Interferon therapy for flare-up of hepatitis B virus infection after emergence of lamivudine-induced YMDD motif mutant.

A 61-year-old man with chronic hepatitis B was treated with interferon (IFN)-alpha for flare-up after the emergence of a lamivudine-induced YMDD motif mutant. The YMDD mutant emerged 13 months after the initiation of lamivudine therapy. Despite this, lamivudine therapy was continued.

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C.

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation.

Efficacy of IFN therapy based on duration period of negative HCV-RNA during IFN administration.

We assessed the relationship between the duration period of negative hepatitis C virus (HCV)-RNA during interferon (IFN) therapy and the efficacy after prolonged IFN therapy in patients with HCV-genotype 1b and high virus load of more than 1 mega equivalents/ml (Meq/ml) retrospectively. A total of 100 patients who had HCV-genotype 1b and a high virus load of more than 1 Meq/ml and were treated with natural IFN-alpha for more than 12 months were enrolled in this trial. These patients were given 6 MU of IFN daily for 8 weeks, followed by three times weekly for another more than 44 weeks.

Progressive and sufficient decrease of hepatitis B core antibody can predict the disappearance of hepatitis B virus DNA in Japanese patients with hepatitis B surface antigen clearance.

The aim of this study was to elucidate the relationships among serum levels of hepatitis B virus (HBV) DNA, periods after hepatitis B surface (HBs) antigen clearance, and the titer of hepatitis B core (HBc) antibody in 200-fold diluted serum. Twelve patients who had clearance of HBs antigen from serum were studied. Five patients had not received any treatment (group A), and seven had received prednisolone withdrawal therapy.

Distinction between chronic hepatitis and liver cirrhosis in patients with hepatitis C virus infection. Practical discriminant function using common laboratory data.

In order to distinguish patients with cirrhosis from those with chronic hepatitis, multivariate discriminant analysis was performed using common laboratory data. A total of 205 consecutive patients were diagnosed by peritoneoscopy and biopsy as having chronic liver disease caused by hepatitis C virus (HCV), 168 with chronic hepatitis and 37 with cirrhosis. Twenty variables and their natural logarithmic transformation were employed in the multivariate analysis.

Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are well known predictive factors of poor response to interferon (IFN) therapy. In addition, a sparsity of amino acid substitutions in the interferon sensitivity determining region (ISDR) is also predictive of a poor response to IFN in patients with genotype 1b, although this issue is still controversial. Recently, a 12 amino acid domain in the E2 protein of HCV (PKR-eIF2 alpha phosphorylation homology domain [PePHD]) has been reported to bind with and block the virus replication inhibition ability of PKR, suggesting that the interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of IFN.

Relationship between five-year histological outcome and serial changes in serum alanine aminotransferase in patients with biochemical and virological relapse after interferon treatment for chronic hepatitis C.

Objective: The aim of this study was to assess the correlation between serial changes in serum alanine aminotransferase (ALT) levels and histological outcome 5 years after treatment of patients with chronic hepatitis C with interferon (IFN).

Methods: We retrospectively evaluated 61 consecutive patients who underwent two liver biopsies, just before and 5 years after a 6-month course of IFN therapy, and who showed a relapse after therapy. The extent of liver fibrosis was estimated using a scale with seven grades.

Increased response rate to interferon therapy after a second course in hepatitis C patients who show relapse after the initial course.

Some patients with chronic hepatitis C become HCV-RNA seronegative during interferon (IFN) therapy. However, about one-half of these patients show a relapse, evident by high serum alanine aminotransferase (ALT) level. In some patients with biochemical relapse, the serum HCV-RNA level becomes low immediately after the ALT relapse.

Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer.

Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy, we conducted a prospective randomized controlled trial of interferon (IFN) in patients with chronic liver disease caused by hepatitis C virus (HCV). Twenty eligible patients with cirrhosis were randomized into two groups: 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy. One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy.

Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis.

Background: Hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma. However, the risk factors for primary cholangiocellular carcinoma of the liver (PCC-L) have not been fully investigated. The authors determined the incidence of PCC-L in patients with HCV-related cirrhosis.

Hepatic vascular side effects of styrene maleic acid neocarzinostatin in the treatment of hepatocellular carcinoma.

Styrene-maleic acid neocarzinostatin (SMANCS) sometimes causes hepatic vascular side effects, including arterial stricture, obstruction, and arterio-portal shunt. A total of 128 intra-arterial SMANCS injection treatments, performed for 89 patients with hepatocellular carcinoma, were analyzed to determine the relationship between angiographic findings and subsequent hepatic vascular injuries. After SMANCS therapy, hepatic arterial stricture or obstruction occurred in 5 patients (5/128; 3.

Chronic liver disease in the extremely elderly of 80 years or more: clinical characteristics, prognosis and patient survival analysis.

Background/aims: This study aimed to elucidate the clinical characteristics of patients with chronic liver disease aged 80 years or more, especially the factors affecting prognosis and carcinogenesis.

Methods: A total of 135 patients aged 80 years or above were divided into chronic liver disease without cirrhosis (non-LC) and cirrhosis (LC) groups according to the severity of fibrosis, and the clinical characteristics and prognoses were evaluated.

Results: Seventy-three (54.

Time course of histological changes in patients with a sustained biochemical and virological response to corticosteroid withdrawal therapy for chronic hepatitis B.

Objective: Although biochemical and virological responses to corticosteroid withdrawal therapy for chronic hepatitis B have been extensively studied, long term changes in liver histology have not been well documented.

Methods: We retrospectively analyzed 45 paired liver biopsy specimens taken before and after treatment from 40 patients who persistently showed biochemical remission and an absence of HBe antigen (RIA) for up to 20 yr.

Results: The grading scores for necroinflammatory and fibrotic activity in the liver specimens decreased significantly after corticosteroid withdrawal therapy.

Clinical and virological features of chronic hepatitis C carriers with normal alanine aminotransferase levels despite positive serum HCV-RNA after interferon therapy.

Interferon (IFN) is the only drug that induces viral clearance, but in patients with chronic hepatitis C, HCV-RNA clearance is achieved in only 20%-40% of patients treated with IFN for 6 months. The remaining patients have positive serum HCV-RNA, but about 5%-15% of the patients with positive serum HCV-RNA after IFN therapy showed normal alanine animotransferase (ALT) levels (incomplete response; ICR). In these patients, IFN therapy is thought to be related to the suppression of necroinflammatory reaction in the liver.

Combined ursodeoxycholic acid and glycyrrhizin therapy for chronic hepatitis C virus infection: a randomized controlled trial in 170 patients.

Objective And Design: To assess the efficacy and safety of combination therapy using ursodeoxycholic acid with glycyrrhizin for chronic hepatitis C virus infection, we conducted a prospective randomized controlled trial of glycyrrhizin (group G) compared with glycyrrhizin plus ursodeoxycholic acid (group G+U) in 170 patients.

Methods: All patients had elevated serum aminotransferase levels over 6 months before entry into the trial. Glycyrrhizin was administered to both groups for 24 weeks, and in group G+U, ursodeoxycholic acid (600 mg/day) was administered orally as well.

Enzyme-linked immunosorbent assay to detect hepatitis C virus serological groups 1 to 6.

By conventional serological grouping methods, it is possible to determine hepatitis C virus (HCV) serological groups for genotypes 1a, and 1b, and genotypes 2a, and 2b, but not for other genotypes, i.e., 3a, 3b, 4a, 5a, and 6a.

Fluctuations of hepatitis C virus load are not related to amino acid substitutions in hypervariable region 1 and interferon sensitivity determining region.

Hepatitis C virus (HCV) load is one of the most important predictive factors of response to interferon treatment. However, little is known about the mode and determinants of viremia. The mode of viremia was investigated in 78 patients with chronic HCV genotype 1b infection during 1-2 years follow up.

Efficacy and changes of the nonstructural 5A GENE by prolonged interferon therapy for patients with hepatitis C virus genotype 1b and a high level of serum HCV-RNA.

Object: The aim of this study was to examine the efficacy and the changes of amino acid sequences of the interferon sensitivity-determining region (ISDR) by prolonged interferon (IFN) treatment in patients who have serum hepatitis C virus (HCV)-genotype 1b and a high level of serum HCV-RNA.

Methods: Inclusion criteria were biopsy-proven chronic hepatitis, positive HCV-RNA, and an abnormal serum aminotransferase level. Twenty-five patients received 6 MU of natural IFN-alpha daily for 8 weeks, followed by three times weekly for 40 weeks (1,056 MU).

[Clinical manifestations and histopathologic features of chronic liver disease with serum TT virus (TTV) DNA positive alone as measured by first generation primer sets].

To determine the clinical manifestations and histopathologic features of serum TTV DNA-positive chronic liver disease, we investigated eleven patients who showed serum TTV DNA alone, as detected by the polymerase chain reaction using first generation primer sets (RD primer series). Clinical manifestations were as follows: (1) biochemical abnormalities of the ALT-dominant and gamma-GTP-dominant types; (2) persistently elevated gamma-GTP despite normalization of ALT in gamma-GTP-dominant type patients; (3) association of TTV with pathogenesis of fatty liver or alcoholic liver dysfunction; and (4) response to liver-protective medicines. Histopathologic features were as follows: (1) inflammation-related cell infiltration scattered within the portal area, with distinguishable necroinflammation in the lobular region; (2) pathologic findings on biliary epithelium; (3) high incidence of steato-metamorphosis involvement; and (4) histologic characteristics undistinguishable from "viral" chronic hepatitis in some liver specimens.

Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection.

Background/aims: The aim of this study was to examine the histological changes in liver biopsies induced by 52 weeks of lamivudine therapy in patients with e-antigen positive and e-antigen negative chronic hepatitis B infection.

Methods: Twenty patients were enrolled into this open-label study. All patients had a liver biopsy within the 4 weeks before starting lamivudine therapy.

Prevalence of TT virus before and after blood transfusion in patients with chronic liver disease treated surgically for hepatocellular carcinoma.

Background: To examine the prevalence of TT virus (TTV) before and after blood transfusion, we retrospectively examined serum samples obtained from 55 patients who received blood transfusions before, during and after resection of hepatocellular carcinoma.

Methods: TT virus DNA was extracted from serum samples and detected by nested polymerase chain reaction. Before transfusion, seven (12.

Predictive value of different hepatitis C serological assays in the treatment of chronic hepatitis C with interferon alpha.

In order to predict the complete response rate of natural interferon-alpha (nIFN-alpha) treatment in patients with chronic active hepatitis C, we examined the predictive value (PV) of different hepatitis C serological assays. We performed first generation (ver.1) and second generation (ver.

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.

The activity of interferon (IFN) is not elucidated from the viewpoint of cancer prevention in chronic hepatitis C patients en masse. The hepatocellular carcinogenesis rate was analyzed statistically in 1,643 patients with chronic hepatitis C: 1,191 patients with IFN therapy and 452 without IFN therapy. Hepatocellular carcinogenesis rates in the treated and untreated groups were 2.

Susceptibility of TT virus to interferon therapy.

TT virus (TTV) is a newly identified single-stranded DNA virus. We retrospectively analysed serum samples from sixteen patients, infected with both hepatitis C virus (HCV) and TTV, and who had been treated with interferon. An elevated serum alanine aminotransferase level after interferon was associated with persistence of HCV (abnormal in five of seven patients with persistence of HCV compared with normal in all nine patients who showed eradication of HCV) irrespective of persistence of TTV.