Sorafenib (S) for hepatocellular carcinoma (HCC) treatment: Russian experience in cirrhotic (C) and non-cirrhotic (non-C) patients.

e14723 Background: S is the standard for HCC treatment in advanced stage. There is no date about an etiology of HCC and S efficacy/toxicity in Russian pts. Methods: 69 patients (19 f/ 50 m, average age 54 years) with advanced HCC BCLC A/B/C/D 1/30/38/0 were treated with sorafenib as a I-st line. S treatment: 400 mg bid until progression, uncontrolled toxicity, or death. S dose reduced when toxicity (NCI CTC, ver 3.0) ≥Gr 2 occured. We evaluate influences of BCLC and Child-Pugh stage, presence of C and/or viral hepatitis on S efficacy and toxicity. Results: 33 (48%) out of 69 patients had C and 36 (52%) were non-C. No hepatitis - 36 pts (C/non-C - 5/31 pts), 16 pts had HBV (C/non-C – 15/1), 17 pts had HCV (C/non-C – 15/2), 1 pt had hepatitis B+/C without C. Clinically significant toxicity (Gr 2/3) occurred in 20 (C/non-C – 9/12) pts: HFS 1/6, skin rash 3/3, diarrhea 3/2, arterial hypertension (AG) 2/0, asthenia 1/1, fever 1/0. S interrupted in 12 (C/non-C – 5/7) pts: HFS- 0/4, skin rash -1/3 diarrhea - 2/1 and AG - 2/0. Efficacy evaluated in 68 pts: PR - 5 (7,4%) pts, stable – 46 (67,6%) and disease progressed in 17 (25%) pts. All PR (OR=13,9%) observed in non-C pts: 6, 9,3, 10, 10,2 and 13+ mo). Median PFS and OS on S treatment was 5,4 and 9,3 mo respectively. No significant difference were in PFS and OS for C and non-C pts, irrespectively for HCV/HBV status and Child-Pugh stage A/B (Table). Conclusions: More than 50% of HCC pts in Russia are non-C and don’t have HBV/HCV. Clinically significant toxicity of S differs in C/non-C pts, with prevalence of skin side effects in non-C pts, AG and diarrhea in C group. Non-C HCC pts have better chance to respond to S treatment. However we didn’t find any significant difference of S treatment in terms of survival and side effects between C and non-C pts. [Table: see text]

Download Full-text

Relationship between platelet count and hepatic failure and residual liver regeneration after hemihepatectomy in patients with hepatitis B-related primary hepatocellular carcinoma

10.21203/rs.2.16653/v1 ◽

2019 ◽

Author(s):

Chuhui Ye ◽

Banghao Xu ◽

Kaiyi Lu ◽

Tingting Lu ◽

Ling Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Hepatitis B ◽

Liver Failure ◽

Liver Regeneration ◽

Liver Volume ◽

Primary Hepatocellular Carcinoma ◽

Postoperative Liver Failure ◽

Regeneration Rate ◽

Significant Difference

Abstract Objective A retrospective analysis of the influences of platelet (PLT) counts on liver failure and liver regeneration in patients with primary hepatocellular carcinoma (HCC) provides a treatment strategy for clinical prevention and treatment of postoperative liver failure and residual liver regeneration. Method The clinical data of 111 patients with a background of hepatitis B virus infection and who underwent (expanded) half liver resection at the First Affiliated Hospital of Guangxi Medical University from June 2012 to June 2017 were collected and statistically analyzed. Results　On the basis of the International Study Group of Liver Surgery liver failure-grading standards and Dino–Clavien postoperative complication criteria, the incidence of grade B and above liver failure was 55%, and complication II level and above was 47.5% in the PLT decline group after semihepatectomy. The incidence rates in the normal group were 26.8% and 23.9%. A statistically significant difference was determined in the two groups (P1=0.003, P2 = 0.011). The average volumes of liver hyperplasia (residual liver volume (RLV)80.4 days − RLV) in the PLT decline and normal groups were 132.09 ± 61.89 cm3 and 190.89 ± 91.98c cm3, respectively; the average rates of hyperplasia ((RLV80.4days−RLV)/RLV) were 16.59%± 7.36% and 24.78% ± 10.82%. The difference between the two groups was statistically significant (PProliferation = 0.001, PProliferation rate = 0.001). Univariable and multivariable logistic regression analyses of postoperative liver failure grade and proliferation rate in patients who underwent semihepatectomy suggested that the decrease in postoperative PLT count (PLT < 125 × 109/L) might be an independent risk factor of severe posthepatectomy liver failure (PHLF) (PHLF-B or above) and residual liver regeneration rate for patients with primary HCC after half liver resection. No death occurred. Conclusions A correlation existed between PLT count and postoperative PHLF or liver regeneration. Monitoring PLT counts after liver resection may help us predict the suffering from PHLF-B or above and severe postoperative complications.

Download Full-text

Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus

Cancer Control ◽

10.1177/10732748211039758 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110397

Author(s):

Hae Lim Lee ◽

Si Hyun Bae ◽

Jaejun Lee ◽

Pil Soo Sung ◽

Sung Won Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B ◽

Liver Function ◽

Clinical Characteristics ◽

Endemic Area ◽

Metabolic Disorders ◽

Advanced Tumor Stage ◽

Advanced Tumor ◽

Significant Difference ◽

The Impact

Background and Aims This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. Methods A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. Results The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002–2011 to 12% in 2012–2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III–V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. Conclusion Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.

Download Full-text

The use of Ingaron® in the treatment of chronic viral hepatitis B

Aspirantskiy Vestnik Povolzhiya ◽

10.17816/2072-2354.2020.20.3.63-67 ◽

2020 ◽

Vol 20 (5-6) ◽

pp. 63-67

Author(s):

Ekaterina A. Zaytseva ◽

Larisa L. Popova ◽

Dmitry Yu. Konstantinov

Keyword(s):

Side Effects ◽

Hepatitis B ◽

Viral Hepatitis ◽

Antiviral Therapy ◽

Treatment Regimen ◽

Chronic Viral Hepatitis ◽

Immunomodulating Therapy ◽

Number Of Patients ◽

Viral Hepatitis B ◽

Clinically Significant

The possibility of antiviral therapy with the direct antiviral drugs Entecavir and Ingaron, as an antiviral and immunomodulating therapy, was studied in patients with the recurrent chronic viral hepatitis B. The study showed the applicability of this treatment regimen, due to the increase in the number of patients with SVR, high tolerability and the absence of clinically significant side effects.

Download Full-text

Evolution of Survival Impact of Molecular Target Agents in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000519868 ◽

2021 ◽

pp. 1-13

Author(s):

Kazufumi Kobayashi ◽

Sadahisa Ogasawara ◽

Aya Takahashi ◽

Yuya Seko ◽

Hidemi Unozawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Duration ◽

Molecular Target ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Stage ◽

First Line ◽

Advanced Hcc ◽

Period 2 ◽

Study Population ◽

The Impact

Background and Aims: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet. Approach and Results: We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, p < 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively (p = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; p < 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC. Conclusions: The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.

Download Full-text

Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920937422 ◽

2020 ◽

Vol 12 ◽

pp. 175883592093742

Author(s):

Yingqiang Zhang ◽

Guihua Huang ◽

Hongfei Miao ◽

Ze Song ◽

Xiaoying Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Supportive Care ◽

Liver Tumor ◽

Survival Outcomes ◽

Primary Resistance ◽

Advanced Hcc ◽

B Virus ◽

Tumor Load

Aims: This study aimed to (a) assess the effectiveness and safety of apatinib as a subsequent treatment for patients with sorafenib-resistant hepatocellular carcinoma (HCC), and (b) identify the clinical factors influencing their treatment outcomes. Methods: The electronic medical records of consecutive patients with newly diagnosed advanced HCC treated with first-line sorafenib from 2015 to 2017 were retrospectively reviewed. Patients who were confirmed to have primary resistance to sorafenib were enrolled in this study. The outcomes of patients treated with apatinib were compared with those of patients who received supportive care. The primary endpoint was overall survival (OS). Results: A total of 92 patients with sorafenib-resistant advanced HCC (84 men and 8 women; mean age, 51.9 years) were included. All patients had an etiology of hepatitis B. The median OS in the overall cohort was 5.0 months [95% confidence interval (CI): 3.9, 6.0]. Of 92 patients, 58 (63.0%) were treated with apatinib, and 34 (37.0%) received supportive care. Apatinib treatment was associated with longer survival times than supportive care for patients with sorafenib-resistant advanced HCC (median OS: 7.0 versus 4.0 months, p < 0.001). The results of the multivariate analysis demonstrated that liver tumor load [hazard ratio (HR): 3.653, 95% CI: 2.047, 5.965, p < 0.001] and extrahepatic spread (HR: 0.303, 95% CI: 0.231, 0.778, p = 0.003) were independent predictors of OS after apatinib treatment. Conclusion: This study showed that subsequent apatinib treatment may improve survival outcomes compared with supportive care for patients with sorafenib-resistant, advanced hepatitis B virus (HBV)-related HCC, especially for patients who have a lower liver tumor load and extrahepatic spread.

Download Full-text

Endobronchial metastases from hepatocellular carcinoma: a case report

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492319876493 ◽

2019 ◽

Vol 27 (8) ◽

pp. 703-706 ◽

Cited By ~ 1

Author(s):

Francis Park-yun Cheung ◽

Prudence Anne Russell ◽

Naveed Zeb Alam ◽

Gavin Michael Wright

Keyword(s):

Hepatocellular Carcinoma ◽

Case Report ◽

Airway Obstruction ◽

Palliative Treatment ◽

Advanced Stage ◽

Rare Occurrence ◽

Diagnosis And Management ◽

Clinically Significant ◽

Symptom Palliation ◽

Prompt Diagnosis

Advanced-stage hepatocellular carcinoma presenting with endobronchial metastases is an extremely rare phenomenon, with only a few cases reported to date. Despite endobronchial metastases being a rare occurrence, the clinically significant sequelae require prompt diagnosis and management. Therapeutic bronchoscopy represents an effective palliative treatment for malignant airway obstruction. This case report describes a 62-year-old man who presented with bilateral endobronchial metastases from advanced-stage hepatocellular carcinoma, requiring symptom palliation with laser bronchoscopy.

Download Full-text

Cabozantinib in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16668 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16668-e16668

Author(s):

Fabian Finkelmeier ◽

Bernhard Scheiner ◽

Catherine Leyh ◽

Jan Best ◽

Thorben Wilhelm Fründt ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Disease ◽

Side Effects ◽

Real World ◽

Advanced Hepatocellular Carcinoma ◽

Duration Of Treatment ◽

Advanced Liver Disease ◽

Advanced Hcc ◽

International Multicenter

e16668 Background: The multikinase inhibitor cabozantinib has been approved by the European Medicines Agency in November 2018 for hepatocellular carcinoma (HCC) prior treated with sorafenib. We report, to our knowledge, for the first time safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 10 centers in Austria and Germany. Patients´ characteristics, side effects, duration of treatment and survival data were analyzed until January 17, 2020. Results: 74 patients were identified of whom 65 patients were male (88%) and 9 were female (12%). The median age at the start of cabozantinib treatment was 66 years. The most common underlying liver diseases included hepatitis C in 15 (20%), hepatitis B in 6 (8%), alcohol in 17 (23%) and NAFLD/NASH in 20 (27%) patients, respectively. 64 patients (86%) had BCLC stage C and 43 patients (58%) were Child Pugh A. Cabozantinib was used as systemic second- and third-line treatment in 37 (50%), and 25 (34%) patients, respectively. In the remaining patients cabozantinib was used in further lines. The median starting dose was 40 mg (20-60 mg). In 26 patients (35%) a dose reduction due to side effects was performed. Following best responses under cabozantinib were documented: partial response in 4 (5%), stable disease in 22 (30%), and progressive disease in 24 (32%) patients, respectively. 24 patients (32%) had not yet been evaluable. The median duration of cabozantinib treatment was 4.4 months. 35 patients (47%) had died at day of data analysis. The median overall survival from start of cabozantinib treatment was 7.7 months. Most common adverse events were fatigue and diarrhea. Conclusions: Cabozantinib treatment was effective, safe and feasible in patients with advanced HCC. Patients in the real life setting had more advanced liver disease – only 58% of patients were Child A. Duration of treatment was similar to the phase 3 trial (CELESTIAL). However, overall survival was shorter, probably due to more advanced liver disease.

Download Full-text

Quantification of Pregenomic RNA and Covalently Closed Circular DNA in Hepatitis B Virus-Related Hepatocellular Carcinoma

International Journal of Hepatology ◽

10.1155/2013/849290 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Fugui Bai ◽

Yoshihiko Yano ◽

Takumi Fukumoto ◽

Atsushi Takebe ◽

Motofumi Tanaka ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Circular Dna ◽

Expression Levels ◽

Covalently Closed Circular Dna ◽

Occult Hbv ◽

Significant Difference ◽

B Virus ◽

Liver Tissues

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P<0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

Download Full-text

Enhanced antitumour effect for hepatocellular carcinoma in the advanced stage using a cyclodextrin-sorafenib-chaperoned inclusion complex

Biomaterials Science ◽

10.1039/c9bm01190k ◽

2019 ◽

Vol 7 (11) ◽

pp. 4758-4768

Author(s):

Chiuyen Phan ◽

Ziyang Zheng ◽

Jianwei Wang ◽

Qiwen Wang ◽

Xiurong Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Inclusion Complex ◽

Inclusion Complexes ◽

Nude Mice ◽

Advanced Stage ◽

Antitumour Effect ◽

Advanced Hcc ◽

Tumor Bearing

We have proposed and classified the HCC tumor of HCC tumor-bearing BALB/c nude mice to four stages. Cyclodextrin-sorafenib-chaperoned inclusion complexes were prepared and applied to treat advanced HCC tumor-bearing mice.

Download Full-text

Epidemiological Characteristics of Advanced Hepatocellular Carcinoma in the Northern Region of Vietnam

Cancer Control ◽

10.1177/1073274819862793 ◽

2019 ◽

Vol 26 (1) ◽

pp. 107327481986279 ◽

Cited By ~ 2

Author(s):

Van Quang Le ◽

Van Hieu Nguyen ◽

Van Hung Nguyen ◽

Thanh Long Nguyen ◽

Staci L. Sudenga ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hcv Infection ◽

High Rate ◽

Advanced Hepatocellular Carcinoma ◽

Female Ratio ◽

Advanced Hcc ◽

Significant Difference ◽

Epidemiological Characteristics

Epidemiological characteristics of hepatocellular carcinoma (HCC) in Southern Vietnam has been well reported as in Globocan 2018 while data from the North has still not been fully presented. Therefore, we conducted this retrospective descriptive study on 198 advanced HCC patients treated at 3 major hospitals in Northern Vietnam to describe demographic features, HCC risk factors, and correlation among them in patients with advanced HCC. This information will lead to prevention efforts and provide information for allocating funds for treatment. The median age at diagnosis was 57 years (range: 19-86) and the male/female ratio was 8.9/1. The proportions of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were 81.3% and 5.6%, respectively. Hepatitis C virus infection rate was significantly higher in patients <50 years old (12.5% vs 3.3%, P = .016). There was no significant difference in age or viral hepatitis infection status by gender. Only 7.6% of patients diagnosed with advanced HCC were asymptomatic. In conclusion, with the high rate of HBV infection among patients with advanced HCC, it is necessary for increasing prevention efforts in HBV screening. Furthermore, HCV infection should be noticed in patients with advanced HCC younger than 50 years old.

Download Full-text