Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma.

Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

Primary hepatic angiosarcoma manifesting as hepatic sinusoidal obstruction syndrome: A case report.

BACKGROUND: Primary hepatic angiosarcoma (PHA) is a rare malignancy with a poor prognosis. It is difficult to diagnose PHA because of the lack of specific symptoms or tumour markers, and it rapidly progresses and has a high mortality. To our knowledge, PHA has not been reported to mimic hepatic sinusoidal obstruction syndrome. Herein, we present a case of PHA manifesting as hepatic sinusoidal obstruction syndrome, diagnosed using transjugular liver biopsy, that resulted in the death of the patient. CASE SUMMARY: A 71-year-old man was admitted with the primary complaint of abdominal distension, decreased appetite, fatigue in the previous month, and loss of 10 kg of weight in the past 2 years. Both the liver and spleen were enlarged, and the liver had a medium-hard texture on percussion. Laboratory examinations were performed, and abdominal plain computed tomography (CT) and contrast-enhanced CT showed hepatomegaly and splenomegaly, as well as diffuse low-density shadows distributed in the liver and spleen. Contrast-enhanced CT revealed diffuse, hypodense, nodular or flake shadows in the liver and heterogeneous enhancement in the spleen. A transjugular liver biopsy was performed. Based on the pathology results, the patient was diagnosed with hepatic sinusoidal obstruction syndrome secondary to PHA. The patient's status further deteriorated and he developed serious hepatic failure. The patient was discharged, and died 3 d later. CONCLUSION: PHA is rare and has a poor prognosis; however, transjugular liver biopsy can be safely performed to aid in diagnosis.

A model predicting short-term mortality in patients with advanced liver cirrhosis and concomitant infection.

Infection is a common cause of death in patients with advanced cirrhosis. We aimed to develop a predictive model in Child-Turcotte-Pugh (CTP) class C cirrhotics hospitalized with infection for optimizing treatment and improving outcomes.Clinical information was retrospectively abstracted from 244 patients at Tianjin Third Central Hospital, China (cohort 1). Factors associated with mortality were determined using logistic regression. The model for predicting 90-day mortality was then constructed by decision tree analysis. The model was further validated in 91 patients at Mayo Clinic, Rochester, MN (cohort 2) and 82 patients at Seoul St. Mary's Hospital, Korea (cohort 3). The predictive performance of the model was compared with that of the CTP, model for end-stage liver disease (MELD), MELD-Na, Chronic Liver Failure-Sequential Organ Failure Assessment, and the North American consortium for the Study of End-stage Liver Disease (NACSELD) models.The 3-month mortality was 58%, 58%, and 54% in cohort 1, 2, and 3, respectively. In cohort 1, respiratory failure, renal failure, international normalized ratio, total bilirubin, and neutrophil percentage were determinants of 3-month mortality, with odds ratios of 16.6, 3.3, 2.0, 1.1, and 1.03, respectively (P < .05). These parameters were incorporated into the decision tree model, yielding area under receiver operating characteristic (AUROC) of 0.804. The model had excellent reproducibility in the U.S. (AUROC 0.808) and Korea cohort (AUROC 0.809). The proposed model has the highest AUROC and best Youden index of 0.488 and greatest overall correctness of 75%, compared with other models evaluated.The proposed model reliably predicts survival of advanced cirrhotics with infection in both Asian and U.S.

Tenofovir rescue regimen following prior suboptimal response to entecavir and adefovir combination therapy in chronic hepatitis B patients exposed to multiple treatment failures.

In clinical practice, establishing a subsequent optimum treatment for chronic hepatitis B patients with a history of multiple NAs treatment failures, including a suboptimal response to a final therapy with combined ETV and ADV, is a complicated but crucial challenge. This study investigated the efficacy and safety of a tenofovir rescue regimen in these patients. A total of six eligible patients were enrolled and were switched to a tenofovir rescue regimen. At baseline, the genotypes and genotypic mutations of the reverse transcriptase and surface gene were determined by ultra-deep pyrosequencing, and further clonal analyses of the reverse transcriptase domain were performed to identify multidrug-resistant HBV strains. In addition, HBV DNA levels, serology, and biochemistry parameters were monitored at baseline and every 3 months, and abdominal ultrasonography was performed at baseline and every 6 months. All patients were confirmed to harbor LAM-related resistant HBV strains. After switching to the tenofovir rescue treatment, all patients had an undetectable level of HBV DNA within 6 months and achieved normalization of the ALT level within 9 months. These virological and biochemical responses persisted until the end of the observation period. None of the patients developed clinical deterioration or any adverse events related to the tenofovir therapy during the median 16.5-month follow-up. In conclusion, the tenofovir rescue regimen can be employed confidently as a highly effective and safe treatment choice following a suboptimal response to ETV plus ADV therapy for a subset of chronic hepatitis B patients with a history of multiple unsuccessful antiviral treatments.

Comparison of the effects of the pretreatment and treatment with RhIL-11 on acute liver failure induced by D-galactosamine.

OBJECTIVE: To compare the effects of the pretreatment and treatment with recombinant human interleukin-11 (rhIL-11) on acute liver failure induced by D-galactosamine (D-GalN). METHODS: The Sprague Dawley (SD) male rats were randomly divided into five groups: control, model, pretreatment, treatment and repeated treatment groups. The acute liver failure model was established by intraperitoneal injections with D-GalN (1400 mg/kg). The pretreatment, treatment and repeated treatment groups were injected subcutaneously with rhIL-11 (500 µg/kg). The rats were killed 24, 48, or 72 h after the D-GalN injection. The symptoms and survival rate of the rats were analysed. Liver injury was assessed by serum ALT and AST levels and by histological analysis. The percentage of Proliferating Cell Nuclear Antigen (PCNA+) cells in the liver tissue was evaluated by immunohistochemistry. RESULTS: Compared with the model group, the survival rate of the pretreatment group improved markedly, and these rats were protected from severe hepatic injury, as shown by the decreased serum ALT and AST levels and improved histological results. In the pretreatment group, the percentage of PCNA+ cells was significantly increased in the late stage. In contrast, the treatment and repeated treatment groups did not show improved survival rates or the prevention of severe hepatic injury, as shown by the absence of any decrease in the serum ALT and AST levels and the lack of any improvement in the histological results.The treatment and repeated treatment groups also have a significant increase in the percentage of PCNA+ cells in the late stage. CONCLUSIONS: The pretreatment with rhIL-11 can reduce acute liver failure and protect the liver. In contrast, the treatment with rhIL-11 cannot reduce acute liver failure or protect the liver.

[Polymorphisms of inhibin α gene exon 1 in buffalo (Bubalus bubalis), gayal (Bos frontalis) and yak (Bos grunniens)].

To elucidate the genetic characteristics of the bovine Inhibin α subunit (INHA) gene, the polymorphisms in exon 1 of INHA and its bilateral sequences were assayed using PCR with direct sequencing in buffalo, gayal and yak. A comparative analysis was conducted by pooled the results in this study with the published data of INHA on some mammals including some bovine species together. A synonymous substitution c.73C>A was identified in exon 1 of INHA for buffalo, which results in identical encoding product in river and swamp buffalo. In gayal, two non-synonymous but same property substitutions in exon 1 of INHA, viz. c.62 C>T and c.187 G>A, were detected, which lead to p. P21L, p. V63M changes in INHA, respectively. In yak, nucleotide substitution c.62C> T, c.129A>G were found in exon 1 of INHA, the former still causes p. P21L substitution and the latter is synonymous. For the sequence of the 5'-flanking region of INHA examined, no SNPs were found within the species, but a substitution, c. -6T>G, was found. The nucleotide in this site in gayal, yak and cattle was c. -6G, whereas in buffalo it was c. -6T. Meanwhile, a 6-bp deletion, namely c. 262+31_262+36delTCTGAC, was found in the intron of buffalo INHA gene. For this deletion, wild types (+/+) account for main part in river buffalo while mutant types (-/-) are predominant in swamp buffalo. This deletion was not found in gayal, yak and cattle, though these all have another deletion in the intron of INHA, c. 262+78_262+79delTG. The results of sequence alignment showed that the substitutions c. 43A and c. 67G in exon 1 of INHA are specific to buffalo, whereas the substitutions c. 173A and c. 255G are exclusive to gayal, yak and cattle, and c. 24C, c. 47G, c. 174T and c. 206T are specific to goat. Furthermore, there are few differences among gayal, yak and cattle, but there relatively great differences between buffalo, goat and other bovine species regarding the sequences of INHA exon 1.