Tomoya Sano

Background and Aim: The World Health Organization has a goal to eliminate the hepatitis C virus (HCV) by 2030. To achieve this, effective screening for HCV is essential. We evaluated the utility of the ELECSYS® HCV Duo immunoassay (Duo assay) for HCV screening. Materials and Methods: This single-center retrospective study included 184 HCV patients from 2014 to 2017. We measured HCV antibody (Duo/Ab) and HCV core antigen (Duo/cAg) using the Duo assay in HCV RNA-positive samples obtained before DAA therapy. We compared Duo/cAg positivity rates according to host and viral factors. We also performed logistic regression analysis and decision tree analysis to identify independent factors and profiles for Duo/cAg false-negative results, respectively. Results: Duo/Ab positivity rates were 100%, and Duo/cAg positivity rates were 78% in all subjects. Duo/cAg positivity rates were 40.0%, 78.6%, and 92.9% at HCV RNA levels ≤4.9, 5.0–5.9, and ≥6.0 log IU/mL, respectively (p30 U/L, and HCV genotype. In multivariate analysis, the HCV RNA level (Unit −1.0 log IU/mL, OR 5.49, CI 3.12–10.56, p

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer deaths worldwide. The etiology of HCC has now dramatically changed from viral hepatitis to metabolic dysfunction-associated steatotic liver disease (MASLD). The main pathogenesis of MASLD-related HCC is the hepatic lipid accumulation of hepatocytes, which causes chronic inflammation and the subsequent progression of hepatic fibrosis. Chronic hepatic inflammation generates oxidative stress and DNA damage in hepatocytes, which contribute to genomic instability, resulting in the development of HCC. Several metabolic and molecular pathways are also linked to chronic inflammation and HCC in MASLD. In particular, the MAPK and PI3K-Akt-mTOR pathways are upregulated in MASLD, promoting the survival and proliferation of HCC cells. In addition, MASLD has been reported to enhance the development of HCC in patients with chronic viral hepatitis infection. Although there is no approved medication for MASLD besides resmetirom in the USA, there are some preventive strategies for the onset and progression of HCC. Sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class of medications, has been reported to exert anti-tumor effects on HCC by regulating metabolic reprogramming. Moreover, CD34-positive cell transplantation improves hepatic fibrosis by promoting intrahepatic angiogenesis and supplying various growth factors. Furthermore, exercise improves MASLD through an increase in energy consumption as well as changes in chemokines and myokines. In this review, we summarize the recent progress made in the pathogenic mechanisms of MASLD-associated HCC. Furthermore, we introduced new therapeutic strategies for preventing the development of HCC based on the pathogenesis of MASLD.

Aims: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct‐acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction‐associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication.Methods: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α‐fetoprotein (AFP), Fibrosis‐4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication.Results: A total of 86 patients (6.7%) developed HCC during the follow‐up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04–1.11, P = 0.0008), Fibrosis‐4 index (HR 1.17, CI 1.08–1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40–6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis‐4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD.Conclusion: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.

Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk.

Aims: The real‐world efficacy of sofosbuvir/velpatasvir treatment for patients with hepatitis C virus‐related decompensated cirrhosis is unclear. We aimed to identify factors that improve liver functional reserve after treatment.Methods: This was a multicenter retrospective study of 12‐week sofosbuvir/velpatasvir treatment. A total of 48 patients with Child–Pugh (CP) class B or C were enrolled at 11 institutions. We evaluated changes in liver functional reserve at 24 weeks post‐treatment.Results: At baseline, 40 and eight patients were CP class B and C, respectively. The overall rate of sustained virologic response 12 weeks post‐treatment was 95.8% (46/48). Serum albumin, alanine aminotransferase and α‐fetoprotein levels, and the FIB‐4 index were significantly improved post‐treatment (P < 0.05). Among patients who achieved sustained virologic response 12 weeks post‐treatment, those with CP class A increased from 0 to 24 patients (56%) at 24 weeks post‐treatment. In multivariate analysis, body mass index (BMI) ≥25 was an independent factor that inhibited CP class improvement (P < 0.05). In decision tree analysis, after treatment, the initial divergent variable for CP class improvement was hepatic encephalopathy, followed by serum sodium level and BMI.Conclusion: Sofosbuvir/velpatasvir treatment improved the liver functional reserve in patients with hepatitis C virus‐related decompensated cirrhosis at 24 weeks post‐treatment. However, BMI ≥25 inhibited improvement in CP class. Additionally, decision tree analysis revealed that a combination of hepatic encephalopathy, serum sodium levels, and BMI were diversity profiles associated with no improvement in liver functional reserve after the treatment.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a systemic inflammatory disorder characterized by the above-mentioned symptoms. Because of the similarity in phenotypes between TAFRO syndrome and decompensated liver cirrhosis, an accurate diagnosis is often difficult. We herein report a 62-year-old Japanese patient with TAFRO syndrome who was misdiagnosed with intractable ascites associated with liver cirrhosis. Improvement of symptoms after treatment with prednisolone was associated with interleukin-6 rather than C-reactive protein. The pathogenesis of TAFRO syndrome, which has similar clinical manifestations to liver cirrhosis, remains unclear, and our findings may help elucidate the concept of this condition.

Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB.

The aim of the present study was to evaluate the effects of switching to tenofovir alafenamide (TAF) in patients who had received a nucleos(t)ide analog (NA) for the treatment of chronic hepatitis B (CHB). The data from 33 Japanese patients with CHB who received TAF therapy after using NA [adefovir dipivoxil (ADV) and/or tenofovir disoproxil fumarate (TDF)] were retrospectively analyzed. Specifically, the biochemical and virological markers from the start of the TAF treatment to 6 months later were assessed. Comparative evaluation was performed by dividing patients into two groups: Long‑term (n=19) and short‑term administration groups (n=14), with a cutoff administration duration of 10 years. In all 33 patients, the levels of serum hepatitis B surface antigen (HBsAg; 1,126±1,724 to 1,001±1,591 IU/ml; Pµg/g·Cre; P=0.002) significantly decreased from baseline after 6 months. Serum HBsAg, serum ALP and U‑BMG/Cr showed a significant reduction in both groups. In conclusion, switching from ADV or TDF to TAF resulted in a decrease in serum HBsAg and improvement in serum ALP and U‑BMG/Cr after 6 months of treatment in patients regardless of history of treatment with NA.