Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab.

INTRODUCTION: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. METHODS: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. RESULTS: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. CONCLUSION: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). METHODS: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. RESULTS: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. CONCLUSION: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma.

INTRODUCTION: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. METHODS: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. RESULTS: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. CONCLUSION: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.

BACKGROUND: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. METHODS: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. RESULTS: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors. CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population.

Several studies reported that autoimmune diseases share a number of susceptibility genes. Of these genes, a SNP rs7708392 in TNIP1 was reported to be associated with systemic lupus erythematosus (SLE). Autoimmune hepatitis (AIH), a rare chronic progressive liver disease, shares some clinical features with SLE. Therefore, we investigated whether the SNP is associated with Japanese AIH. An association study of rs7708392 was conducted in 343 Japanese AIH patients and 828 controls. We found that rs7708392 is associated with AIH (P = 0.0236, odds ratio (OR) 1.26, 95% confidence interval (CI): 1.03-1.54), under the allele model for C allele. Significant differences of clinical characteristics of the AIH patients with or without G allele of rs7708392 were not detected. Of interest, the association was stronger in AIH without HLA-DRB1*04:05 allele (P = 0.0063, Q = 0.0127, OR 1.48, 95% CI: 1.12-1.96), though the association was not detected in AIH with DRB1*04:05. The C allele of rs7708392 was associated with AIH, especially AIH without DRB1*04:05, an already established risk factor.

Association of a single nucleotide polymorphism upstream of ICOS with Japanese autoimmune hepatitis type 1.

Autoimmune hepatitis (AIH) is an uncommon chronic autoimmune liver disease. Several studies reported the association of polymorphisms between CD28, CTLA4 and ICOS gene cluster in 2q33.2 with autoimmune or inflammatory diseases. The previous genome-wide association study on type 1 AIH in a European population has reported a risk G allele of a single nucleotide polymorphism (SNP), rs4325730, in this region. Here, we conducted an association study of this SNP with type 1 AIH in a Japanese population, as a replication study.An association study of rs4325730 was conducted in 343 Japanese AIH patients and 315 controls.We found that rs4325730 is associated with AIH (P=0.0173, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.05-1.62, under the allele model for G allele, P=0.0070, OR 1.62, 95% CI 1.14-2.31, under the dominant model for G allele). This SNP was strongly associated with definite AIH (P=0.0134, OR 1.36, 95% CI 1.07-1.74; under allele model for G, P=0.0035, OR 1.85, 95% CI 1.22-2.81, under dominant model for G).This is the first replication association study of rs4325730 upstream of ICOS with AIH in the Japanese population and rs4325730G is a risk allele.

Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus.

AIM: A genome-wide association study revealed that the single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent pilot studies investigated the effects of dipeptidyl peptidase-4 inhibitors on liver function and glucose metabolism in NAFLD with type 2 diabetes mellitus (DM). We herein evaluated the efficacy of alogliptin in NAFLD patients with type 2 DM as well as the relationship between genotypes at rs738409 in PNPLA3 and treatment efficacy. METHODS: Forty-one biopsy-proven NAFLD patients with type 2 DM treated with 25 mg/day alogliptin were retrospectively enrolled. SNP rs738409 in PNPLA3 was present in all patients. Clinical data were measured before and after the treatment. RESULTS: Average hemoglobin A1c (HbA1c) levels mostly remained unchanged. Moreover, significant changes were not noted in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the follow-up period. A positive correlation was observed between improvements in HbA1c (ΔHbA1c) levels and changes in AST (ΔAST) and ALT (ΔALT) levels (r = 0.325 and 0.439, respectively). Patients with the risk allele (G-allele) showed more positive correlation between ΔHbA1c and changes in transaminase. Furthermore, improvements in the levels of total cholesterol, triglycerides and hyaluronic acid were significantly greater in G-allele patients in the weight loss group. CONCLUSION: The treatment of NAFLD with type 2 DM with alogliptin contributed to the amelioration of NAFLD. Our results suggested that differences in the PNPLA3 risk allele affected the therapeutic effects of this treatment.

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

OBJECTIVE: Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. METHODS: A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. RESULTS: Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. CONCLUSION: Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. KEY POINTS: • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

Efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis in patients with liver cirrhosis.

AIM: To assess the efficacy and safety of the anticoagulant drug, danaparoid sodium, in the treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis. METHODS: A consecutive 26 cirrhotic patients with PVT were enrolled in this retrospective cohort study. The etiologies of cirrhosis were hepatitis B virus-related, hepatitis C virus-related, alcoholic and cryptogenic in five, 14, three and four patients, respectively. Child-Pugh grade A, B and C was noted in 13, eight and five patients, respectively. Patients were treated with 2 weeks' administration of danaparoid sodium followed by the evaluation of PVT reduction and adverse events. RESULTS: All patients experienced reduction of PVT through the treatment. The median volume of PVT before and after treatment was 2.40 cm(3) (range, 0.18-16.63) and 0.37 cm(3) (range, 0-5.74), respectively. The median reduction rate of PVT volume was 77.3% (range, 18-100%). According to the reduction rate, complete reduction (CR), partial reduction (PR, ≥50%) and stable disease (SD, <50%) were observed in four (15%), 16 (62%) and six patients (23%), respectively. The median volume of PVT before treatment was significantly different between CR + PR and SD (2.09 vs 4.35 cm(3) , P = 0.045). No severe adverse events such as bleeding symptoms (e.g. gastrointestinal bleeding and cerebral hemorrhage) and thrombocytopenia were encountered. CONCLUSION: Danaparoid sodium for the treatment of PVT in patients with liver cirrhosis was safe and effective. Therefore, anticoagulation therapy with danaparoid sodium could have potential as one of the treatment options in PVT accompanied by cirrhosis.

Disseminated carcinomatosis of the bone marrow originating from hepatocellular carcinoma. A case report.

A 50-year-old male patient was admitted to the hospital for persistent high fever and back pain. He was diagnosed with hepatocellular carcinoma (HCC), bone marrow metastasis and disseminated intravascular coagulation (DIC). Despite the diagnosis and treatment, the general condition deteriorated rapidly and he died of cerebral hemorrhage associated with generalized bleeding tendency. Autopsy showed multiple HCC in the liver and systemic metastasis including bone marrow. The case describes a rare complication of HCC with disseminated carcinomatosis of the bone marrow (DCBM) complicated with DIC, with rapid deterioration and death. This is the first case of DCBM from HCC. Physicians need to be aware of DCBM in patients with HCC.

Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

AIM: To evaluate the response, survival and safety on 3-D conformal radiotherapy (3D-CRT) for major portal vein tumor thrombosis (PVTT) combined with hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 83 advanced HCC patients treated with HAIC who met the following criteria were enrolled: (i) PVTT of the main trunk or first branch of the portal vein; (ii) no extrahepatic metastasis; (iii) Child-Pugh score of 5-7; (iv) performance status of 0 or 1; and (v) no history of sorafenib treatment. The response, overall survival (OS), time to treatment failure (TTF), post-progression survival (PPS) and safety were compared between HAIC combined with 3D-CRT for PVTT (RT group, n = 41) and HAIC alone (non-RT group, n = 42). RESULTS: The objective response of PVTT was significantly higher in the RT group (56.1%) than in the non-RT group (33.3%), while that of intrahepatic tumor and OS were not significantly different between groups. Median OS, TTF and PPS were significantly longer in the RT group than in the non-RT group (8.6 and 5.0 months, 5.0 and 2.7 months, and 5.3 and 1.5 months, respectively) among intrahepatic tumor non-responders to HAIC, whereas those were not significantly different between groups among intrahepatic tumor responders to HAIC. By multivariate analysis, the combination of 3D-CRT with HAIC was an independent contributing factor for OS (hazard ratio, 3.2; 95% confidence interval, 1.692-6.021; P < 0.001) among intrahepatic HCC non-responders to HAIC. CONCLUSION: 3D-CRT for PVTT combined with HAIC could provide survival benefit to non-responder to HAIC.

Major predictors of portal hypertensive enteropathy in patients with liver cirrhosis.

BACKGROUND AND AIM: Portal hypertensive enteropathy (PHE) is acknowledged as a source of bleeding, and predicting its presence has become more important. We assessed PHE using capsule endoscopy (CE) and investigated factors that may predict its presence, including portosystemic shunts (PSs). METHODS: We analyzed data from 134 consecutive patients with liver cirrhosis, from February 2009 to September 2013. All patients had undergone dynamic computed tomography and esophagogastroduodenoscopy before CE examination. The frequencies and types of PHE lesions, and the relationships between the presence of PHE and patients' clinical characteristics were evaluated. The distribution of the lesions was also determined. RESULTS: PHE was found in 91 (68%), erythema in 70 (52%), erosions in 25 (19%), angioectasia in 24 (18%), villous edema in 18 (13%), and varices in 10 (7%) patients. Most lesions were located in the jejunum. The clinical characteristics associated with the presence of PHE were a Child-Pugh grade of B or C (P = 0.0058), and the presence of PSs (P < 0.0001), ascites (P = 0.0017), portal thrombosis (P = 0.016), esophageal varices (P = 0.0017), and portal hypertensive gastropathy (P = 0.0029). The presence of PSs was an independent predictor of PHE (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.27-7.95). Among the shunt types, left gastric vein (OR: 5.31; 95% CI: 1.97-17.0) and splenorenal shunts (OR: 4.26; 95% CI: 1.29-19.4) were independent predictors of PHE. CONCLUSION: PSs, especially left gastric vein and splenorenal shunts, appear to reliably predict the presence of PHE.

Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of response evaluation criteria in solid tumors and tumor markers.

BACKGROUND AND AIM: To assess the early response and outcome of hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC). METHODS: One hundred sixty-five HCC patients treated with HAIC were reviewed retrospectively. The early response to one course of HAIC treatment was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) and changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). RESULTS: The median survival time (MST) for all patients was 9.5 months. The early imaging response by RECIST was assessed as partial response (PR), stable disease (SD), and progressive disease (PD) in 32 (19.3%), 86 (52.1%), and 47 (28.4%) patients, respectively. Survival correlated with early imaging response (MST in PR, 20.6; SD, 11.4; PD, 5.0 months; P < 0.0001). The MST was also significantly different in patients with AFP ratio of ≤ 1 or > 1 and DCP ratio of ≤ 1 or > 1 (worst MST, 6.5 months in patients with AFP ratio of > 1 and DCP ratio of > 1). Among patients with SD early imaging response, patients with AFP ratio of > 1 and DCP ratio of > 1 had significantly poorer survival than others (MST 7.4 vs. 12.6 months, P = 0.014). The decrease in AFP and DCP in the early stage treatment with HAIC were identified as significant and independent factors associated with survival of not only all patients, but also patients with SD early imaging response. CONCLUSION: The use of the combination of RECIST and tumor marker ratio could be useful for assessment of the early response to HAIC and prognosis of patients with advanced HCC.

Non-invasive assessment of liver steatosis in non-alcoholic fatty liver disease.

AIM: The diagnosis of non-alcoholic fatty liver disease (NAFLD) is based on the histological findings. Further, there may be interobserver differences. Liver to spleen (L/S) ratio on computed tomography (CT) is employed to detect or even quantify the fat content of the liver. The objective of this study was to accurately diagnose fatty liver by evaluating the relationship between L/S ratio and histological findings. METHODS: Sixty-seven biopsy-proven NAFLD patients were enrolled. L/S ratio on CT was calculated. The area of steatosis in liver specimens was measured by BIOREVO BZ-9000 microscope, and the percentage of steatosis was calculated using Dynamic cell count BZ-H1C software. RESULTS: Steatotic grade assessed by pathologist was significantly correlated with the percentage of steatosis and L/S ratio. Factors associated with steatosis were L/S ratio, aspartate aminotransferase and Homeostasis Model of Assessment - Insulin Resistance as determined by multivariate analysis. L/S ratios were: S0, 1.16 ± 0.20 (mean ± standard deviation); S1, 0.88 ± 0.28; S2, 0.76 ± 0.20; and S3, 0.40 ± 0.18, respectively. The optimal cut-off value of L/S ratio to exclude steatosis was 1.1, and the area under the receiver-operator curve for the diagnosis of steatosis was 0.886. CONCLUSION: Our study suggests that while 0% of steatosis showed 1.296 L/S ratio, the cut-off value of L/S ratio would be 1.1 at least to exclude clinically important liver steatosis.

Percutaneous transvenous embolization for portosystemic shunts associated with encephalopathy: Long-term outcomes in 14 patients.

AIM: To evaluate the clinical outcomes of percutaneous transvenous embolization (PTE) for portosystemic shunt (PSS) associated with encephalopathy METHODS: Fourteen patients with portosystemic encephalopathy (PSE) were enrolled in this retrospective cohort study. We evaluated technical success, clinical success, complication and outcomes. RESULTS: In cases in which PSS was one of main causes of PSE, three also had splenorenal shunts, four gastrorenal shunts, four superior mesenteric vein systemic shunts, one inferior mesenteric vein systemic shunt and two main trunk of portal vein inferior vena cava shunts. We used only ethanolamine oleate (EO) in five; EO and coils in five; EO, coils and n-butyl 2-cyanoacrylate (NBCA) in two; and coils and NBCA in two patients as embolic materials. The rate of primary and secondary technical success was 93% (13/14 patients) and 100%, respectively. No major complications were encountered related to PTE. Follow-up period was a median of 27 months (range, 12-79). All patients had sustained disappearance of PSE. PSE recurred in one patient because of another PSS development. Thus, clinical success was achieved in 93% (13/14 patients). The ammonia levels 1 year after PTE were significantly improved compared with pre-PTE (median, 102 vs 41 µmol/L) and maintained lower levels 2 and 3 years later. Child-Pugh scores did not change significantly. Esophageal varices were aggravated in 29% (4/14 patients). Five patients died, but no death of hepatic failure related to PTE was encountered. CONCLUSION: PTE could be one of the useful treatment options for PSE.

Clinical outcome and prognostic factors of patients with hepatocellular carcinoma and extrahepatic metastasis treated with sorafenib.

AIM: The purpose of this study was to assess the clinical outcome and identify prognostic factors following treatment of patients with advanced hepatocellular carcinoma (HCC) and extrahepatic metastasis with sorafenib. METHODS: Sixty-one HCC patients with extrahepatic metastasis who were treated with sorafenib were enrolled in this retrospective cohort study. RESULTS: The median survival time (MST) of all patients was 11 months. The median time to radiological progression was 4.2 months. The response rates (complete response [CR] + partial response [PR]) by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were 3.0% and 8.0%, respectively, while the disease control rates (CR + PR + stable disease) were 49% and 49%, respectively. Multivariate analysis identified T factor (intrahepatic tumor stage, T 0-2), response to disease control and des-γ-carboxy prothrombin (<2600 mAU/mL) as significant and independent determinants of survival. Intrahepatic tumor stage before treatment allows stratification of prognosis of patients treated with sorafenib. Four T0 patients remained alive. The MST of patients with T1 (n = 6), T2 (n = 10), T3 (n = 23) and T4 (n = 18) of intrahepatic tumor stage was 20, 23, 7 and 5 months, respectively. Among the progressive disease group, patients with T0-2 intrahepatic tumor stage had better prognosis than patients with T3-4. CONCLUSION: In HCC patients with extrahepatic metastasis who are treated with sorafenib, intrahepatic tumor stage was a significant and independent prognostic factor.

Interferon lambda 4 polymorphism affects on outcome of telaprevir, pegylated interferon and ribavirin combination therapy for chronic hepatitis C.

AIM: The predictive value of the recently identified interferon-λ (IFNL)4 polymorphism on the outcome of telaprevir (TVR), pegylated interferon (PEG IFN) plus ribavirin (RBV) combination therapy for chronic hepatitis C is unknown. METHODS: We assessed predictive factors for sustained virological response (SVR) for TVR, PEG IFN plus RBV combination therapy in 283 genotype 1 chronic hepatitis C patients. IFNL4 polymorphism ss469415590 was analyzed by Invader assay. RESULTS: SVR rates for patients with IFNL4 TT/TT genotype were significantly higher than for those with the IFNL4 TT/ΔG or ΔG/ΔG genotypes (93% and 59%, respectively, P < 0.0001). In a multivariate regression analysis, prior treatment history (treatment-naïve patients or patients who relapsed during prior treatment) (odds ratio [OR], 2.385; P = 0.028), rapid virological response (OR, 6.800; P < 0.0001) and ss469415590 TT/TT genotype (OR, 8.064; P < 0.0001) were identified as significant independent predictors for SVR. In patients with IFNL4 TT/ΔG or ΔG/ΔG genotypes, SVR rates for non-RVR patients were significantly lower than RVR patients (22% and 75%, respectively, P < 0.0001). CONCLUSION: Analysis of IFNL4 polymorphism is a valuable predictor in patients receiving TVR triple therapy.

Non-invasive liver fibrosis score calculated by combination of virtual touch tissue quantification and serum liver functional tests in chronic hepatitis C patients.

AIM: Acoustic radiation force impulse (ARFI) technology, involving the shear wave velocity (SWV) with virtual touch tissue quantification (VTTQ), are currently available for the assessment of liver fibrosis, while there is no index derived from the combination of SWV and blood tests. The aim of this study was to develop a new index for assessment of liver fibrosis. METHODS: The subjects were 176 consecutive patients with hepatitis C (training set [n = 120] and validation set [n = 56]) who underwent liver biopsy in our institution. RESULTS: In the training set, SWV, international normalized ratio (INR) and alanine aminotransferase (ALT) correlated independently and significantly with fibrosis. According to this, we developed the VIA index = -1.282 + 0.965 × SWV + 1.785 INR + 0.00185 ALT. The areas under the receiver-operator curve (AUROC) of the VIA index were 0.838 for the diagnosis of significant fibrosis (≥F2), 0.904 for the severe fibrosis (≥F3) and 0.958 for the cirrhosis (F4) in the training set. While in the validation set, AUROC of the VIA index were 0.917 for F2 or higher, 0.906 for F3 or higher and 1.000 for F4, respectively. AUROC of the VIA index was improved compared to SWV alone, equivalent for VIA for the diagnosis of F2 or higher, and superior to that of FIB-4 index and aspartate aminotransferase-to-platelet ratio index for the diagnosis of F3 or higher and F4. CONCLUSION: The VIA index is potentially more useful for assessment of liver fibrosis than SWV alone, and easily and accurately measures liver fibrosis stage.

Is small-bowel capsule endoscopy effective for diagnosis of esophagogastric lesions related to portal hypertension?

BACKGROUND AND AIM: Effectiveness of capsule endoscopy (CE) for screening the small bowel in patients with portal hypertension (PHT) has been reported. However, few reports discuss CE detection of specific esophagogastric lesions related to PHT. Thus, we assessed whether CE is useful for detecting such lesions. METHODS: One hundred nineteen consecutive patients with PHT comprised the study group. All had undergone esophagogastroduodenoscopy (EGD) prior to CE. The diagnostic yield of CE for esophageal varices (EVs), gastric varices (GVs), and portal hypertensive gastropathy (PHG) was evaluated. In addition, diagnostic yield in relation to form, location of the varices, grade, and extent of PHG was evaluated. RESULTS: EVs were found by EGD in 71 patients. The overall diagnostic yield of CE for EVs was 72% (51/71). The diagnostic yield was significantly greater for F2/F3 EVs than for F1 EVs (87% vs 61%, P = 0.03). The diagnostic yield was significantly greater for Lm/Ls EVs than for Li EVs (85% vs 55%, P = 0.01). The diagnostic yield was significantly greater for locus superior/locus medialis EVs than for locus inferior EVs (85% vs 55%, P = 0.01). GVs were found by EGD in 29 patients. Only one case was detected by CE. PHG was found by EGD in 35 patients. The diagnostic yield of CE for PHG was 69% (24/35). There was no difference in diagnostic yield between cases of severe and mild PHG (82% vs 63%, P = 0.44). Diagnostic yield of CE for PHG in the gastric body was significantly greater than that in the fundus (100% vs 48%, P = 0.0009). CONCLUSION: CE is reliable for diagnosis of F2/F3 and/or Lm/Ls EVs and of PHG in the gastric body.

Long-term outcome of patients with gastric varices treated by balloon-occluded retrograde transvenous obliteration.

BACKGROUND AND AIM: To assess the short- and long-term outcome of patients with gastric varices (GV) after balloon-occluded retrograde transvenous obliteration (B-RTO) by comparing bleeding cases with prophylactic cases. METHODS: Consecutive 100 patients with GV treated by B-RTO were enrolled in this retrospective cohort study. We compared the technical success, complications, and survival rates between bleeding and prophylactic cases. RESULTS: Of 100 patients, 61 patients were bleeding cases and 39 patients were prophylactic cases. Technical success was achieved in 95% of bleeding case and in 100% of prophylactic case, with no significant difference between these groups (overall technical success rate, 97%). The survival rates at 5 and 10 years were 50% and 22% in bleeding case, and 49% and 36% in prophylactic case, respectively. There was also no significant difference (P = 0.420). By multivariate analysis, survival rates correlated significantly with liver function (hazard ratio 2.371, 95% CI 1.457-3.860, P = 0.001) and hepatocellular carcinoma development (HR 4.782, 95% CI 2.331-9.810, P < 0.001). The aggravating rates of esophageal varices (EV) were 21%, 50%, and 54% at 12, 60, and 120 months after B-RTO. By multivariate analysis, aggravating rates significantly correlated with EV existing before B-RTO (HR 18.114, 95% CI 2.463-133.219, P = 0.004). CONCLUSION: B-RTO for GV could provide the high rate of complete obliteration and favorable long-term prognosis even in bleeding cases as well as prophylactic cases. Management of EV after B-RTO, especially in coexisting case of GV and EV, would be warranted.