ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis.

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

Impact of pemafibrate in patients with metabolic dysfunction-associated steatotic liver disease complicated by dyslipidemia: A single-arm prospective study.

Background and Aim: This study aimed to clarify the efficacy and safety of 48-week pemafibrate treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated by dyslipidemia. Methods: A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks. Results: The participants were 54 males and 37 females, with a median age of 63 (52-71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, and alkaline phosphatase (P < 0.001 for all). A significant decrease in the homeostasis model assessment-insulin resistance (HOMA-IR) was observed in patients with insulin resistance (HOMA-IR ≥ 2.5) (4.34 at baseline to 3.89 at Week 48, P < 0.05). Moreover, changes in ALT were weakly correlated with those in HOMA-IR (r = 0.34; p < 0.05). Regarding noninvasive liver fibrosis tests, platelets, Wisteria floribunda agglutinin-positive Mac-2-binding protein, type IV collagen 7s, and the non-alcoholic fatty liver disease fibrosis score significantly decreased from baseline to Week 48. Most adverse events were Grades 1-2, and no drug-related Grade 3 or higher adverse events were observed. Conclusion: This study demonstrated that 48-week pemafibrate administration improved liver-related enzymes and surrogate marker of liver fibrosis in patients with MASLD. The improvement of insulin resistance by pemafibrate may contribute to the favorable effect on MASLD complicated by dyslipidemia.

Low vitamin D levels accelerates muscle mass loss in patients with chronic liver disease.

Sarcopenia frequently and progressively occurs in patients with chronic liver disease. This study aimed to clarify the relationship between vitamin D levels and muscle mass loss. A total of 166 patients with chronic liver disease were enrolled in this study. Skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis at baseline and after 1 year. The rate of change in SMI from baseline after 1 year was calculated: ΔSMI (%) = [(1-year SMI - baseline SMI) / baseline SMI] × 100. Muscle mass loss was defined as ΔSMI ≤ -2%. The median 25-hydroxyvitamin D was 15.2 (11.2-19.3) ng/mL. The median SMI were 6.8 (5.9-7.8) kg/m2 at baseline and 6.7 (5.9-7.6) kg/m2 after 1 year. The median ΔSMI was -1.23% (-2.21% to 1.61%). Multivariate analysis identified low 25-hydroxyvitamin D as an independent factor associated with muscle mass loss. The optimal cut-off value of 25-hydroxyvitamin D to predict muscle mass loss was 12.7 ng/mL. Muscle mass loss was found in 56.4% v.s. 18.0% of patients with 25-hydroxyvitamin D < 12.7 vs. ≥ 12.7 ng/mL, respectively (p = 9.01 × 10-7); with the highest incidence in patients with non-alcoholic fatty liver disease (NAFLD). Specifically, patients with NAFLD and 25-hydroxyvitamin D < 12.7 ng/mL had a significantly higher incidence of muscle mass loss than those with ≥ 12.7 ng/mL (p = 1.23 × 10-3). Low vitamin D levels are associated with muscle mass loss after 1 year in patients with chronic liver disease, especially NAFLD.

A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C.

Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.

How do the 2022 European Society of Cardiology/European Respiratory Society guidelines modify the diagnosis of portopulmonary hypertension in patients with cirrhosis complicated by portal hypertension? A post hoc analysis.

The vertical and horizontal broken lines indicate the pre-revised criteria, whereas the vertical and horizontal solid lines indicate the 2022 European Society of Cardiology/European Respiratory Society criteria.

Risk factors for portopulmonary hypertension in patients with cirrhosis: a prospective, multicenter study.

BACKGROUND: Tricuspid regurgitation pressure gradient (TRPG) measurement by echocardiography is recommended as the most objective examination to detect portopulmonary hypertension (PoPH). This study aimed to identify factors associated with a high TRPG in patients with cirrhosis and develop a scoring model for identifying patients who are most likely to benefit from echocardiography investigations. RESULTS: A total of 486 patients who underwent echocardiography were randomly allocated to the derivation and validation sets at a ratio of 2:1. Of the patients, 51 (10.5%) had TRPG ≥ 35 mmHg. The median brain natriuretic peptide (BNP) was 39.5 pg/mL. Shortness of breath (SOB) was reported by 91 (18.7%) patients. In the derivation set, multivariate analysis identified female gender, shortness of breath, and BNP ≥ 48.9 pg/mL as independent factors for TRPG ≥ 35 mmHg. The risk score for predicting TRPG ≥ 35 mmHg was calculated as follows: - 3.596 + 1.250 × gender (female: 1, male: 0) + 1.093 × SOB (presence: 1, absence: 0) + 0.953 × BNP (≥ 48.9 pg/mL: 1, < 48.9 pg/mL: 0). The risk score yielded sensitivity of 66.7%, specificity of 75.3%, positive predictive value of 25.5%, negative predict value of 94.3%, and predictive accuracy of 74.4% for predicting TRPG ≥ 35 mmHg. These results were almost similar in the validation set, indicating the reproducibility and validity of the risk score. CONCLUSIONS: This study clarified the characteristics of patients with suspected PoPH and developed a scoring model for identifying patients at high risk of PoPH, which may be used in selecting patients that may benefit from echocardiography.

Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

Antifibrotic effect and long-term outcome of SGLT2 inhibitors in patients with NAFLD complicated by diabetes mellitus.

The aim of this retrospective multicenter study was to clarify the antifibrotic effect and long-term outcome of sodium glucose cotransporter 2 inhibitors (SGLT2-Is) in patients with nonalcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Of the 1262 consecutive patients with T2DM who recently received SGLT2-Is, 202 patients with NAFLD had been receiving SGLT2-Is for more than 48 weeks and were subjected to this analysis. Furthermore, 109 patients who had been on SGLT2-I therapy for more than 3 years at the time of analysis were assessed for the long-term effects of SGLT2-Is. Significant decreases in body weight, liver transaminases, plasma glucose, hemoglobin A1c, and Fibrosis-4 (FIB-4) index were found at week 48. Overall, the median value of FIB-4 index decreased from 1.42 at baseline to 1.25 at week 48 (p < 0.001). In the low-risk group (FIB-4 index < 1.3), there was no significant change in the FIB-4 index. In the intermediate-risk (≥1.3 and <2.67) and high-risk (≥2.67) groups, the median levels significantly decreased from 1.77 and 3.33 at baseline to 1.58 and 2.75 at week 48, respectively (p < 0.001 for both). Improvements in body weight, glucose control, liver transaminases, and FIB-4 index were found at 3 years of SGLT2-I treatment. In the intermediate-risk and high-risk groups (≥1.3 FIB-4 index), the FIB-4 index maintained a significant reduction from baseline throughout the 3 years of treatment. Conclusion: This study showed that SGLT2-Is offered a favorable effect on improvement in FIB-4 index as a surrogate marker of liver fibrosis in patient with NAFLD complicated by T2DM, especially those with intermediate and high risks of advanced fibrosis, and this antifibrotic effect is sustained for the long term.

Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study.

Background and Aim: This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods: This was a single-arm, open-label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24-week trial. Results: Body weight and levels of liver-related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment-insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis-4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1-2 transient gastrointestinal disorders. Conclusions: Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.

Shorter pruritus period and milder disease stage are associated with response to nalfurafine hydrochloride in patients with chronic liver disease.

Nalfurafine hydrochloride, a selective κ-opioid receptor agonist has been approved for pruritus in patients with chronic liver disease. However, not all patients respond to nalfurafine hydrochloride. The aim of this study was to clarify the efficacy of nalfurafine hydrochloride. The subjects were patients with chronic liver disease complicated by pruritus who were treated with nalfurafine hydrochloride between May, 2015, and May, 2021. The degree of pruritus was evaluated based on the Visual Analog Scale (VAS) score and the Kawashima's pruritus score. Nalfurafine hydrochloride 2.5 µg was orally administered once a day for 12 weeks. A decrease in the VAS score of ≥ 25 mm or the Kawashima's pruritus score of ≥ 1 scores was designated as relevant response. The former of ≥ 50 mm or the latter of ≥ 2 scores as remarkable response. The 326 patients who were evaluated the efficacy at 12 weeks. The median time suffering from pruritus to administration of nalfurafine hydrochloride was 4 months. The median VAS score improved from 70.0 mm before administration to 40.0 and 30.0 mm at 4 and 12 weeks of treatment, respectively. On multivariate analysis, shorter itching period and lower FIB-4 index value were extracted as the independent factors related to remarkable responder. On multivariate analysis, shorter itching period was extracted as the only independent factor related to relevant responder. In conclusion, this study suggested nalfurafine hydrochloride treatment markedly improves pruritus in patients with chronic liver disease. A short pruritus period and less-advanced fibrosis were associated with response to nalfurafine hydrochloride.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C.

Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.

Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

Effect of Vitamin D Supplementation on Skeletal Muscle Volume and Strength in Patients with Decompensated Liver Cirrhosis Undergoing Branched Chain Amino Acids Supplementation: A Prospective, Randomized, Controlled Pilot Trial.

BACKGROUND: Sarcopenia worsens patient prognoses in chronic liver disease. This study aimed to elucidate the effects of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated cirrhosis. METHODS: Thirty-three patients were entered into the study based on the criteria and then randomly assigned to two groups: Group A (n = 17), the control group, and Group B (n = 16), those who received oral native vitamin D3 at a dose of 2000 IU once a day for 12 months. RESULTS: SMI values in Group B were significantly increased at 12 months (7.64 × 10-3). The extent of changes in the SMI and grip strength in Group B were significantly greater than that in Group A at 12 months (p = 2.57 × 10-3 and 9.07 × 10-3). The median change rates in the SMI were +5.8% and the prevalence of sarcopenia was significantly decreased from 80.0% (12/15) to 33.3% (5/15; p = 2.53 × 10-2) in Group B. CONCLUSIONS: Vitamin D supplementation might be an effective and safe treatment option for patients with decompensated cirrhosis to increase or restore the skeletal muscle volume and strength or prevent the muscle volume and strength losses.

Effect of sodium-glucose cotransporter 2 inhibitor in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a propensity score-matched analysis of real-world data.

BACKGROUND: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM. METHODS: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors. RESULTS: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1-6.7 kPa) (p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight (p < 0.001), alanine aminotransferase (p = 0.02), uric acid (p < 0.001), and Fibrosis-4 (FIB-4) index (p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group (p < 0.001). CONCLUSION: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.

Development of Interferon-Free, Direct-Acting Antivirals Treatment for Japanese Patients with Chronic Hepatitis C Infection and Chronic Kidney Disease.

Chronic hepatitis C virus (HCV) infection can progress to liver cirrhosis and hepatocellular carcinoma. Interferon-based treatment was previously the only antiviral therapy for chronic hepatitis C infection; however, development of interferon-free, direct-acting antivirals, in 2014, markedly improved treatment efficacy and safety. Treatment indications were expanded to include elderly adults, patients with advanced liver fibrosis, and patients with chronic hepatitis C infection complicated by chronic kidney disease, for whom antiviral therapy had been difficult or contraindicated. The median age of patients with chronic HCV infection in Japan is 70 years, older than in other countries. Because diminished renal function is common in elderly adults, a safe and effective treatment for chronic hepatitis C complicated by chronic kidney disease has been expected in Japan. In addition, the HCV antibody-positive rate is higher in hemodialysis patients than in non-hemodialysis patients in Japan. Numerous studies have reported that direct-acting antivirals are safe and effective for hepatitis C patients on hemodialysis. This review summarizes treatments available in Japanese clinical practice for patients with chronic HCV infection complicated by chronic kidney disease, including hemodialysis patients.

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

Sequential therapy from entecavir to tenofovir alafenamide versus continuous entecavir monotherapy for patients with chronic hepatitis B.

BACKGROUND AND AIM: Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first-line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. METHODS: In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV-TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. RESULTS: From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV-TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (-0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (-0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV-TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. CONCLUSIONS: The present study indicated that the efficacy, especially of the HBsAg-reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV.

Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study.

INTRODUCTION: Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. RESULTS: The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child-Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5-13). The albumin-bilirubin (ALBI) score ranged from - 3.01 to - 0.45 (median - 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child-Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child-Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10-4 and 2.42 × 10-4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. CONCLUSION: Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. TRIAL REGISTRATION: UMIN registration no, 000038587.

Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization.

Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension. METHODS: The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg. RESULTS: The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. CONCLUSIONS: Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.