Aim
Few studies have reported the efficacy and safety of ramucirumab (RAM) after atezolizumab plus bevacizumab (Atezo/Beva) treatment and the overall associated outcomes. Thus, we aimed to evaluate ...the therapeutic effects and safety of RAM post‐treatment with Atezo/Beva.
Methods
This retrospective study enrolled 46 patients with unresectable hepatocellular carcinoma who were treated with RAM. The patients were classified into the RAM administered following Atezo/Beva failure (n = 12) or RAM administered following other drug failure (n = 34) groups. Progression‐free survival (PFS), overall survival (OS), and adverse event (AE) rates were assessed.
Results
There were significant differences in the objective response rates and disease control rates between the RAM administered following Atezo/Beva and RAM administered following others groups (objective response rate 33.3%. vs. 0.0%, p = 0.001; disease control rate 83.3% vs. 32.3, p = 0.001). Although there was no significant difference in the OS rates, the median PFS rates in the RAM administered following Atezo/Beva group was significantly higher than in the RAM administered following others group (PFS 3.9 months. vs. 1.9 months, p = 0.047). The AE rates were comparable between the two groups; ascites was the most common AE (45.6%). Using decision tree analysis, the presence of splenomegaly and body mass index (BMI) < 19.8 were the first and second splitting variables for RAM‐related ascites, respectively.
Conclusions
The therapeutic effect of RAM increased in patients with Atezo/Beva failure. Patients with splenomegaly and low BMI should be monitored for ascites during RAM treatment.
The therapeutic effect was significantly higher in the ramucirumab (RAM) following atezolizumab plus bevacizumab (Atezo/Beva) group than in the RAM following treatment other than Atezo/Beva group. The development of ramucirumab‐related ascites was associated with splenomegaly and low body mass index.
Aim
Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging ...method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion.
Methods
Shear wave elastography and contrast‐enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4)‐induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples.
Results
Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C‐peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC.
Conclusions
In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.
The aim of this study was to prospectively measure liver stiffness with real‐time tissue elastography in patients with nonalcoholic fatty liver diseases (NAFLD) and to compare the result with the ...clinical assessment of fibrosis using histological stage. One hundred and eighty‐one prospectively enrolled patients underwent real‐time tissue elastography, with the first 106 being analyzed as the training set and the remaining 75 being evaluated as the validation set. Hepatic and splenic elastic ratios were calculated and compared with stage of histological fibrosis. Portal hypertension (PH) was assessed. Real‐time tissue elastography cut‐off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using these cut‐off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%‐96.0% in all stages. Only portal fibrosis correlated with the hepatic elastic ratio by multivariate analysis. The area under the receiver operating characteristic curve of elastic ratio better correlated than serum fibrosis markers in both early and advanced fibrosis stages. Patients with PH, defined by splenic elasticity, had early fibrosis. Patients with severe PH were found only in the group with cirrhosis. Conclusion: Real‐time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD. (HEPATOLOGY 2012)
Aim
The predictors for the development of hepatocellular carcinoma (HCC) after direct‐acting antiviral (DAA) treatment were investigated.
Methods
A total of 1174 patients with chronic hepatitis C ...virus infection were treated with DAA therapy (sofosbuvir and ledipasvir n = 615, sofosbuvir and ribavirin n = 380, and daclatasvir and asunaprevir n = 179) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed.
Results
During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre‐ and post‐treatment factors identified the Fibrosis‐4 (FIB‐4) index (hazard ratio HR = 1.09; 95% confidence interval CI, 1.021–1.178; P = 0.011) and post‐treatment α‐fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054–1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high‐score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1‐ and 2‐year cumulative incidence rates of HCC were 6.1% and 14.4%.
Conclusions
A high FIB‐4 index and a high post‐treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.
Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the ...characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as 'early recurrence', and recurrence more than 1 year after as 'late recurrence'. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment alpha-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026-1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96-0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases. Keywords: DAA, Time of recurrence, Renal function, Treatment history, Risk factor, Prediction, Follow-up, HCV, Sex, Male, SVR, Number of treatments, Diabetes mellitus
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with d-penicillamine 9 years prior. ...Hepatocellular carcinoma had been diagnosed at 36 years old and treated with radiofrequency ablation therapy. One year later, renal cancer and recurrent hepatocellular carcinoma had developed. The hepatocellular carcinoma was treated after renal cancer surgical resection of a clear-cell-type renal cell carcinoma, with iron, rather than copper, deposited on the renal cancer cells. This patient harbored a novel mutation, p. Leu1395Terfs in ATP7B.
The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a ...scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.
Aim
Patients often do not respond truthfully to physicians' interviews concerning alcohol. Few reports regarding the level of alcohol dependence in patients with chronic liver disease (CLD) have been ...presented. This study aimed to elucidate severity distribution in patients with CLD using the alcohol use disorders identification test (AUDIT).
Methods
From March to June 2022, 2034 Japanese outpatients with CLD, including 415 cases associated with hepatitis C virus, 436 with hepatitis B virus, 173 with alcohol‐related liver disease (ARLD), and 1010 with other factors, were interviewed using AUDIT. Clinical features related to alcohol use in these patients were then retrospectively evaluated.
Results
In all patients, an AUDIT score 8–14 (harmful use) was noted in 5.8% of hepatitis C virus, 8.9% of hepatitis B virus, 24.3% of ARLD, and 4.4% of other groups, respectively (P < 0.001), while a score ≥15 (dependency) was noted in 3.4%, 3.0%, 27.7%, and 1.9%, respectively (P < 0.001). When the country was divided into regions, the percentages remained similar. Comparisons between patients with and without an AUDIT score ≥8 (n = 1412), performed after exclusion of those without related data (n = 622), showed no significant differences for hepatic reserve function, while those with harmful alcohol use were significantly younger (66 vs. 70 years, P = 0.006) and had a larger percentage of men (80.4% vs. 45.1%, P < 0.001).
Conclusion
Harmful alcohol and alcohol dependency were observed in approximately 10% of patients with viral or non‐viral CLD, after excluding patients with ARLD. Assessment of alcohol intake by use of the AUDIT questionnaire as well as adequate intervention should be considered necessary.
Aim
Lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Metabolic dysfunction‐associated fatty liver disease (MAFLD) is becoming a major etiology of HCC. We aimed to evaluate the ...impact of MAFLD on the efficacy of lenvatinib.
Methods
We enrolled 320 patients with HCC who were treated with lenvatinib. All patients were classified into the MAFLD (n = 155) and non‐MAFLD (n = 165) groups. Independent factors for overall survival (OS) were analyzed. In the stratification analysis, HCC was categorized as non‐viral (n = 115) or viral HCC (n = 205).
Results
The OS rate was significantly higher in the MAFLD group than in the non‐MAFLD group (median 21.1 vs. 15.1 months, p = 0.002). Multivariate analysis demonstrated that, in addition to albumin‐bilirubin grade and Barcelona Clinic Liver Cancer stage, MAFLD was identified as an independent factor for OS (HR 0.722, 95% CI 0.539–0.966, p = 0.028). In the stratification analysis, the OS rate was significantly higher in the MAFLD group than in the non‐MAFLD group among patients with non‐viral HCC (median 21.1 vs. 15.1 months, p = 0.002), but not in patients with viral HCC. Furthermore, MAFLD was an independent negative risk factor for OS in patients with non‐viral HCC (HR 0.506, 95% CI 0.297–0.864, P < 0.01). However, MAFLD was not an independent factor for OS in patients with viral HCC.
Conclusions
MAFLD was a beneficial factor for survival in patients with HCC treated with lenvatinib. Moreover, the better OS of the MAFLD group was more pronounced in patients with non‐viral HCC. Lenvatinib may be a suitable agent for patients with non‐viral HCC and MAFLD.
Metabolic dysfunction‐associated fatty liver disease (MAFLD) was an independent predictive factor for improved overall survival in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. The overall survival of patients with HCC was significantly higher in the MAFLD group than in the non‐MAFLD group. By the treatment with lenvatinib, a higher overall survival in the MAFLD group was observed in patients with non‐viral HCC, but not in patients with viral HCC.
Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis ...remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009–2013, n = 86; period 2: 2014–2018, n = 132; period 3: 2019–2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1–3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin–bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.
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