Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 85% of persons with acute hepatitis C develop chronic hepatitis as determined by persistently abnormal serum enzymes and/or viremia (hepatitis C virus [HCV] RNA). Both the acute and chronic illnesses are predominantly asymptomatic. For this reason and because the chronic illness runs an extremely protracted course, it has been difficult to accurately define the frequency and rate of progression to symptomatic or end-stage liver disease, specifically cirrhosis and hepatocellular carcinoma (HCC). Three evaluation strategies have been used. The first, prospective studies beginning from disease onset, have identified over 8 to 14 year follow-up periods that morbidity (symptoms, cirrhosis) and mortality (hepatic failure, HCC) are modest in frequency. The second, prospective studies of subjects with already established chronic liver disease, have demonstrated high rates of development of cirrhosis, HCC, and mortality over relatively short follow-up periods. The third, retrospective/prospective (nonconcurrent prospective) studies, has consisted of follow-up of recipients of HCV-contaminated immunoglobulin and of transfusion recipients from five enzyme-monitored transfusion studies of the early 1970s. The former study identified no mortality, trivial morbidity, and minimal cirrhosis 17 years after infection. The latter, involving hepatitis cases and matched nonhepatitis controls studied over a 20-year period, demonstrated no increase in all-cause but a slight increase in liver-related mortality. Clinically evident chronic liver disease was noted to be minimal among those in follow-up with biochemically defined chronic hepatitis whose biopsy specimens showed no cirrhosis, but common among those with histologically detected cirrhosis. More than 90% of subjects with an original diagnosis of transfusion-related hepatitis C have remained positive for antibody to HCV (anti-HCV), most with persistent viremia. Two thirds of the anti-HCV-positive individuals have biochemically defined chronic hepatitis, whereas one third have persistently normal enzymes. Taken together, available data suggest that in the first two decades after infection, mortality and morbidity are modest in frequency. Both can be expected to increase as the disease advances to the third and fourth decades after acute infection, especially among those with established cirrhosis. The outcome among those with chronic hepatitis but without cirrhosis remains to be determined.
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PMID:Natural history of hepatitis C. 930 59

Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.
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PMID:Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis C. 931 Sep 31

The aim of this study was to evaluate, in patients with chronic hepatitis C, 1) the prevalence and the epidemiological characteristics of GB virus C (GBV-C) infection, 2) the influence of GBV-C on hepatitis C virus (HCV) infection, 3) the pathogenicity of GBV-C in the absence of treatment and under interferon therapy, and 4) the effect of interferon alfa on GBV-C and HCV replications. One hundred fifteen patients with chronic hepatitis C were studied. Before treatment, they were tested for GBV-C RNA by PCR and GBV-C genotype was determined for positive samples. Pretreatment information was collected, including age, gender, source of HCV, estimated duration of HCV infection, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score on liver biopsy, HCV genotype, HCV viral burden and anti-HCV core IgM antibodies. The genetic complexity of the hypervariable region 1 (HVR1) of HCV was studied by PCR-Single Strand Conformation Polymorphism. All patients were treated with 3 to 9 mega units of interferon alfa-2a three times per week for 3 to 6 months. The influence of GBV-C on the evolution of ALT and HCV replication during and after treatment was studied, and GBV-C and HCV RNA were monitored monthly by PCR during this period. Eighteen patients (16%) were GBV-C RNA-positive. Among 11 samples studied, GBV-C genotype 2a was present in 9 cases, 2b in one case and type 3 in one case. GBV-C RNA-positive patients were significantly younger than GBV-C RNA-negative ones (38.4 +/- 11.5 vs. 47.4 +/- 14.0, P = 0.012), a result independent of the route of transmission and the disease duration. No difference between GBV-C RNA-positive and -negative patients was found for other epidemiological parameters (e.g. gender, risk factor for parenteral viral infections, disease duration and HCV genotypes), or for the characteristics of HCV infection and related liver disease (e.g. HCV RNA level, genetic complexity of the HVR1, anti-HCV core IgM, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score). GBV-C did not influence the rates of ALT normalization at months 3, 6 and 12 and of sustained hepatitis C virological response at month 12 of treatment follow-up. During treatment, GBV-C viremia became undetectable in 12 patients (67%) but relapse occurred after treatment withdrawal in all the nine patients with sufficient follow-up. In the remaining six patients (33%), GBV-C resisted interferon. Whatever the effect of interferon on GBV-C replication, the ALT levels correlated with the presence of HCV RNA. In conclusion, GBV-C infection is frequent in patients with chronic hepatitis C, who are mainly, but not exclusively, infected by GBV-C genotype 2a. GBV-C positive patients are significantly younger than GBV-C negative ones. GBV-C does not seem to affect HCV replication, liver disease and responses of HCV infection and liver disease to interferon therapy. GBV-C is sensitive to 3 mega units of interferon alfa administered three times per week in two-thirds of the patients, but relapse is constant with this dosage after treatment withdrawal.
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PMID:GB virus C (GBV-C) infection in patients with chronic hepatitis C. Influence on liver disease and on hepatitis virus behaviour: effect of interferon alfa therapy. 944 6

The article consists in a brief review of pre-treatment evaluation and antiviral treatment of chronic hepatitis C (HCV) infection. Patients with viraemia (i.e. HCV RNA seropositive with the PCR technique) should be evaluated historically if they lack contraindications for interferon alpha (IFN-alpha) treatment. Patients with depression, autoimmune and thyroid disorders, decompensated cirrhosis, or solid organ transplants, are ineligible for-IFN-alpha treatment. If the histological evaluation shows moderate to severe chronic hepatitis, and the HCV RNA level is < 3 million Eq/mL serum as measured by bDNA, naive (i.e. formerly untreated) patients should be given an initial 12-week course of IFN-alpha to evaluate treatment response. Those who become HCV-negative should continue the treatment for 48 weeks to increase the likelihood of sustained virological response after treatment cessation. Treatment should be discontinued in the case of patients still HCV-positive at 12 weeks, as the chances of obtaining sustained response are remote. Patients with higher pre-treatment HCV RNA levels (> or = 3 million Eq/mL) and patients manifesting unsustained response to earlier IFN treatment should receive combination treatment with ribavirin and IFN-alpha, as treatment with IFN alone is associated with poor chances of sustained response. This treatment approach is associated with an estimated sustained response rate in naive patients of 40-50 per cent.
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PMID:[Treatment response in chronic hepatitis C. Content of virus in serum is decisive for the outcome]. 945 44

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5'-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive.
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PMID:GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors. 949 62

Infection with hepatitis C virus (HCV) is usually diagnosed by the presence of antibodies against fusion proteins or peptides derived from different regions of the HCV genome. However, a subgroup of patients with HCV viraemia are seronegative for antibody against hepatitis C virus (anti-HCV) by conventional antibody assays. We analysed serum samples from a patient with liver cirrhosis who tested negative for anti-HCV by a second-generation assay, but positive for HCV-RNA by reverse transcription polymerase chain reaction (RT-PCR) and branched DNA signal amplification. To identify possible mutations that could explain the failure of detection of anti-HCV by second-generation assay, PCR-amplified DNA fragments of the core region derived from the serum were cloned and sequenced. Nucleotide (nt) and amino acid (aa) sequence analyses (nt 1-486, aa 1-162) showed no mutations revealing stop codons, frame-shifts, deletions or insertions, but the presence of two amino acid substitutions (aa 75 and 91) when compared with HCV-J, a prototype strain of genotype 1b isolated from a Japanese patient. One of these two mutations (aa 75) was situated in the second hydrophilic domain of the core peptide, but analysis of the hydropathy profile showed only a little change. The two mutations were identical to those identified in other Japanese HCV isolates. The serum immunoglobulin level and T and B cell counts were normal in our patient. Our data suggest that the absence of anti-HCV in this patient was not due to mutations of major epitopes of HCV. Low-dose prednisolone administration just after transfusion may have induced immunological tolerance against HCV in this patient.
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PMID:Case report: Clinical and virological analyses of a patient positive for hepatitis C virus-RNA by branched DNA assay but negative for anti-hepatitis C virus antibodies. 950 99

Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replicating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine before transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period developed allograft reinfection 240 and 409 days post-transplant. The strain of the reinfecting virus was analyzed, and a mutation in the YMDD region of the viral polymerase conferring resistance to lamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinfection. A transjugular liver biopsy performed 18 months after the emergence of the lamivudine-resistant strain revealed cirrhosis and lobular hepatitis without rejection. The gradient between hepatic vein wedged and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the lamivudine-resistant strain, is without clinical evidence of portal hypertension, although liver enzymes remain elevated. Both patients were given a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progression to cirrhosis. Famciclovir did not appear to be an effective rescue agent in these two patients.
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PMID:Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up. 955 7

The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the natural history of chronic hepatitis B virus (HBV)-infected patients was low. Previous studies regarding the prognosis in such patients were controversial. Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%; all were male subjects) developed serious complications, including 11 with hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with cirrhosis, and 1 with subfulminant liver failure. The overall cumulative probability of complications was 29.8% at 4 years, and it was higher in males (P = .044) and patients aged 45 years or more (P = .006); the latter carried an 8.6-fold increased risk (95% CI: 1.2-64.6; P = .037) of adverse events. Histories of acute or chronic infection by hepatitis A virus, C virus (HCV), or D virus (HDV) were present in 42% of patients. Patients seropositive for antibodies against HCV (anti-HCV) or HDV (anti-HDV) had higher alanine transaminase (ALT) levels (>40 U/L; P = .008) after sero-clearance. HBV DNA was detectable in 31% of 51 subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV or anti-HDV, and also in an HCC patient's serum and tumor. Staining of liver HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results demonstrated that hepatitis B viremia may persist, and adverse complications were not rare in HBsAg-clearance patients. All such patients should be closely monitored, which may allow for earlier detection of HCC.
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PMID:Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis. 993 38

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.
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PMID:Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. 966 63

Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (< 10 x 10(5), 10-100 x 10(5), or > 100 x 10(5) Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived > or = 3 months were reviewed. Mean follow-up was 669 +/- 228 days for IFN patients and 594 +/- 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P = .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P = .04, Cox proportional hazards model); HCV RNA level > 100 x 10(5) Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P = .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P = .05 at 1 month and P = .003 at 3 months) but not in untreated patients (P = .28 at 1 month and P = .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P = .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P < .02). One- and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P = NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.
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PMID:The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation. 973 80


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