Kazufumi Kobayashi

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment

SummaryBackground Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child–Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child–Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand–foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child–Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child–Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Two‐dimensional shear wave elastography with propagation‐based reliability assessment for grading hepatic fibrosis and portal hypertension

The aim of the present study was to examine the diagnostic ability of two‐dimensional shear wave elastography (2D‐SWE) with propagation‐based reliability for grading of hepatic fibrosis and portal hypertension.

Interferon-free treatment for patients with chronic hepatitis C and autoimmune liver disease: higher SVR rates with special precautions for deterioration of autoimmune hepatitis

Background Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR. Three patients took prednisolone (PSL) at baseline, and 3 did not take PSL during interferon-free treatment. In one HCV patient with AIH and cirrhosis, PSL were not administered at baseline, but she needed to take 40 mg/day PSL at week 8 for liver dysfunction. She also complained back pain and was diagnosed with vasospastic angina by coronary angiography at week 11. However, she completed interferon-free treatment. All 5 HCV patients with primary biliary cholangitis (PBC) completed treatment and achieved SVR. Three of these HCV patients with PBC were treated with UDCA during interferon-free treatment. Conclusions Interferon-free regimens could result in higher SVR rates in HCV patients with autoimmune liver diseases. As interferon-free treatment for HCV may have an effect on hepatic immunity and activity of the autoimmune liver diseases, careful attention should be paid to unexpected adverse events in their treatments. Methods Total 12 patients with HCV and autoimmune liver diseases [7 AIH and PBC], who were treated with interferon-free regimens, were retrospectively analyzed.

Presence of non-hypervascular hypointense nodules on Gd-EOB-DTPA enhanced MRI in patients with hepatocellular carcinoma

Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) performed before curative therapy for hepatocellular carcinoma (HCC) can distinguish between intrahepatic distant recurrence and hypervascularization. This study aimed to retrospectively evaluate the presence of non‐hypervascular hypointense nodules on hepatobiliary phase images from Gd‐EOB‐DTPA‐enhanced MRI as a risk factor of the intrahepatic distant recurrence of early stage HCC following radiofrequency ablation (RFA).

Left gastric vein-based noninvasive test for esophageal varices: a same-day comparison of portal hemodynamic assessment with endoscopic appearance

Objective: To examine the effect of hemodynamic assessment of the left gastric vein (LGV) as a noninvasive test to diagnose esophageal varices (EV) in cirrhosis patients. Methods: This cross‐sectional study consisted of 229 cirrhosis patients (62.7 ± 11.8 years; Child‐Pugh score 5–14). One hundred fifty‐four patients had EV (67.2%; small, 53; medium, 71; large, 30). All patients underwent a blood test and Doppler ultrasound followed by upper gastrointestinal endoscopy on the same day. The diagnostic ability for EV was compared between LGV‐related findings and the platelet count/spleen diameter ratio (Plt/Spl). Results: The detectability of the LGV was higher in patients with EV (129/144, 89.6%) than in those without (35/75, 46.7%; p < 0.0001), and was higher in those with large EV (30/30, 100%) than in those without (134/199, 67.3%; p = 0.0002). The positive detection of the LGV showed 100% sensitivity and negative predictive value (NPV) to identify large EV in the whole cohort and compensated group (n = 127). The best cutoff value in the LGV diameter was 5.35 mm to identify large EV, showing 0.753 area under the receiver operating characteristic curve (AUROC) with 90% sensitivity and 96.5% NPV. The Plt/Spl showed 62.1% sensitivity and 87.1% NPV, and the best cutoff value was 442.9 to identify large EV with 0.658 AUROC, which was comparable to LGV‐based assessment (p = 0.162). Conclusions: This same‐day comparison study demonstrated the value of LGV‐based noninvasive test to identify large EV with high sensitivity and NPV in cirrhosis patients at a lower cost.

Histology-Based Assessment of Sonazoid-Enhanced Ultrasonography for the Diagnosis of Liver Metastasis

This retrospective study aimed to assess the diagnostic performance of contrast-enhanced ultrasound with Sonazoid (S-CEUS) for liver metastasis. We enrolled in this study 98 patients with 148 histologically proven liver lesions, with 121 metastases and 27 non-metastases. The S-CEUS technique showed sensitivity in 95.0% (115 of 121), specificity in 44.4% (12 of 27) and accuracy in 85.8% (127 of 148) for the diagnosis of metastasis. Higher body mass index had a negative influence on the positive predictive value and accuracy, and a greater depth of the lesion had a negative influence on the accuracy. The management was changed in 8 patients (8.2%) because of S-CEUS findings. In conclusion, the addition of S-CEUS may offer a great benefit by improvement of the quality of diagnosis and management for patients with cancer who have a tentative diagnosis of liver metastasis by contrast-enhanced computed tomography.

Interrelationship between insulin resistance and portal haemodynamic abnormality in cirrhosis

Background: There are only limited data regarding the effect of impaired portal circulation on the glucose metabolism. The study prospectively examined the interrelationship between insulin resistance (IR) and portal haemodynamic abnormality in cirrhosis. Methods: There were 53 cirrhosis patients (61.6 ± 13.0 years) all presenting gastroesophageal varices. Portal haemodynamics by both hepatic venous catheterisation and Doppler ultrasound were examined with respect to the homeostasis model assessment (HOMA)-IR and HOMA2-IR. The IR was defined by HOMA-IR > 3.0 or HOMA2-IR > 2.0. Results: Forty-two patients (79.2%) had collateral vessels, 38 with left gastric vein, 12 with short/posterior gastric vein, 9 with splenorenal shunt, and 3 with inferior mesenteric vein. Multivariate analysis provided significant factors; wedged hepatic venous pressure (HR1.183, 95% CI 1.012-1.383, p=0.035) for HOMA-IR > 3.0, body mass index for HOMA2-IR > 2.0 (HR1.490, 95% CI 1.176-1.888, p=0.001), and collateral flow volume for both HOMA-IR > 3.0 (HR1.007, 95% CI 1.001-1.014, p=0.015) and HOMA2-IR > 2.0 (HR 1.007, 95% CI 1.002-1.013, p=0.009). The best cut-off value of collateral flow volume was 165 ml/min for detecting the HOMA-IR > 3.0 showing area under the receiver operating characteristic curve (AUROC) 0.688 (Odds ratio, 5.33) with sensitivity 70% and specificity 69.6%, and was 165 ml/min for detecting median value of HOMA2-IR > 2.0 showing AUROC 0.698 (odds ratio, 5.7) with sensitivity 75% and specificity 65.5%. Conclusion: There is a close linkage between the IR and impaired portal haemodynamics presented by the collateral development, suggesting the underlying pathogenesis of portal hypertension in cirrhosis patients.

Well‐tolerated portal hypertension and favorable prognosis in adult patients with extrahepatic portal vein obstruction in Japan

To evaluate the clinical features and prognoses in adult patients with extrahepatic portal vein obstruction (EHO) from the aspect of portal hypertension during the last 20 years in Japan.

Portal response related to shunt occlusion by balloon‐occluded retrograde transvenous obliteration may determine the prognosis of cirrhosis

To determine the prognostic effect of portal hemodynamic responses after balloon‐occluded retrograde transvenous obliteration (B‐RTO) for gastric varices (GV) in cirrhosis patients.

Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events

Background Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen. Case summary Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks. Conclusion Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.