Search

To explore this possibility, it will be important to confirm whether miR-96-5p can inhibit hepatocellular carcinoma cell growth in vivo. Judging from the number of papers on cancer and microRNAs, including hepatocellular carcinoma, is a field in which many researchers are interested, and the study by Matasui et al.6 is timely in this respect. A similar search using the terms "microRNA" and "hepatocellular carcinoma" found 5642 articles published from 2006 to 2021 (Figure 1). [Extracted from the article]

Aim: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co‐infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct‐acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co‐infected with HCV/HIV may have improved. Methods: This study was conducted to provide updated results of our nationwide survey of LT for patients co‐infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co‐infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). Results: All the patients were men with hemophilia, and the median age was 41 (range, 23–61) years. The median CD4 count before LT was 258 (range, 63–751). Most patients had poor liver function before surgery with Child–Pugh grade C and a Model for End‐stage Liver Disease score of 20 (range, 11–48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct‐acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. Conclusion: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co‐infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co‐infected with HIV/HCV for a better outcome. [ABSTRACT FROM AUTHOR]

As of 31 December 2017, a total of 9242 liver transplants have been carried out in 67 institutions in Japan. There were 447 deceased donor transplants (444 from heart‐beating donors and 3 from non‐heart‐beating donors) and 8795 living‐donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased donor transplants and 347 living‐donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. In terms of hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart‐beating donor (444 transplants: 1 year, 89.1%; 3 years, 85.2%; 5 years, 82.9%; 10 years, 75.4%; 15 years, 70.7%) was similar to that from living‐donor (8794 transplants: 1 year, 85.0%; 3 years, 80.9%; 5 years, 78.5%; 10 years, 73.2%; 15 years, 68.5%; 20 years, 65.7%; 25 years, 64.6%). Graft survival was very much the same as patient survival (heart‐beating donor: 1 year, 88.4%; 3 years, 84.5%; 5 years, 82.2%; 10 years, 74.7%; 15 years, 70.1%; living donor: 1 year, 84.3%; 3 years, 79.9%; 5 years, 77.3%; 10 years, 71.4%; 15 years, 66.3%; 20 years, 63.3%; 25 years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors. [ABSTRACT FROM AUTHOR]

Aims: Previously, our group reported that lymphotropic hepatitis C virus (HCV) could induce various kinds of immune dysfunctions. The immune dysfunctions could cause vascular disease by inducing cryoglobulinemia. It has been reported that ischemic heart diseases might be caused by HCV. However, the infectious rate of HCV in patients with ischemic heart disease has not been clarified in northern Japan. Therefore, we tried to determine the rate of HCV infectivity in patients with ischemic heart disease. Methods: The target patients of this study were automatically selected using an electronic medical record system to exclude selection bias. The system identified 16 484 patients with ischemic heart disease who were included in this study. In addition, 12 902 subjects who had received medical checkups were included as the control group. Results: The positive rate of HCV antibody among the patients with ischemic disease in our hospital was 2.58%, which was significantly higher (P < 0.01) than in the medical checkup patients (0.84%). The positive rate of HCV antibody in the patients with ischemic heart disease in each age group was significantly higher than in the corresponding age groups of the medical checkup patients. The rate of chronic kidney disease in HCV antibody‐positive patients treated by percutaneous coronary intervention (PCI) was significantly higher than in HCV antibody‐negative patients treated by PCI (P = 0.02). Conclusions: Hepatitis C virus infection might be associated with the pathogenesis of ischemic heart disease and HCV antibody positivity might be a risk factor for ischemic heart disease in northern Japan. [ABSTRACT FROM AUTHOR]

Aim: Combination therapy with sofosbuvir and ribavirin (SOF/RBV) has been recently available for chronic hepatitis C patients with genotype 2 (CHG2) in Japan. The domestic phase III clinical trial showed a high antiviral effect with a relatively safe adverse event (AE) profile. Our aim was to report an important AE detected during treatment. Methods: A prospective multi‐institutional study of 12‐week combination therapy with SOF/RBV for CHG2 was carried out to evaluate efficacy and safety. Results: The eligible subjects included 142 patients. Out of 50 assessable patients, 16% of the patients were diagnosed with hyperuricemia. The proportions of subjects with grade 1, grade 3, and grade 4 hyperuricemia were 12, 2, and 2%, respectively. Serum uric acid (UA) levels at week 1 of the therapy (W1) were numerically the highest during therapy in patients with hyperuricemia, and the ratio of W1/baseline serum UA levels was significantly higher than that of post‐treatment week 4 or 8/baseline serum UA levels in assessable patients. Serum UA levels at W1 were significantly correlated with body mass index. The difference between serum UA levels at W1 and baseline serum UA levels was significantly correlated with the difference between serum creatinine levels at W1 and baseline serum creatinine levels. Conclusions: Elevated serum UA level was a notable AE associated with SOF/RBV therapy for CHG2. However, because of the small number of subjects, the exact frequency of AEs should be re‐evaluated with larger cohorts. We need to remember that elevated serum UA level might develop during the therapy, especially at W1. [ABSTRACT FROM AUTHOR]

Aim This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy. Methods Overall, 530 Japanese patients who were infected with hepatitis C virus genotype 1 received SOF/LDV therapy for 12 weeks, and resistance-associated variants (RAVs) in the hepatitis C virus non-structural protein (NS)5A and NS5B regions were assessed at baseline and virological relapse by direct sequencing. Results Sustained virological response (SVR) rates did not significantly differ between patients with and without NS5A Y93H/N (94.2% [113/120] vs. 97.7% [345/353]), but the SVR rate was significantly lower in patients with prior DCV/ASV therapy compared to those without (69.2% [18/26] vs. 98.4% [496/504], P < 0.001). Among 26 patients with prior DCV/ASV therapy, the prevalence of NS5A multi-RAVs (≥2) was similar between responders and non-responders (61% [11/18] vs. 75% [5/8]), but all patients without RAVs achieved SVR. Multivariate analysis showed that prior DCV/ASV therapy and history of hepatocellular carcinoma were independently associated with treatment failure (odds ratio, 37.55; 95% confidence interval, 10.78-130.76; P < 0.001 for prior DCV/ASV therapy; odds ratio, 4.42; 95% confidence interval, 1.09-18.04; P = 0.03 for the history of HCC). All SOF/LDV failure patients ( n = 8) with prior DCV/ASV treatment had two or more factors of cirrhosis, IL28B unfavorable genotype, and baseline NS5A multi-RAVs. The multiple NS5A RAVs had increased but NS5B substitutions, C316N/A207T/A218S or L159F, had not changed at the time of relapse. Conclusions Prior DCV/ASV therapy is associated with failure of SOF/LDV therapy due to multiple RAVs. [ABSTRACT FROM AUTHOR]

Quantifying the risk of undetected HIV, hepatitis B virus, or hepatitis C virus infection in Public Health Service increased risk donors. Lamentably, these donor livers are often infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Hepatitis B virus infection among American patients with chronic hepatitis C virus infection: prevalence, racial/ethnic differences, and viral interactions. [Extracted from the article]

Aim: The Food and Drug Administration guidelines emphasize that patient-reported outcome (PRO) instruments used in clinical trials must be developed based on a conceptual model, yet existing PRO instruments currently used in clinical trials of hepatitis C virus (HCV) patients are not based on a predetermined model. The purpose of this study was to identify a comprehensive list of health-related quality of life (HRQoL) themes that may be unique to HCV by reviewing qualitative research articles of HCV patients. The information collected from the review was used to develop a preliminary model of HRQoL in HCV patients. Methods: Ovid Medline, Ovid Embase, Ovid PsycINFO and PubMed were searched for peer-reviewed journals from 1989 to 2012. Set inclusion/exclusion criteria were utilized with a focus on HRQoL among HCV patients. Eligible articles that met quality assessment criteria were analyzed using meta-synthesis to generate categories and themes to propose a conceptual model. Results: Ten articles that met the inclusion/exclusion criteria and the quality assessment criteria were reviewed. Eleven themes were identified: physical symptoms, physical activities, guilt, stigma, emotional distress, psychological behavior, social relationship, social activities, work function, sexual function and cognitive function. These were further grouped into six HRQoL domains: physical, psychological/emotional, social,work, sexual and cognitive functionality. Conclusion: The systematic review and the proposed model represent a useful starting point in the critical appraisal of the conceptual underpinnings of PRO instruments used in HCV patients. [ABSTRACT FROM AUTHOR]

Aim 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. Methods A systematic review identified SMV and TVR RCT in Japanese treatment-naïve patients. Bayesian NMA was performed assuming fixed study effects. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Aim Chronic liver disease ( CLD) is a leading cause of death and is defined based on a specific set of underlying cause-of-death codes on death certificates. This conventional approach to measuring CLD mortality underestimates the true mortality burden because it does not consider certain CLD conditions like viral hepatitis and hepatocellular carcinoma. We measured how much the conventional CLD mortality case definition will underestimate CLD mortality and described the distribution of CLD etiologies in Connecticut. Methods We used 2004 Connecticut death certificates to estimate CLD mortality two ways. One way used the conventional definition and the other used an expanded definition that included more conditions suggestive of CLD. We compared the number of deaths identified using this expanded definition with the number identified using the conventional definition. Medical records were reviewed to confirm CLD deaths. Results Connecticut had 29 314 registered deaths in 2004. Of these, 282 (1.0%) were CLD deaths identified by the conventional CLD definition while 616 (2.1%) were CLD deaths defined by the expanded definition. Medical record review confirmed that most deaths identified by the expanded definition were CLD-related (550/616); this suggested a 15.8 deaths/100 000 population mortality rate. Among deaths for which hepatitis B, hepatitis C and alcoholic liver disease were identified during medical record review, only 8.6%, 45.4% and 36.5%, respectively, had that specific cause-of-death code cited on the death certificate. Conclusion An expanded CLD mortality case definition that incorporates multiple causes of death and additional CLD-related conditions will better estimate CLD mortality. [ABSTRACT FROM AUTHOR]

Aim Recurrent hepatitis C ( RHC) and acute cellular rejection ( AR) remain critical problems following liver transplantation ( LT) in hepatitis C virus ( HCV) positive recipients because of the similar clinical features. Discrimination between these conditions can be problematic, and adjunctive biomarkers would be useful to discriminate these processes. The aim of our study was to investigate the possibility of the intragraft mi R-122 and -155 expression as new biomarkers after LT. Methods A total of 29 HCV positive recipients were enrolled in this study. Intragraft expressions of mi R-122 and -155 were studied between RHC predominant ( n = 17) and AR predominant cases ( n = 12) using quantitative reverse transcription polymerase chain reaction. Furthermore, we investigated the correlations between these expression levels and clinical serum parameters. Results Intragraft mi R-122 expression had a good correlation with serum alkaline phosphatase ( P = 0.02), but it was not correlated with the serum HCV viral load. The expression levels of mi R-122 in the AR group were significantly higher than those in the RHC group ( P = 0.0006) and, inversely, the expression levels of mi R-155 in the AR group were significantly lower than those in the RHC group ( P = 0.01). Conclusion Our study emphasizes a useful pattern of mi R-122 and -155 as ancillary markers to discriminate AR predominant cases from RHC in HCV positive patients after LT. [ABSTRACT FROM AUTHOR]

Aim We tried to characterize the pathological features of patients who developed hepatocellular carcinoma ( HCC) with the negative results of both serous hepatitis B surface antigen and hepatitis C virus antibody (non- B, non- C). Methods In a multicenter study in Kyushu, Japan, we studied the histopathological characteristics of non-cancerous liver tissues in 129 patients (103 men and 26 women) with non- B, non- C HCC. The histological liver damage was evaluated for fibrosis (stage) and inflammation (grade) according to the Ludwig classification of chronic hepatitis. In addition, we examined the hepatitis B virus ( HBV) genome in serum samples and liver tissues of 20 patients with non- B, non- C HCC. Results Positivity of serum hepatitis B core ( HBc) antibody, alcohol abuse, diabetes and non-alcoholic steatohepatitis were present in 61 (47%), 76 (59%), 57 (44%) and eight (6%) patients, respectively. The degree of fibrosis was mild (stage 1.6 ± 1.2). The stage of patients with neither serum HBc antibody nor alcohol abuse was significantly lower than the stage of patients with HBc antibody and no alcohol abuse ( P < 0.05). HBV genome was detected in 15 cancerous tissues (75%) and 16 non-cancerous liver tissues (80%) in 20 patients with non- B, non- C HCC. Only three of the 20 patients were positive for serum HBc antibody. Conclusion Non- B, non- C patients appear to develop HCC at a low stage of fibrosis. Occult hepatitis B virus infection is the major risk factor for HCC of non- B, non- C patients in Kyushu, Japan. [ABSTRACT FROM AUTHOR]

Aim The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin-immunoglobulin ( Ig) M immune complex ( IC) as a potential biomarker of chronic liver diseases. Methods Serum levels of Survivin- IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma ( HCC). Results Survivin- IgM IC was lower in healthy subjects (median, 99.39 AU/m L) than in patients with chronic viral hepatitis (median, 148.03 AU/m L; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P < 0.001). Among patients with cirrhosis, those with hepatitis C virus ( HCV) infection showed the highest level of Survivin- IgM IC (median, 633.71 AU/mL; P < 0.001). The receiver-operator curve analysis revealed that Survivin- IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [ AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin- IgM IC, aspartate aminotransferase ( AST) and AST/alanine aminotransferase ( ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients ( AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin- IgM IC significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022). Conclusion Our results suggest that Survivin- IgM immune complex may be used as a potential biomarker for liver damage, particularly for the identification of the HCV-related cirrhotic population. [ABSTRACT FROM AUTHOR]

Depression is a frequent side-effect of interferon-based treatment of patients with chronic viral hepatitis, that may lead to reduction or discontinuation of treatment. Clinical trials data showed the importance of therapy of psychiatric disorders for a successful antiviral treatment. Emerging evidence suggests that interferon may cause depression affecting serotonin synthesis via increased activity of indoleamine 2,3-dioxygenase. Serotonin reuptake inhibitors significantly improve mood disorders, but the use of these drugs requires caution because some studies reported the emergence of mania in patients treated for depression during antiviral therapy. Therefore, this review will examine and discuss the putative role of serotonin and its metabolism in the development of depression during antiviral therapy, focusing on pharmacological interventions to reduce side-effects. [ABSTRACT FROM AUTHOR]

Aim Treatment of hepatitis C genotype 4 ( HCV- G4) with pegylated interferon ( PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta-analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin ( RBV) compared to standard interferon ( IFN) plus RBV. The outcome of interest is sustained virological response ( SVR). Methods We searched for eligible randomized controlled trials ( RCT) through May 2012. Random effects meta-analysis was used to pool the risk ratio ( RR) of achieving SVR across trials. Results Five RCT enrolling 386 patients were included. The PEG IFN/ RBV group had increased likelihood of achieving SVR ( RR = 1.51, 95% confidence interval [ CI] = 1.08-2.10). SVR was significantly higher in PEG IFN-α-2a compared to the -α-2b group ( P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR ( P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity. Conclusion In treatment-naive patients with HCV- G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV. [ABSTRACT FROM AUTHOR]

Aim: Ribavirin, used to treat chronic hepatitis C, can induce hemolytic anemia, forcing the discontinuance of treatment. To establish a predictive measure to help circumvent this, we evaluated the relationship of hemoglobin (Hb) decline with the discontinuance of treatment during the progression of ribavirin-induced anemia. Methods: One hundred and sixteen patients (71% male) with genotype 1 chronic hepatitis C were treated with pegylated interferon (PegIFN) α-2b and ribavirin. The mean age was 50.6 years and 55% were IFN naïve. A decline of Hb concentration by 2 g/dL at two weeks from the start of the treatment (“2 by 2” standard) was adopted as the predictive factor for the progression of anemia. Results: By applying the “2 by 2” standard, with ΔHb ≥ 2 g/dL (34%, n = 39), treatment was discontinued in 12 cases (31%), three of which (8%) because of severe anemia. ForΔHb < 2 g/dL (64%, n = 76), treatment was discontinued in 11 (14%) cases; none due to severe anemia. Ten percent (4/39) of patients showed the minimum Hb ≤ 8.5 g/dL in the ΔHb ≥ 2 g/dL group, with none in the ΔHb < 2 g/dL group ( P = 0.001). Furthermore, the patients with minimum Hb ≤ 8.5 g/dL were found only in the “2 by 2” standard-positive and low CL/F (<15) group (4/29, 14%). Conclusion: Monitoring the Hb decline using the “2 by 2” standard can identify patients who are prone to developing severe anemia. Further prospective studies are needed using ribavirin reduction based on the “2 by 2” standard. [ABSTRACT FROM AUTHOR]

Recurrence of hepatocellular carcinoma (HCC) is frequently observed in patients with hepatitis C virus (HCV) infection and the incidence of HCC recurrence is as high as 20% in these patients even after a complete curative treatment is given for the HCC nodules. We report a 57-year-old female who was referred to our hospital for the treatment of a HCC nodule of 1.8 cm diameter in S5 and having liver cirrhosis of Child–Pugh A classification with HCV infection in April 1999. The HCC nodule showed hypervascularity by computed tomography during hepatic arteriography (CTHA) and was coagulated by microwave under peritoneoscopy. Complete necrosis was confirmed by enhanced-CT scan after microwave coagulation. Thereafter, interferon alfa-2b (3MU, twice weekly) was given but HCV RNA continued to be positive. Thereafter, recurrence of HCC was noted five times in S1, S2, S6; treatment by radiofrequency ablation was given four times; and transarterial chemoembolization was carried out once. Since January 2004, peg-interferon alfa-2a (90 µm/week) has been administered, and no recurrence has been detected until August 2005. She is currently 63 years old, and quite well. Five-year-survival rate in HCC patients treated by radiofrequency ablation is 62.7% in our hospital, however, the recurrence rate is as high as 26.4% per year in the patients with chronic HCV infection. It is a point of controversy when liver transplantation should be recommended in HCC patients with liver cirrhosis of Child-Pugh A classification having chronic HCV infection because of the high incidence of recurrence. [ABSTRACT FROM AUTHOR]