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Background/Aims Endoscopic resection (ER) for superficial non-ampullary duodenal epithelial tumors (SNADETs) is challenging. Conventional endoscopic mucosal resection (CEMR) is also problematic due to the anatomical features of the duodenum. We compared the safety and efficacy of underwater endoscopic mucosal resection (UEMR) with those of CEMR through a retrospective analysis. Methods Altogether, 44 consecutive patients with 46 SNADETs underwent ER (18 CEMR cases and 28 UEMR cases) between January 2016 and October 2019. We investigated the proportions of en bloc resection, R0 resection, complications, resection time, and total procedure time and compared the outcomes of patients from the CEMR group with those of patients from the UEMR group. Results The median tumor size was 8.0 mm (range, 2.0–20.0 mm). The UEMR group showed a higher proportion of en bloc resection (96.4% vs. 72.2%, p

Currently, there are no reports on the learning curve of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using dedicated plastic stents. Therefore, we evaluated the outcomes of EUS-HGS using dedicated plastic stents at tertiary referral centers during the initial development phase of EUS-HGS.Endoscopic retrograde cholangiopancreatography (ERCP) was strictly prioritized over EUS-HGS. Twenty-three consecutive patients treated using EUS-HGS with a 7-Fr dedicated plastic stent over 4 years beginning in 2018 were analyzed retrospectively.The most common primary disease was pancreatic cancer, and the most common reason for difficulty in ERCP was duodenal obstruction, followed by surgically altered anatomy. The overall technical success rate of EUS-HGS was 95.7% (22/23). One failed case was converted to EUS-guided choledochoduodenostomy. The clinical success rate was 90.9% (20/22). Adverse events (AEs) related to the procedure were observed in four (17.4%) patients, including mild biliary peritonitis in three (13.0%) and mild cholangitis in one (4.3%) patient; all patients received conservative therapy. No serious AEs, such as stent migration, bleeding, or gastrointestinal perforation, were observed. Recurrent biliary obstruction (RBO) was observed in eight (34.8%) patients. Of these, HGS stent replacement was performed in four patients, and other treatments were performed in the remaining four patients. Another four (17.4%) patients did not develop RBO but underwent periodic HGS stent replacement.EUS-HGS using a dedicated plastic stent was performed safely even in its initial phase of introduction. The approach using this stent can be useful in case of ERCP failure for biliary decompression because of the high feasibility and low risk of serious adverse events.

AIM Although some relationships between gut microbiota and liver diseases have been reported, it remains uncertain whether changes in gut microbiota owing to differences in race, food and living environment have similar effects. Response to ursodeoxycholic acid (UDCA) may predict the long-term prognosis of patients with primary biliary cholangitis (PBC); however, little is known about the significance of the gut microbiome in patients with PBC. We elucidated the relationships among clinical profiles, biochemical response to UDCA and gut microbiome composition in patients with PBC. METHODS Fecal samples from 76 patients with PBC treated at our hospital were collected; patients whose UDCA intake period was

Background and Aim Hypothyroidism might play a crucial role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined. Methods This cross‐sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed. Results The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic‐related factors, such as BMI, triglyceride, high‐density lipoprotein‐cholesterol, hypertension, and diabetes. Thyroid‐stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic‐related factors, but free thyroxine (FT4) was not a risk factor. The FIB‐4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB‐4 index ≥2.67 was significantly higher, and the proportion of the FIB‐4 index, Thyroid‐stimulating hormone elevation, even within the euthyroid range, is an independent risk factor of non‐alcoholic fatty liver disease and may have an influence on the progression of liver fibrosis, even with a normal free T4 level.

The prognosis of highly advanced unresectable hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT) is poor. There are currently no reports of long-term survival for up to 5 years in patients with advanced HCC who were treated with sorafenib. We describe a patient with Vp4 HCC who was treated with a sorafenib-based multidisciplinary treatment and experienced long-term survival, which may be the longest survival to date. A man in his late 60 s presented with general fatigue. Eight years previously, he received interferon monotherapy for chronic hepatitis C for 48 weeks and achieved a sustained virological response. He was diagnosed with a PVTT (Vp4) with diffuse-type HCC in the S6 lobe of the liver. He received hepatic arterial infusion of chemotherapy using 5-fluorouracil and cisplatin. Because of the occurrence of adverse effects, he was placed on sorafenib treatment. The treatment was effective and the HCC reduced. However, after 3 years of treatment, a 2-cm HCC was observed in the S5 lobe, and the patient underwent laparoscopic partial hepatectomy. After the operation, he continued to receive sorafenib, with no obvious recurrence, and survived for over 108 months after the first treatment. There are currently no reported cases of long-term progression-free survival by sorafenib for five years in patients of Vp4 HCC. In conclusion, we report a case of longest survival of a patient with Vp4 HCC treated with sorafenib-based multidisciplinary treatment.

Mortality and recurrence rates of hepatocellular carcinoma (HCC) are high. Recent studies show that for patients with HCC beyond up-to-seven criteria, treatment with molecular-targeted agents (MTAs) is recommended because the treatment efficiency of transcatheter arterial chemoembolization (TACE) is poor, further, TACE increases decline in liver function. However, the relationship between TACE and liver function decline in patients with HCC within up-to-seven criteria has not been clarified. Hence, we aimed to investigate this relationship. This retrospective observational study included 189 HCC tumors within up-to-seven criteria in 114 Child–Pugh class A patients. Twenty-four (12.7%) tumors were changed from Child–Pugh class A to B after TACE, and 116 (61.4%) tumors exhibited recurrence within 6 months after TACE. Prothrombin time (PT) and albumin–bilirubin (ALBI) score before TACE were significantly associated with liver dysfunction from Child–Pugh class A to B. The combination of PT and ALBI score before TACE had high predictive ability for liver dysfunction from Child–Pugh class A to B after TACE (specificity = 100%, sensitivity = 91.7%). The combined use of pre-TACE PT and ALBI score has a high predictive ability for liver dysfunction after TACE for Child–Pugh class A patients with HCC within up-to-seven criteria.

Background/Aims: We previously reported the comparable efficacy of bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) to that of sorafenib chemotherapy for the treatment of advanced hepatocellular carcinoma (aHCC) in patients with compensated cirrhosis. In this study, we demonstrate the efficacy of B-HAIC in patients with decompensated cirrhosis. Methods: Forty-five patients with aHCC refractory to transcatheter arterial chemo-embolization (TACE) were treated with B-HAIC and were divided into two groups according to hepatic functional reserve (Child-Pugh grade). Overall survival period, treatment response, and adverse events in each group were analyzed. Results: Efficacy and disease control rates in the Child-Pugh B group (n=24; 21% and 71%, respectively) were not significantly impaired compared the Child-Pugh A group (n=21; 38% and 67%, respectively). Median survival time and survival rate at 12 months in the Child-Pugh B group were 422 days and 58.3%, respectively, whereas those in the Child- Pugh A group were 567 days and 70.8%, respectively. Importantly, the hepatic functional reserve of patients did not worsen in either group during the treatment period. Furthermore, the occurrence rate of adverse events leading to discontinuation of anti-tumor treatment was not significantly increased in the Child-Pugh B group. Conclusions: Given the preservation of hepatic functional reserve afforded by B-HAIC chemotherapy in patients with decompensated cirrhosis, B-HAIC might be an acceptable alternative strategy for aHCC patients who do not respond to TACE. (Clin Mol Hepatol 2019;25:381-389)

AIM To identify laboratory predictors of histological progression (HP) of primary biliary cholangitis (PBC). METHODS Sequential biopsies were carried out on 35 (11.4%) of 308 patients with PBC treated with ursodeoxycholic acid (UDCA). Patients were divided into high γ-glutamyl transpeptidase (GGT) (n = 18) and low GGT (n = 17) groups, based on the median value of GGT at baseline. Patients were then categorized as showing HP (progressive group, PG) or lacking HP (non-progressive group, NPG) according to the Scheuer and Nakanuma classifications, with the latter grading liver fibrosis (fibrosis score) and bile duct loss (BDL score). RESULTS According to the Scheuer definition, 12 patients had HP and 23 did not. According to the Nakanuma definition, 8 and 27 patients were in the PG and NPG groups, respectively. The fibrosis and BDL scores progressed in 13 and 8 patients, respectively, whereas 22 and 25 patients did not show HP, respectively. Fisher's exact probability test analysis revealed that the rate of HP using the Nakanuma fibrosis score was significantly higher in the high GGT group compared to the low GGT group (P

We aimed to prospectively identify the risk factors of sarcopenia in patients with cirrhosis. Patients (n = 193) included in a discovery cohort (January 2011 and December 2014) were categorized into alcoholic (A1; n = 55) and non-alcoholic cirrhosis (NA; n = 138) groups, and those (n = 235) in a validation cohort (January 2015 to December 2019) were categorized into alcoholic (n = 92), non-alcoholic steatohepatitis-related (n = 27), and hepatitis C virus-related cirrhosis groups (n = 116). Skeletal muscle mass index (SMI) was determined using computed tomography (SMI-CT) and bioelectrical impedance analysis (SMI-BIA). Endotoxin activity (EA) was measured with an EA assay. SMI-CT correlated with grip strength in all the groups but significantly correlated with SMI-BIA of the men in group A1 (R = 0.64, P

ObjectivesThis study aimed to evaluate and compare the outcomes of palliative endoscopic biliary stenting (EBS) and complete stone removal among elderly patients with choledocholithiasis using propensity score matching.MethodsFrom April 2012 to October 2017, 161 patients aged 75 years and older with choledocholithiasis underwent endoscopic retrograde cholangiopancreatography at our institution. Among them, 136 (84.5%) had complete stone removal, and 25 (15.5%) underwent palliative EBS without further intervention until symptom occurrence. The median age of the EBS group was significantly higher than that of the complete stone removal group. The proportion of patients with dementia, cerebral infarction, preserved gallbladder with gallstones, and surgically altered anatomy was higher in the EBS group than in the complete stone removal group. Propensity score matching was used to adjust for different factors. In total, 50 matched patients (n = 25 in each group) were analyzed.ResultsThe median duration of cholangitis-free periods was significantly shorter in the EBS group (596 days) than in the complete stone removal group. About half of patients in the EBS group required retreatment and rehospitalization for cholangitis during the observation period. Cholangitis was mainly caused by stent migration. There was no significant difference in terms of mortality rate and procedure-related adverse events between the two groups. Death was commonly attributed to underlying diseases. However, one patient in the EBS group died due to severe cholangitis.ConclusionsPalliative EBS should be indicated only to patients with choledocholithiasis who have a poor prognosis.

Background: This study aimed to compare the diagnostic performance of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (γ-GTP) to assess the single and combined benefits of these biological markers for the detection of chronic excessive alcohol consumption in patients with alcoholic cirrhosis. Methods: Biological markers were determined in blood samples from patients with alcoholic cirrhosis (drinking group, n = 35, nondrinking group, n = 81). The prediction accuracy of %CDT alone, γ-GTP alone, and their combination for the detection of excessive alcohol consumption was determined in patients with alcoholic cirrhosis. Results: Serum total bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-GTP, and alkaline phosphatase levels and %CDT were significantly higher and serum albumin levels were significantly lower in the drinking group than in the nondrinking group. The combination of %CDT and γ-GTP compared with %CDT or γ-GTP alone showed a higher prediction accuracy. The combination of %CDT and γ-GTP exhibited a higher specificity than γ-GTP alone. However, in terms of sensitivity, no significant difference was found between single or combined markers. Conclusions: The combination of %CDT and γ-GTP is considered a useful biomarker of chronic excessive alcohol consumption in patients with alcoholic cirrhosis.

Background/Aims: Covered self-expandable metallic stents (CMSs) are widely used for malignant distal biliary obstructions (MDBOs) caused by pancreatic carcinoma. This study compared the efficacy and safety of the laser-cut-type and braided-type CMSs.Methods: To palliate MDBOs caused by pancreatic carcinoma, the laser-cut-type CMSs was used from April 2014 to March 2017, and the braided-type CMSs was used from April 2017 to March 2019. The tested self-expandable metallic stents were equipped with different anti-migration systems.Results: In total, 47 patients received CMSs for MDBOs (24 laser-cut type, 23 braided-type). The time to recurrent biliary obstruction (TRBO) was significantly longer in the braided-type CMSs (p=0.0008), and the median time to stent dysfunction or patient death was 141 and 265 days in the laser-cut-type CMSs and braided-type CMSs, respectively (p=0.0023). Stent migration was the major cause of stent dysfunction in both groups, which occurred in 37.5% of the laser-cut-type CMSs and 13.0% of the braidedtype CMSs. There were no differences in the survival duration between the groups.Conclusions: The TRBO was significantly longer for the braided-type CMSs with an anti-migration system than for the laser-cuttype. Stent migration tended to be less frequent with the braided-type CMSs than with the laser-cut-type CMSs.

This large multicenter randomized controlled trial compared the diagnostic yields of 22-gauge standard and 22-gauge Franseen needles for EUS-guided tissue acquisition (EUS-TA) of solid pancreatic lesions.Consecutive patients with solid pancreatic lesions were prospectively randomized to EUS-TA using standard or Franseen needles. Samples obtained with the first needle pass and with second and subsequent passes were evaluated separately. The primary endpoint was the rate of accuracy for diagnosis of malignancy. Other endpoints were technical success rate, sample cellularity, adverse events, diagnostic accuracy in patient subgroups, and the diagnostic accuracy and numbers of second and subsequent needle passes.Of 523 patients undergoing EUS-TA, 260 were randomized to using standard 22-gauge needles and 263 to 22-gauge Franseen needles. The technical success rate in each group was 99.6%, with similar adverse event rates in the standard (1.5%) and Franseen (.8%) needle groups. First-pass EUS-TA using the Franseen needle resulted in significantly greater diagnostic accuracy (84.0% vs 71.2%, P .001) and sensitivity (82.4% vs 66.7%, P .001) than first-pass EUS-TA using a standard needle and also resulted in superior diagnostic accuracy in patients requiring immunostaining. Second and subsequent EUS-TA using Franseen needles showed significantly greater accuracy (94.7% vs 90.0%, P = .049) and sensitivity (94.0% vs 88.6%, P = .047) and required fewer needle passes (1.81 vs 2.03, P = .008) than using standard needles.EUS-TA with the Franseen needle is superior to EUS-TA with a standard needle with respect to diagnostic accuracy per pass, particularly in patients who require immunostaining, and number of passes when using macroscopic on-site evaluation. (Clinical trial registration numbers: UMIN000030634 and jRCTs052180062.).

A potential restriction of the Baveno VI consensus, which helps to avoid unnecessary endoscopies, is the limited availability of FibroScan. We aimed to identify serum fibrosis indices that might aid in ruling out the presence of high-risk varices in cirrhotic patients. This retrospective study included 541 consecutive patients with cirrhosis who underwent endoscopy and had data available for nine serum fibrosis indices, including platelet count, hyaluronic acid, 7S fragment of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, fibrosis index based on four factors (FIB-4), aspartate transaminase/platelet ratio index and enhanced liver fibrosis score. Optimal index cutoffs for predicting high-risk varices were calculated in an estimation cohort (n = 127) and evaluated in a validation cohort (n = 351). The diagnostic performance of the indices was assessed by receiver operating characteristic curve analysis. In the estimation cohort, a FIB-4 cutoff of 2.78 provided the greatest diagnostic accuracy in predicting both all-grade and high-risk varices. FIB-4 had a negative predictive value of 1.00 for high-risk varices in both cohorts, and 21.3% (27/127) and 14.8% (52/351) of the estimation and validation cohorts, respectively, avoided esophagogastroduodenoscopy, no high-risk varices were missed in either cohort. FIB-4 correctly identifies the absence of high-risk varices in patients with cirrhosis. Therefore, those with a FIB-4 of &ge, 2.78 should undergo esophagogastroduodenoscopy, and FIB-4 determination should be recommended every 6&ndash, 12 months concurrently with the other blood tests until the index value reaches 2.78 in those with a FIB-4 of &lt, 2.78.

Background/Aims: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. Methods: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. Results: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. Conclusions: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.

Aim Proton pump inhibitors (PPIs) are frequently prescribed in patients with cirrhosis, but this therapy entails potential complications. We aimed to investigate the influence of PPI use on intestinal permeability in patients with cirrhosis. Methods We recruited 228 patients with cirrhosis and divided them into four groups. Group (Gp)1 comprised patients receiving a PPI with concurrent neomycin (NEO) (PPI-NEO group, n = 14 [6.1%]), Gp2 and Gp3 comprised those receiving either PPI or NEO (PPI group, n = 91 [39.9%]; and NEO group, n = 11 [4.4%]), and Gp4 comprised those receiving neither of these medications (control group; n = 112 [49.1%]). We assessed the intestinal permeability by measuring endotoxin activity (EA) using a luminol chemiluminescence method. Results Endotoxin activity levels were significantly higher in patients with Child B cirrhosis than in those with Child A cirrhosis, but we found no significant differences in EA levels between patients with Child C cirrhosis and those with either Child A or B cirrhosis. We observed no significant differences in EA levels among groups 1-4. Patients without antibiotic exposure (n = 203), comprising 91 patients on PPI therapy (Gp2) and 112 no-PPI-therapy controls (Gp4), were subdivided according to Child-Pugh (CP) classification. We found no significant differences in EA levels between Gp2 and Gp4 in either CP class. Conclusion Our results suggest that PPI usage does not have a significant impact on serum levels of gut-derived endotoxins, which are already elevated because of the increased intestinal permeability in patients with cirrhosis.

The presence of bridging fibrosis predicts survival of primary biliary cholangitis (PBC). This study aimed to compare serum parameters for the estimation of liver fibrosis and prediction of clinical outcomes in PBC. Out of 392 patients with PBC, 102 who underwent liver biopsy and in whom fibrosis indices, platelet count, hyaluronic acid, type IV collagen 7 second domain, procollagen type III amino-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, N-terminal type III collagen propeptide levels; fibrosis index based on 4 factors, aspartate aminotransferase-to-platelet ratio index, and enhanced liver fibrosis (ELF) score were determined, were included. The correlation of histological stages based on both Scheuer and Nakanuma classifications with fibrosis indices was investigated. The Nakanuma system comprises grading for liver fibrosis and bile duct loss. Diagnostic performances of 10 fibrosis indices were evaluated to identify patients with poor prognosis. Moreover, correlations of those with PBC clinical manifestation and survival were also investigated. Enhances liver fibrosis (ELF) score had the highest correlation coefficient for liver fibrosis evaluated according to either the Scheuer or Nakanuma classification among 10 serum fibrosis indices. It also had the highest diagnostic performance in estimating Scheuer stage III and Nakanuma fibrosis score 2, both of which represent portal-bridging fibrosis. Patients with an ELF score of ≥10.0 had shorter survival and presented more frequently clinical complications than those with an ELF score of

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (&Delta, sCD163: Correlation coefficient (R) = 0.680, p = 0.023, &Delta, sMR: R = 0.613, p = 0.014, vs. &Delta, EA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.

Background and study aims Short-type single-balloon enteroscope (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is a promising alternative treatment in postsurgical altered anatomy. However, it is technically demanding, and factors affecting its technical difficulty have not yet been clarified. This study aimed to examine the procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure. Patients and methods A total of 117 consecutive patients (203 procedures) with surgically altered anatomy underwent ERCP using prototype short SBEs. The procedural success rate of short SBE-assisted ERCP and the potential factors affecting procedural failure were examined retrospectively. Results The enteroscopy success rate and procedural success rate were 92.6 % (95 % confidence interval [CI] 88.1 % – 95.8 %) and 81.8 % (95 %CI 75.8 % – 86.8 %), respectively. Multivariate analyses indicated that pancreatic indication (odds ratio [OR] 4.35, 95 %CI 1.67 – 11.4), first ERCP attempt (OR 6.03, 95 %CI 2.17 – 16.8), and no transparent hood (OR 4.61, 95 %CI 1.48 – 14.3) were potential risk factors for procedural failure. Conclusions Short SBE-assisted ERCP was effective in postsurgical altered anatomy. This large case series suggested the potential factors affecting procedural failure.

Despite the availability of molecularly targeted agents for advanced hepatocellular carcinoma (aHCC), these are limited to compensated cirrhotic patients, and concerns about decreased hepatic functional reserve (HFR) and unknown adverse events, which may affect long-term survival, remain unaddressed. In this study, we enrolled 96 aHCC patients treated with bimonthly hepatic arterial infusion chemotherapy (B-HAIC) with cisplatin or sorafenib monotherapy (oral sorafenib 400 mg twice daily) not only to demonstrate its efficacy and significance but also to indicate preferable candidates by setting a response-related biomarker. Differences in treatment had no significant effect on overall survival (OS). The response rate in patients treated with B-HAIC was relatively higher than those treated with sorafenib. HFR was well maintained over the treatment course with B-HAIC, while it was significantly impaired with sorafenib. By employing multivariate analysis, we found negative trends between progression-free survival (PFS) periods and serum levels of alpha fetoprotein as well as des-gamma-carboxy prothrombin (DCP). In addition, a logistic regression analysis of the relationship between serum DCP levels and PFS periods over 420 days (14 months) showed that the PFS periods of patients with higher DCP was significantly shorter than those of patients with lower DCP (p = 0.02). Subsequently, the present study demonstrated the efficacy and safety of B-HAIC and identified a predictor of unpreferable patients. Based on these results, B-HAIC might be an alternative treatment after the implementation of new molecularly targeted therapies.

L-carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) is the physiologically active form of carnitine and is a natural compound that has been shown to exhibit antioxidant activity. L-carnitine is used as a supplementary treatment in patients with cirrhosis with hepatic encephalopathy, hyperammonemia or muscle cramps. In the present study, the effect of L-carnitine supplementation on health-related quality of life in 30 patients with cirrhosis was prospectively examined. L-carnitine (1,800 mg/day) was administered orally for 6 months. To assess the effects of L-carnitine on chronic fatigue, patients filled out a self-report questionnaire regarding their physical and mental health. The levels of total and free carnitine, and acylcarnitine were found to be significantly higher 1, 3 and 6 months after therapy initiation compared with before treatment. Serum albumin levels were significantly increased 3 and 6 months after initiation of therapy. L-carnitine supplementation significantly increased the BAP/d-ROM ratio, a marker of antioxidant status in patients with cirrhosis. Changes in serum carnitine concentrations were positively correlated with changes in serum albumin levels (R2=0.369; P=0.012), but not with changes in serum ammonia levels (R2= 0.005; P=0.78). Total and mental health scores improved significantly, and physical scores improved marginally 3 and 6 months after initiation of L-carnitine. These findings may be attributed to the enhanced serum albumin levels and oxidative stress rather than the reduced serum ammonia levels. Based on these results, it is suggested that L-carnitine can potentially alleviate chronic fatigue, along with the increased BAP/d-ROM ratio, which were involved in increased oxidative stress in patients with cirrhosis. The specific mechanisms by which L-carnitine ameliorates chronic fatigue is not fully understood and requires further investigation.

Depression is a major reason for interferon (IFN) therapy cessation. IFN-free direct-acting antiviral (DAA) therapy for depression is not well-documented. Thus, four different IFN-free regimens were assessed in genotype-1 hepatitis C virus (HCV) patients with depression. Overall, 287 HCV genotype-1 patients who received combination therapies with IFN-free DAAs of daclatasvir/asunaprevir (DCV/ASV) (n=84), sofosbuvir/ledipasvir (SOF/LDV) (n=95), ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) (n=74), and elbasvir/grazoprevir (EBR/GZR) (n=34) were included. Treatment-induced depression as a complication of HCV therapy in IFN-free DAA regimens was assessed. The severity of depression was evaluated using the Beck Depression Inventory-II (BDI-II) questionnaire. It was demonstrated that all four DAA regimens achieved similar high efficacy in Japanese patients with HCV genotype-1 infection. Moreover, in seven patients with depression who received the 24-week DCV/ASV treatment regimen, the BDI-II scores significantly increased at week 4 as compared with pretreatment values; furthermore, they decreased below baseline at week 12 despite the rapid decline of serum HCV levels after the initiation of DCV/ASV therapy. The BDI-II scores gradually decreased during therapy in the remaining 77 DCV/ASV-treated patients without depression. The BDI-II scores showed a significant decrease from baseline to the end of treatment with 12-week regimens, including SOF/LDV and EBR/GZR. The 12-week DAA regimen of SOF/LDV and EBR/GZR can be safely used with high efficacy in patients with genotype-1 HCV infection, including those with depression.