Hepatitis C Virus In Japan Research Articles

Incidence of sexually transmitted hepatitis C virus infection among men who have sex with men in Japan from 2009 to 2023.

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct-acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty-two cases were newly confirmed to be HCV infection in 2009-2019 and a total of 9 cases in 2020-2023, with an incidence rate of 5.04 per 1000 person-years in 2009-2019 and 5.55 per 1000 person-years in 2020-2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non-HIV-infected persons, may be much higher.

Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016

BackgroundDirect-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug–drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population.MethodsThis was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged ≥18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period.ResultsWe analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period.ConclusionsPatients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug–drug interactions.

Naturally occurring, resistance-associated hepatitis C virus NS5A variants are linked to interleukin-28B genotype and are sensitive to interferon-based therapy.

The presence of resistance-associated variants (RAV) may attenuate the efficacy of direct-acting antivirals (DAA) in combination therapy for hepatitis C. The aim of this study was to characterize the NS3 and NS5A regions of hepatitis C virus (HCV) in naturally occurring RAV. The NS3 and NS5A regions of HCV were amplified by nested polymerase chain reaction and their nucleotide sequences were determined by direct sequencing in 493 genotype 1b patients naive to DAA-based therapies. The effect of baseline RAV on response to pegylated interferon and ribavirin therapy was analyzed in 65 patients after stratification by interleukin (IL)-28B genotype. The incidence of RAV was 7.9% in NS3 (V36I/L, 1.2%; T54S, 2.8%; Q80K/R, 3.0%; A156S, 0.2%; and D168E/T, 2.4%) and 20.2% in NS5A (L31I/M, 2.2%; and Y93H, 19.0%). The incidence in interferon experienced and naive patients was similar. The incidence of Y93H in NS5A was significantly higher in the IL-28B TT genotype (rs8099917) than non-TT (27.1% vs 9.5%, P < 0.001). The virological response to pegylated interferon plus ribavirin therapy was not affected by the presence of RAV in IL-28B TT genotype. RAV, especially Y93H in the NS5A region, were highly prevalent in DAA naive patients with genotype 1b HCV in Japan and were linked to IL-28B TT genotype. Interferon-based therapy could be an alternative for patients with RAV because these variants did not attenuate the response to that therapy. The analysis of RAV may impact the selection of the optimal treatment strategy.

Relative efficacy and safety of simeprevir and telaprevir in treatment-naïve hepatitis C-infected patients in a Japanese population: A Bayesian network meta-analysis.

Simeprevir (SMV) is an oral, once-daily protease inhibitor for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. In phase II/III randomized controlled trials (RCT) conducted in Japan, SMV, in combination with peginterferon-α and ribavirin (PEG IFN/RBV), demonstrated potent efficacy in HCV genotype 1-infected patients relative to PEG IFN/RBV and was generally well tolerated. Telaprevir (TVR) in combination with PEG IFN/RBV is licensed for the treatment of HCV in Japan. In the absence of head-to-head comparisons of TVR and SMV in a Japanese population, we undertook a network meta-analysis (NMA) to examine the relative efficacy and safety of SMV and TVR in combination with PEG IFN/RBV. A systematic review identified SMV and TVR RCT in Japanese treatment-naïve patients. Bayesian NMA was performed assuming fixed study effects. Three studies met our inclusion criteria: two SMV and one TVR. SMV showed a higher mean odds ratio (OR) of achieving SVR versus TVR (OR, 1.68 (95% credible interval 0.66-4.26)). SMV showed a lower mean OR of discontinuation: overall, 0.35 (0.12-1.00); and due to AE, 0.87 (0.23-3.34) versus TVR. SMV showed a lower mean OR of experiencing anemia 0.20 (0.07-0.56) and rash 0.41 (0.17-0.99) but a higher mean OR of experiencing pruritus 1.26 (0.46-3.47) versus TVR. In this indirect treatment comparison, SMV, in combination with PEG IFN/RBV, showed a favorable risk-benefit profile compared with TVR with PEG IFN/RBV in Japanese treatment-naïve HCV patients.

The Safety of Chemotherapy for Breast Cancer Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, and more than 880,000 people are estimated to be infected with HCV in Japan. Little information is available on the outcomes of HCV during chemotherapy for solid tumors, and the impact of HCV infection on toxicity of chemotherapy is unknown.Materials and methods: We performed a retrospective survey of 1,110 patients diagnosed with breast cancer between January 2006 and March 2011 at our institution. All patients had been screened for hepatitis C serology at diagnosis of breast cancer. We retrospectively investigated the change in HCV load and the toxicities of chemotherapy, based on review of their medical records.Results: 23 patients were identified as having a positive test for anti-HCV antibodies. Ten of these patients received chemotherapy. Their median age was 66 years. No patient had decompensated liver disease at baseline. Eight patients received cytotoxic agents with or without trastuzumab, and two patients received trastuzumab alone. Four of eight patients who received cytotoxic chemotherapy developed febrile neutropenia and one developed transaminases elevation. Serum HCV-ribonucleic acid (RNA) level before and after chemotherapy was evaluated in six patients. Median serum HCV-RNA level at baseline and after chemotherapy was 6.5 and 6.7 logIU/ml, respectively.Conclusion: Chemotherapy for breast cancer patients with HCV infection is feasible, and viral load doesn't change during the chemotherapy.

Inter‐genotypic recombinant hepatitis C virus strains in Japan noted by discrepancies between immunoassay and sequencing

Genetic recombination plays a significant role in the survival and evolution of hepatitis C virus (HCV), but methodological limitations have hindered the exploration of genetic recombination. HCV serotypes were evaluated in 104 patients with chronic hepatitis C when they initially presented in hospitals. Subsequently, HCV genotypes were analyzed using primers for core gene and NS5B gene. Near-complete nucleotide sequences of eight HCV isolates from two suspected patients with 2b/1b recombinant HCV were analyzed by amplification of nine overlapping regions of HCV-specific oligonucleotide primers at different time points: (i) at the first admission; (ii) before and (iii) after interferon therapy; and (iv) after development of hepatocellular carcinoma. The nucleotide sequence of eight HCV isolates obtained was 9,321-9,471 nucleotides in length, comprising a single ORF (polyprotein of 3,014 amino acids.) and segregated into discordant genotypes of 2b and 1b HCV with a recombination junction in NS2. This study highlights the need for more precise characterization of HCV in clinical samples where there is a discrepancy between immunoassays and sequencing. It also demonstrates the circulation of novel inter-genotypic recombinant HCV in Japan, because the cross over point of 2b/1b recombinant HCV in eight clinical isolates of these two patients differed from previously reported HCV recombinant from the Philippines and Japan.

Identification and characterization of a natural inter-genotypic (2b/1b) recombinant hepatitis C virus in Japan

A hepatitis C virus (HCV) strain (HC10-0804) recovered from a 12-year-old Japanese female with chronic hepatitis C segregated into discordant genotypes, 2b and 1b, in the 5'UTR/core and NS5B regions, respectively, thus suggesting an inter-genotypic recombination. The HC10-0804 isolate had a genomic length of 9,423 nucleotides (nt), excluding the poly(U) tract at the 3' terminus, and encoded a single open reading frame (ORF) for a polyprotein of 3,014 amino acids (aa). Based on Simplot and Bootscan analyses, the crossover point from 2b to 1b was estimated at nt 3443/3444 (aa 1034/1035), just after the beginning of the NS3 region. Comparison of the entire genomic sequence showed that the HC10-0804 strain was only 90.2% identical to the previously reported 2b/1b recombinant strain (SE-03-07-1689) from the Philippines, whose putative crossover point was 24 nt downstream of that of HC10-0804. These results indicate the circulation of a novel inter-genotypic (2b/1b) recombinant HCV in Japan.

Prevalence of coinfection with human immunodeficiency virus and hepatitis C virus in Japan

People with human immunodeficiency virus (HIV) infection are frequently infected with hepatitis C virus (HCV), because of the common transmission routes. Since the dissemination of hyperactive antiretrovirus therapy (HAART), the morbidity and mortality associated with HIV infection have declined. However, the reduction in mortality due to opportunistic infection has made HCV-associated liver diseases the leading cause of mortality in Western countries. A similar situation is assumed in Japan, but the status of coinfection with HIV and HCV is unclear. We conducted a nationwide survey to determine the prevalence of coinfection with HIV and HCV by distributing a questionnaire to the hospitals in the HIV/AIDS Network of Japan. Among 4877 patients reported to be HIV-positive, 935 (19.2%) were also positive for the anti-HCV antibody. Most (84.1%) of the patients coinfected with HIV and HCV were recipients of blood products. These data, for the first time, show the current status of coinfection with HIV and HCV in Japan. A detailed analysis of the progression and severity of liver diseases in the coinfected patients is expected.

Lack of Epidemiological Evidence for a Role of Resolved Hepatitis B Virus Infection in Hepatocarcinogenesis in Patients Infected with Hepatitis C Virus in Japan

Objective: The role of resolved hepatitis B virus (HBV) infection in promoting hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) in Japan was evaluated by epidemiological surveys. Methods: Antibody to hepatitis B core (anti-HBc) was determined in age-matched blood donors, and the frequency was compared with that in patients with HCV-associated HCC in Japan. Results: Anti-HBc was detected significantly more frequently in the blood donors with than without antibody to HCV (anti-HCV; 76/135 or 56.3% vs. 65/255 or 25.5%, p < 0.001). In the patients with HCV-associated HCC, anti-HBc was detected in 109 of 202 (54.0%), which was comparable to the frequency in anti-HCV-positive blood donors (56.3%). Among the blood donors with anti-HCV, the prevalence of anti-HBc was no different between those with and without HCV RNA in serum (40/77 or 51.9% vs. 36/58 or 62.1%). Conclusions: The individuals of an age with high cancer frequency (≧40 years) in Japan would have been exposed to HBV frequently (>50%), whether or not they have developed HCV-associated HCC. Despite repeated assertions in the literature, no epidemiological evidence was obtained for a role of past HBV infection in hepatocarcinogenesis in patients infected with HCV in Japan.

Detection of hepatitis B virus X-region DNA in liver tissue from patients with hepatitis C virus-associated cirrhosis who subsequently developed hepatocellular carcinoma.

The risk of hepatocellular carcinoma (HCC) in patients chronically infected by hepatitis C virus (HCV) is relatively higher in Japan than in Western countries. The presence of hepatitis B virus X (HBX)-DNA in the liver tissue samples obtained on enrollment from 69 patients with HCV-associated cirrhosis who were subsequently followed in our hospital was analyzed by polymerase chain reaction (PCR). During the follow-up period of 5.7+/-3.2 years (mean +/- SD), 52 (75%) of 69 patients developed HCC. The PCR analysis indicated that the HBX-DNA sequence was detected in 25 (48%) of 52 patients who developed HCC during follow-up, but in only 3 (18%) of 17 patients who did not (P<0.05). These results suggest that HBX, a hepatitis B viral product relevant to hepatocarcinogenesis, is involved in development of HCC in some patients chronically infected by HCV in Japan.

With high dose natural interferon α treatment, prediction of the therapy for patients with chronic hepatitis C: In 215 cases, the multivariate analysis of characteristics between patients and hepatitis C virus

[Background and Aims] The role of hepatitis C virus (HCV) for prediction of the effect of interferon (IFN) therapy is known to many investigations. However, there is available reports on complete response with IFN therapy for predictive factors between characteristics of patients and HCV. Recently, high dose IFN treatment is known to more effective to elevate the eradication rate of HCV in Japan. The alms of the present study is to elucidate the effect of high dose natural IFN-ct (human lymphoblastoid IFN-ct: derived BALL-l) treatment and to analyze predictive factors with the multivariate cox proportional hazard model. [Methods] 215 patients with chronic hepatitis C (153 males and 62 female, mean age 49.9 years) were treated with only 10MU of high dose natural IFNct (OIF-Otsuka Pharma. Co. Ltd.) by intramuscular injection daily for 2 or 4 weeks, followed by three times a week for 20 or 22 weeks; all patients completely agreed to take part in this study. A complete responder was defined as HCV-RNA negative by the end of treatment (24weeks). At an aspect of virus, predictive factors of virus load and genotype were determined by PCR. At an aspect of patient's background, ALT, AST and Platelets were measured by serum samples. All parameters were tested by the multivariate cox proportional hazard model. Data analysis was performed with the computer program SAS jump. [Results] One hundred and twenty five of 215 with genotypelb patients, 51 with genotype2a, and 28 genotype2b patients were included. 140 of 215 patients had more than 106 copies/ml. 48 in 140 patients were responded well, totally 89 in 215 (41.4%). There was no serious adverse effect in all the treated patients. Results of the multivariate cox proportional hazard model are shown in the table below.

Hepatitis C virus and liver diseases

Hepatitis C virus (HCV) was identified molecularly and a procedure for its diagnosis was developed. In Japan, 70-80% of all cases of chronic liver disease, including hepatocellular carcinoma, are associated with HCV infection. Hepatitis C virus is a typical RNA virus with a high mutation rate. At least six variants of HCV have been identified by their nucleotide sequences. These variants are still classified into three types each containing at least two subtypes; that is, 1a (type I) and 1b (type II), 2a (type III) and 2b (type IV), and 3a (type V) and 3b (type VI). Type 1b (type II) is the predominant HCV in Japan. Even HCV cDNA clones isolated from a single patient showed mutations of HCV, especially in envelope-coding regions. Thus HCV may change during the course of chronic hepatitis due to the high mutation rate of HCV itself and elimination of some clones by immune reactions or interferon therapy. These findings explain the higher rate of chronic HCV infection and indicate that production of an effective vaccine is difficult.

Molecular cloning of cDNA of hepatitis C virus (HCV) genome from a healthy carrier in an aboriginal community in Taiwan with high prevalence of HCV infection.

We analyzed hepatitis C virus (HCV) obtained from a healthy HCV carrier in an aboriginal community with high prevalence of HCV infection. By use of random primers and specific oligonucleotide primers, a cDNA fragment of putative non-structural 3 (NS3) region of the HCV genome was cloned by reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from a serum sample of a healthy HCV carrier in Taur-Yuan village. The nucleotide and deduced amino acid sequences from the 583 nucleotides long cDNA were compared with those of equivalent region of HCV of other previously reported clones: [J1, HCV-J (regarded as major type of HCV in Japan) and US prototype]. They had 93.7% (546/583), 93.1% (543/583) and 80.4% (469/583) homology at the nucleotide level and 96.9% (188/194), 96.9% (188/194) and 91.8% (178/194) homology at the amino acid level, respectively. These results showed that HCV prevalent in an aboriginal community in Taiwan is more similar to Japanese type than to the US prototype.