to the evidence that HCV and family history of H CC increase the risk.
TL;DR: The near full-length sequences of HEV-US1 and a second US isolate verify the presence of a new HEV strain in North America and provide information as to the degree of variability between variants.
Abstract: The partial sequence of a hepatitis E virus (HEV-US1) isolated from a patient in the United States (US), suffering from acute viral hepatitis with no known risk factors for acquiring HEV, has been reported. These sequences were significantly different from previously characterized HEV isolates, alluding to the existence of a distinct human variant. In this paper, we report the near full-length sequences of HEV-US1 and a second US isolate (HEV-US2). HEV-US2 was identified in a US patient suffering from acute viral hepatitis. These sequences verify the presence of a new HEV strain in North America and provide information as to the degree of variability between variants. The HEV-US nucleotide sequences are 92% identical to each other and only 74% identical to the Burmese and Mexican strains. Amino acid and phylogenetic analyses also demonstrate that the US isolates are genetically distinct, suggesting the presence of three genotypes of HEV. Serum from the second US patient induced hepatitis following inoculation into a cynomolgus macaque. Within 2-4 weeks, HEV-US2 RNA was detectable in both the serum and faecal material coinciding with elevated serum alanine transaminase levels. Infection resolved as antibody titres increased 8 weeks post-inoculation.
TL;DR: The Ishak system is associated with good interobserver reliability if a deviance of one categorical level in each variable of the system is accepted as agreement, compared to the Knodell system it provides more detailed information but is less reliable regarding fibrosis.
Abstract: Background: Assessing the histopathological degree of liver damage is essential to the routine care of patients with chronic hepatitis C virus (HCV) infection. Several scoring systems have been proposed in attempts to standardize the histological assessment. One scoring system has been proposed by Ishak et al, Although widely endorsed, its interobserver reliability has not been evaluated. Methods: 95 liver biopsies from patients with chronic HCV infection were scored by three independent observers. Interface hepatitis, confluent necrosis, focal necrosis, portal inflammation, and fibrosis were assessed. Results. Confluent necrosis, which is more common in acute hepatitis, was not seen in any biopsy. For each of the remaining variables of inflammation (periportal hepatitis, focal necrosis, and portal inflammation) we found agreement in 95-96% for all three observers. Kappa scores ranged from 0.11 to 0.41 and weighted kappa scores from 0.18 to 0.53. For staging we noted 84% agreement, kappa scores of 0.26-0.47 and weighted kappa scores of 0.57-0.69. Conclusion. The Ishak system is associated with good interobserver reliability if a deviance of one categorical level in each variable of the system is accepted as agreement. Compared to the Knodell system it provides more detailed information but is less reliable regarding fibrosis.
TL;DR: The pathophysiology, incidence and predictive factors, clinical manifestations, diagnosis and grading, prevention, and treatment for both types of the disease are discussed.
Abstract: Acute graft-versus-host disease denotes a distinctive syndrome characterized by a triad of dermatitis (rash), hepatitis (jaundice), and gastroenteritis (abdominal pain, diarrhea) developing in the first 100 days after allogeneic hematopoietic cell transplantation. Chronic graft-versus-host disease designates a more diverse syndrome, usually presenting with multiorgan involvement and commonly developing 100 days after hematopoietic cell transplantation. This article discusses the pathophysiology, incidence and predictive factors, clinical manifestations, diagnosis and grading, prevention, and treatment for both types of the disease.
TL;DR: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.
TL;DR: The results suggest that silent HBV has some promoting effect forHCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV‐associated CLD.
Abstract: Frequent coinfection of surface antigen-negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)-associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV-associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight-nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs 28.6%, P < .01). With HCV genotype 1b, the serum RNA level was significantly higher (≥106 copies per milliliter vs ≤105 copies per milliliter) in patients with silent HBV than those without coinfection (P < .01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5 ± 104.8 vs 121.8 ± 78.6 IU/l; mean ± SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4 ± 3.8 vs 8.6 ± 4.5; mean ± SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P < .01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV-associated CLD. J. Med. Virol. 58:201–207, 1999. © 1999 Wiley-Liss, Inc.
TL;DR: Clinicians caring for patients with coinfection with HIV and HBV should be aware of the possibility that a hepatitis B flare may occur in previously asymptomatic carrier patients.
Abstract: Lamivudine is a nucleoside analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Patients coinfected with HIV and HBV may have hepatitis flares when lamivudine therapy is discontinued or when resistance of HBV to lamivudine emerges. This retrospective, descriptive study conducted in three tertiary care medical centers describes patients coinfected with HIV type 1 and HBV who presented with a spectrum of clinical and subclinical hepatitic responses to lamivudine withdrawal or resistance. One patient had fulminant hepatic failure and a second patient had subclinical hepatitis when lamivudine therapy was discontinued and a more efficacious antiretroviral regimen was substituted. Three patients had flares of hepatitis after 13 to 18 months of lamivudine therapy. Lamivudine withdrawal or emergence of lamivudine-resistant mutants in patients coinfected with HIV and HBV may result in severe hepatitis. Clinicians caring for patients with coinfection with HIV and HBV should be aware of the possibility that a hepatitis B flare may occur in previously asymptomatic carrier patients.
TL;DR: Drugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage.
Abstract: Background—The long term outcome of drug related liver disease is unknown. Aims—To study the natural history of histologically proved drug induced hepatotoxicity. Methods—110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978‐1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests. Results—Presentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal antiinflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1‐19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug. Conclusions—Drugs should be considered in the diVerential diagnosis of abnormal liver function and/or histology, as failure to withdraw the oVending drug is associated with a high risk of persistent liver damage. (Gut 1999;44:731‐735)
TL;DR: It is reported here that the widely used D-galactosamine/LPS model does not account for septic shock and inhibitors of the ICE caspase family can prevent or even overcome the ongoing hepatic injury induced by TNF-alpha during sepsis, ischemia-reperfusion, or severe hepatitis.
Abstract: Experimental models of sepsis using endotoxin challenges, including studies with sensitized animals with D-galactosamine, have largely contributed to the basic rationale for innovative clinical trials in human septic shock, which have, to date, failed. The ability of these models to reproduce human disease has been highly discussed. We report here that the widely used D-galactosamine/LPS model does not account for septic shock. Treatment with YVAD-CMK, a potent tetrapeptide inhibitor of caspases of the interleukin (IL)-1beta converting enzyme (ICE) family, protects from LPS-induced liver apoptosis and mortality in D-galactosamine-sensitized mice when administered either before or up to 2 h after the lethal challenge. This curative effect is related to complete inhibition of caspase-3 activity in the liver. However, YVAD-CMK does not affect LPS-induced release of IL-1beta and does not protect from a lethal dose of LPS in unsensitized mice. These experiments demonstrate the difference between these two widely recognized experimental models of sepsis. LPS toxicity in D-galactosamine-treated mice, leading to blocked gene transcription, results from tumor necrosis factor (TNF)-alpha-induced caspase-3-dependent liver injury, not from the systemic inflammatory response. These results provide evidence that inhibitors of the ICE caspase family can prevent or even overcome the ongoing hepatic injury induced by TNF-alpha during sepsis, ischemia-reperfusion, or severe hepatitis.