Efficacy of hepatitis C virus eradication after curative treatment for hepatocellular carcinoma in patients with advanced hepatocellular carcinoma and decreased hepatic functional reserve: A nationwide, multicentre study by the Japanese Red Cross Liver Study Group.

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

Efficacy and safety of glecaprevir/pibrentasvir as retreatment therapy for patients with genotype 2 chronic hepatitis C who failed prior sofosbuvir plus ribavirin regimen.

AIM: Rescue therapy for patients with genotype 2 (GT2) chronic hepatitis C who failed prior sofosbuvir (SOF) plus ribavirin (RBV) awaits establishment. This study aims to investigate the efficacy and safety of the fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB) for patients with GT2 chronic hepatitis C. METHODS: In this nationwide observational study undertaken by the Japanese Red Cross Liver Study Group, 28 GT2 patients with prior failure of SOF + RBV were retreated with GLE/PIB for 12 weeks. We evaluated the rate of sustained virologic response (SVR) and adverse events. RESULTS: After 4 weeks of therapy, serum hepatitis C virus RNA was below the limit of quantification in all patients. The SVR after 4 and 12 weeks of the end of treatment was validated in 100% (28/28) and 100% (28/28), respectively. The adverse events comprised pruritus (eight patients), fatigue (four patients), and appetite loss (four patients), all of which were mild in severity. CONCLUSIONS: This study establishes the efficacy of GLE/PIB as retreatment in Japanese patients with GT2 chronic hepatitis C not responding to SOF + RBV.

Real-world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group.

AIM: This study aimed to describe the real-world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2. METHODS: This was a retrospective analysis of a nationwide, multicenter registry including 914 hepatitis C genotype 2 Japanese patients treated with SOF + RBV for 12 weeks. The rate of sustained virologic response at 12 weeks after treatment (SVR12), incidence of adverse events, and changes in serological parameters were analyzed. RESULTS: Treatment was completed in 98.9% of patients. Ribavirin dose reduction was required in 29.7% of patients. The SVR12 rate was 96.8% in the intention-to-treat population and 97.6% in the per-protocol population. Factors associated with SVR12 were absence of advanced fibrosis (odds ratio, 5.76, P = 0.003) and interferon-treatment-naïve status (odds ratio, 4.79, P = 0.017). Dose reduction or total adherence of RBV was not associated with SVR. The resistance-associated substitution S282 T in NS5B was not detected in any patient at virologic failure. Serum albumin levels significantly increased, and the degree of increase was greater in patients with advanced fibrosis than in those without (0.21 ± 0.32 vs. 0.05 ± 0.29, P < 0.0001). Alpha-fetoprotein decreased significantly at end of treatment (P < 0.0001), and the degree of decrease was greater in patients with advanced fibrosis than in those without (21.7 ± 60.8 vs. 2.5 ± 15.5, P < 0.001). The most commonly reported adverse event was anemia (13.7%). CONCLUSIONS: Treatment with SOF + RBV was highly effective and safe in Japanese patients with HCV genotype 2 infection.

Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group.

AIM: The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS: This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS: Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy. CONCLUSIONS: The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first-line treatment for DAA-naïve patients with HCV.

IL28B gene polymorphism is correlated with changes in low-density lipoprotein cholesterol levels after clearance of hepatitis C virus using direct-acting antiviral treatment.

BACKGROUND: Direct-acting antivirals (DAAs) rapidly clear hepatitis C virus (HCV), but the lipid dynamics after DAA treatment remain unknown. Low-density lipoprotein (LDL) cholesterolemia is the predicting factor for the onset and death of atherosclerotic cardiovascular diseases. Thus, in this study, we examined the frequency and risk of hyper-LDL cholesterolemia in HCV patients who achieved sustained virologic response (SVR) with DAA treatment. METHODS: A total of 121 patients with HCV genotype 1b, who achieved SVR with DAA treatment, were examined for serum levels of total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein, and triglycerides from the start of treatment until 2 years after SVR (SVR-2y). ΔLDL-C was defined as the change in LDL-C levels from treatment initiation to SVR-2y. Hyper-LDL cholesterolemia was defined as ≥ 140 mg/dL LDL-C at SVR-2y. Stepwise multiple regression analysis was performed to determine whether ΔLDL-C and hyper-LDL cholesterolemia are associated with other factors, including viral kinetics. RESULTS: A total of 63, 3, and 55 patients were administered daclatasvir + asunaprevir, ombitasvir + paritaprevir + ritonavir, and ledipasvir + sofosbuvir, respectively. ΔLDL-C in patients with the IL28B (rs8099917) TG/GG genotype was significantly higher than in those with IL28B TT (27.3 ± 27.0 and 9.6 ± 27.3 mg/dL; P < 0.001). In addition, IL28B TG/GG was an independent risk factor for hyper-LDL cholesterolemia (odds ratio: 8.47; P < 0.001). CONCLUSIONS: An IL28B polymorphism is associated with ΔLDL-C and hyper-LDL cholesterolemia after achieving SVR. Thus, lipid markers should be carefully monitored in patients who achieve SVR with DAA.

Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis.

AIM: To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV). METHODS: A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken. RESULTS: The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared. CONCLUSIONS: For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2.

Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2.

Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients.

Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats (P < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats (P < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls (P < 0.05). The level of hepatic liver X receptor (LXR)ß mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a useful detection method for advanced primary biliary cirrhosis.

AIM: In primary biliary cirrhosis (PBC), damaged hepatocytes resulting from chronic cholestasis follow a compensatory mechanism that alters hepatobiliary transporter expression to reduce the accumulation of potentially toxic compounds such as bile acid. Organic anion transporter peptide 1B3 (OATP1B3), which transports agents such as gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), has reduced expression in the late stages of PBC. Therefore, we investigated the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as a useful detection method for the advanced staging of PBC. METHODS: Stage I-III PBC (non-liver cirrhosis [LC]-PBC, n = 12), stage IV (LC-PBC, n = 6), and non-PBC patients (control group, n = 4) were included in this study. We obtained liver tissue samples by percutaneous liver biopsy. Hepatic OATP1B3 expression was determined immunohistochemically, and OATP1B3 mRNA levels were assessed using real-time reverse transcription polymerase chain reaction. The relative enhancement (RE) in the hepatobiliary phase was calculated using the signal intensity of Gd-EOB-DTPA-enhanced MRI. RESULTS: Immunohistochemistry revealed markedly reduced expression of OATP1B3 in hepatocytes around the central vein in LC-PBC patients. Hepatic OATP1B3 mRNA expression in LC-PBC patients was significantly lower than that in non-LC-PBC patients (P < 0.05). The RE on MRI was significantly decreased in the LC-PBC group (0.33 ± 0.14) compared with the non-LC-PBC (0.91 ± 0.15, P < 0.01) and control (0.92 ± 0.20, P < 0.01) groups. CONCLUSION: Gd-EOB-DTPA-enhanced MRI may provide a useful detection method for liver disease in patients with LC-PBC.

[A case of liver abscess due to Streptococcus anginosus infection secondary to a dental extraction].

A 74-year-old man was referred to our hospital because of a high fever. He had undergone a dental extraction about 1 month prior to admission because of apical periodontitis. Imaging study revealed liver abscess lesions. Infection with Streptococcus anginosus was confirmed using both stab and blood culture. An adequate selection of antibiotics was administered, and a good outcome was obtained. There have been no case reports of liver abscess caused by intraoral commensal flora related to dental extraction in healthy adults. This case shows that liver abscesses can occur secondary to dental extractions, even in healthy adults.

Immunohistochemical demonstration of transferrin receptor 1 and 2 in human hepatocellular carcinoma tissue.

BACKGROUND/AIMS: Recent studies have confirmed that iron overload is involved not only in liver carcinogenesis, but in its progression. Results in studies using liver cancer cell lines have suggested a relationship between transferrin receptor (TfR) expression and liver carcinogenesis, but TfR expression has not yet been analyzed in human hepatocellular carcinoma (HCC) tissues. METHODOLOGY: We immunohistochemically assessed the expression of TfR1 and TfR2 in tumor tissues and adjacent non-tumorous liver tissues from 41 HCC patients who underwent partial hepatectomy. We evaluated uptake of iron in hepatocytes and HCC cells using iron staining. RESULTS: The expression TfR was significantly higher in HCC samples than in adjacent non-tumor tissue (p < 0.001). TfR expression was significantly related to serum alpha-fetoprotein (p < 0.05) and des-gamma carboxy prothrombin (p < 0.05) concentrations. We also found iron deposition in non-tumor tissue from 25 patients, but in only two HCC samples, consistent with findings that hepatocellular iron uptake decreases with liver carcinogenesis. CONCLUSIONS: We investigated the expression of TfR1 and TfR2 in human HCC tissues by immunohistochemistry, the first report demonstrating TfR2 expression immunohistochemically in human HCC. These results suggest that TfR is expressed in response to iron deficiency during liver carcinogenesis.

Why is radiofrequency ablation therapy applied for hepatocellular carcinoma up to 3 nodules and smaller than 3 cm in tumor size?

BACKGROUND/AIMS: Radiofrequency ablation (RFA) has been applied for hepatocellular carcinoma (HCC) up to 3 nodules, within 3 cm in size. However, the scientific rationale of the treatment criteria for RFA has not been well analyzed. We compared the number and size of tumors with recurrence rates and survival rates. METHODOLOGY: The study participants retrospectively were enrolled 625 consecutive cases of naïve HCC treated with RFA. We analyzed recurrence rates and survival of 472 for the patients with HCC ≤ 3 nodules, ≤ 3 cm in size (Group A), and 153 for the patients exceeding limits (Group B). RESULTS: Median follow-up was 2.97 years. The survival rate of Group A was significantly higher than that of Group B (5 years: 55.6% vs. 44.2%, 10 years: 27.4% vs. 15.7%; P<0.05). Multivariate analysis of predictors for prognostic factors demonstrated that meeting the RFA criteria, Child-Pugh score A, and lower levels of des-gamma carboxy prothrombin (DCP) were independent factors significantly affecting prognosis. CONCLUSIONS: The present study is the firstto elucidate the scientific rationale for RFA treatment criteria for HCC regarding tumor number and size. We confirmed that the RFA treatment criteria select patients who stand to gain the most from RFA.

Pilot Study of Hepatic Arterial Infusion Chemotherapy with Interferon-beta and 5-fluorouracil: A New Chemotherapy for Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND/AIMS: The present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-ß) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODOLOGY: We studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-ß (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks. RESULTS: Six (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed. CONCLUSIONS: HAIC with IFN-ß and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.

Restoration of albumin production by nucleoside analogue therapy in patients with chronic hepatitis B.

The clinical course of patients with chronic hepatitis B (CH-B) was greatly changed by the introduction of nucleoside analogues. We often encounter patients where the serum level of albumin recovers quickly following the treatment. In this study, we focused carefully on the changes in serum albumin level noted during nucleoside analogue therapy, in an effort to clarify the mechanism behind the restoration of albumin production. We observed changes in serum albumin levels during nucleoside analogue therapy in 12 patients with CH-B and studied the mechanism behind the restoration of albumin production following the therapy. The serum level of albumin was significantly increased very soon after the treatment was started. Prior to treatment with nucleoside analogues, the albumin signal for mRNA was only slightly seen in the peri-portal area, whereas 12 months after the treatment, the liver tissue presented an obvious signal of albumin mRNA. Serum levels of hepatocyte growth factor (HGF) were significantly decreased 12 months after the treatment. In this study, we demonstrated that nucleoside analogues decrease HGF through the suppression of hepatocyte damage, leading to the restoration of albumin production in patients with CH-B.

3-Hydroxyl-3-methylglutaryl-coenzyme A reductase is up regulated in hepatocellular carcinoma associated with paraneoplastic hypercholesterolemia.

Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. However, cholesterol overproduction in HCC tissue has never been demonstrated. An aim of this study is to prove cholesterol overproduction in the HCC tissue of patients with paraneoplastic hypercholesterolemia. Six patients with HCC associated with paraneoplastic hypercholesterolemia and three control patients with HCC who did not have hypercholesterolemia were investigated regarding the expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in HCC tissue by means of immunohistochemical technique. In HCC associated with paraneoplastic hypercholesterolemia, HMG-CoA reductase was clearly stained in cancer cells whereas surrounding non-tumorous hepatocytes showed only slight expression of HMG-CoA reductase. In contrast, HCC tissues derived from patients without paraneoplastic hypercholesterolemia showed only slight expression of HMG-CoA reductase whereas surrounding non-tumorous hepatocytes showed a clear expression of HMG-CoA reductase. We morphologically proved cholesterol overproduction in HCC tissue derived from patients with paraneoplastic hypercholesterolemia. Immunohistochemistry for HMG-CoA reductase thought to be useful in the diagnosis of paraneoplastic hypercholesterolemia.

Limitation of repeated radiofrequency ablation in hepatocellular carcinoma: proposal of a three (times) × 3 (years) index.

BACKGROUND AND AIM: Percutaneous radiofrequency ablation (RFA) has been shown to be a highly effective treatment for hepatocellular carcinoma (HCC). We investigated the controllability of HCC and explored the algorithm of therapeutic strategy for HCC in patients who met the RFA criteria. METHODS: We enrolled 472 patients with HCC who met the RFA criteria (≤ 3 nodules, ≤ 3 cm) and underwent RFA for initial therapy. Patients who underwent repeated RFA were evaluated retrospectively when HCC exceeded the RFA criteria, or the functional hepatic reserve progressed to Child-Pugh grade C. RESULTS: Overall survival rates were: 1 year, 96%; 3 years, 79%; and 5 years, 56%. In 5 years, 14% of patients progressed to Child-Pugh grade C. Meanwhile, 47% of patients exceeded the RFA criteria. Annually, 8% of patients deviated from the RFA criteria. The percentage of patients who were able to receive RFA significantly decreased at the fourth session compared with up to the third session. The survival rates decreased at the rate of 7% annually until the third year after the initial RFA. Afterwards, it shifted to a decrease at the rate of 12% annually. In a multivariate analysis, the presence of hepatitis C virus infection and the existence of a single tumor were identified as significant independent factors contributing to probabilities exceeding the RFA criteria. CONCLUSIONS: HCC was controlled by RFA up to three RFA treatments and 3 years from the initial therapy. On this basis, we propose a "three (times) × 3 (years) index" for considering a shift from RFA to other treatment modalities.

Systemic chemotherapy using carboplatin and 5-fluorouracil for extrahepatic metastasis of hepatocellular carcinoma.

BACKGROUND/AIMS: We have evaluated the effectiveness of systemic chemotherapy for patients with extrahepatic metastasis from hepatocellular carcinoma. METHODOLOGY: We examined the background, survival rates, median survival time and side effects of 15 cases in which systemic chemotherapy using carboplatin and 5-fluorouracil was done (chemotherapy group) and 59 cases in which chemotherapy was not done (non-chemotherapy group) out of a total of 74 cases of patients with extrahepatic metastasis from hepatocellular carcinoma. RESULTS: The prognoses of the 15 chemotherapy cases and the 59 non-chemotherapy cases were as follows: 66.0%, 33.3%, 20.0% at 6 months, 12 months, 18 months respectively for the chemotherapy cases and 44.0%, 18.2%, 7.1% respectively for the non-chemotherapy cases. Median survival periods were 10.7 months for the chemotherapy group and 5.1 months for the non-chemotherapy group. A significantly better prognosis of survival (p=0.037) was identified in the chemotherapy group and no serious side effects were observed. CONCLUSIONS: The present research preceded the approval of sorafenib. This systemic combination chemotherapy will provide an extended survival prognosis and is thus considered to be comparatively safe and effective in those patients.

Male-specific Association between Iron and Lipid Metabolism Changes and Erythroferrone after Hepatitis C Virus Eradication.

Objective Hepatitis C virus (HCV) eradication is associated with decreased serum ferritin and increased serum low-density lipoprotein-cholesterol (LDL-C) levels, although the mechanisms underlying these changes remain unclear. This study aimed to identify the mechanisms underlying the changes in iron and lipid metabolism after HCV eradication. Methods We retrospectively investigated iron and lipid metabolism changes in 22 patients with chronic hepatitis or compensated liver cirrhosis with HCV genotype 1b infection after HCV eradication. We measured the serum erythroferrone (ERFE) levels to assess the association with these metabolic changes. Patients were administered ledipasvir 90 mg and sofosbuvir 400 mg once daily for 12 weeks and were observed for 12 more weeks to evaluate the sustained virological response. Results Half of the patients were men. At baseline, the serum ferritin and ERFE levels were elevated, while the serum LDL-C levels were within the normal range. All patients achieved a sustained virological response at 24 weeks; furthermore, the serum ferritin and ERFE levels were significantly decreased, and the serum LDL-C levels were significantly increased at 24 weeks from baseline (p<0.001, all). In men, a decrease in serum ERFE levels was correlated with changes in the serum ferritin and LDL-C levels (r=0.78, p<0.01; r=-0.76, p<0.01, respectively). In addition, a decrease in the serum ferritin levels was correlated with an increase in the serum LDL-C levels (r=-0.89, p<0.001). These correlations were not observed in women. Conclusion Our results suggest a possible association between iron and lipid metabolism changes and the involvement of ERFE after HCV eradication in men as well as potential sex-related differences.

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BACKGROUND: A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. OBJECTIVE: This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. PATIENTS AND METHODS: This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. RESULTS: After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). CONCLUSIONS: ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.