Antiviral Treatment for Hepatitis C Virus Infection after Liver Transplantation

A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary

Hepatocellular Carcinoma: Current Management and Future Development—Improved Outcomes with Surgical Resection

Currently, surgical resection is the treatment strategy offering the best long-term outcomes in patients with hepatocellular carcinoma (HCC). Especially for advanced HCC, surgical resection is the only strategy that is potentially curative, and the indications for surgical resection have expanded concomitantly with the technical advances in hepatectomy. A major problem is the high recurrence rate even after curative resection, especially in the remnant liver. Although repeat hepatectomy may prolong survival, the suitability may be limited due to multiple tumor recurrence or background liver cirrhosis. Multimodality approaches combining other local ablation or systemic therapy may help improve the prognosis. On the other hand, minimally invasive, or laparoscopic, hepatectomy has become popular over the last decade. Although the short-term safety and feasibility has been established, the long-term outcomes have not yet been adequately evaluated. Liver transplantation for HCC is also a possible option. Given the current situation of donor shortage, however, other local treatments should be considered as the first choice as long as liver function is maintained. Non-transplant treatment as a bridge to transplantation also helps in decreasing the risk of tumor progression or death during the waiting period. The optimal timing for transplantation after HCC recurrence remains to be investigated

Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft

Inspiratie boven de Moerdijk? : Een analyse van de territoriale, bestuurlijke, functionele en financiële organisatie van de Nederlandse provincies

Deze bijdrage brengt in kaart welk profiel de Nederlandse provincies hebben en op basis van welke bestuurscultuur hun takenpakket tot stand is gekomen. We belichten vier verschillende dimensies: de territoriale dimensie focust op de plaats van de Nederlandse provincies in het binnenlands bestuur, de bestuurlijke dimensie brengt de rol van interbestuurlijke overlegorganen in kaart, de functionele dimensie schetst de effectieve taken en bevoegdheden van de Nederlandse provincies en de financiële dimensie werpt een blik op de inkomsten en uitgaven en de financiële verhoudingen tussen de besturen

Analysis of the Hepatic Functional Reserve, Portal Hypertension, and Prognosis of Patients With Human Immunodeficiency Virus/Hepatitis C Virus Coinfection Through Contaminated Blood Products in Japan

Background As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. Aim The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. Patients and Methods In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. Results In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/μL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/μL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P <.05). Conclusion These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan

Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors

Background: Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm. Methods: In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed. Results: In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p 2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001). Conclusions: Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm)

Management of Hepatocellular Carcinoma in Japan : JSH Consensus Statements and Recommendations 2021 Update

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC

Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.

OBJECTIVE:This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. DESIGN:Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. RESULTS:Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. CONCLUSION:TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. TRIAL REGISTRATION NUMBER:NCT01217034