Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis,End-Stage Renal Disease and Transplant Medicine

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.     

Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence

Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.     

肝细胞移植治疗肝硬化的疗效

目的建立SD大鼠药物性肝硬化模型,探讨原代肝细胞移植治疗大鼠肝硬化的疗效。方法经四氯化碳(Carbon tetrachloride,CCL4)诱导大鼠肝硬化模型,将40只模型大鼠分为2组,每组20只,Ⅰ组经脾尾注射约2×107个肝细胞,Ⅱ组经脾尾注射0.4 ml Hank’s液。观察每组大鼠的存活情况及肝功能变化;HE染色观察脾脏病理变化;免疫荧光观察植入的肝细胞在大鼠脾内合成白蛋白(Serum albumin level,ALB)的功能。结果经CCL4诱导10周后,大鼠肝脏经HE染色发现假小叶形成,表明成功建立了肝硬化模型;移植术后8周,Ⅰ组大鼠存活率(75%)显著高于Ⅱ组(35%),差异有统计学意义(P<0.01);Ⅰ组大鼠的血清ALB水平较Ⅱ组明显升高(P<0.05),血氨(Serum ammonia level,AMM)水平较Ⅱ组明显降低(P<0.05);Ⅰ组大鼠移植术后1、8周,大量肝细胞在脾脏红髓中定植下来;Ⅰ组大鼠移植术后5周,植入的肝细胞在大鼠脾内具有合成白蛋白的功能。结论 CCL4能稳定诱导肝硬化动物模型;同种异体肝细胞移植能提高肝硬化大鼠的生存率,并改善肝性脑病和低蛋白血症。     

解剖性肝切除在肝硬化肝癌手术中的临床应用

目的探讨解剖性肝切除在肝硬化肝癌手术中的效果。方法回顾分析36例肝硬化肝癌患者行解剖性肝切除术的临床资料。结果 36例患者手术均获得成功,手术时间80～210min,出血量100～1200mL。无术中死亡,无肝功能衰竭等严重并发症。结论解剖性肝切除是治疗肝硬化肝癌一种安全有效的手术方式。     

Characterization and control of foulants occurring from RO disc-tube-type, membrane treating, fluorine manufacturing, process wastewater

This study was carried out to find a way to limit fouling of disc-tube-type reverse osmosis membranes in the treatment of acid rinse wastewater from the fluorine manufacturing process as well as to pretreat the wastewater before it entered the membrane process. Experiments showed that the scale consisted of Ca²⁺, SO₄⁻² and F⁻. Complex scales were removed in a subsequent procedure where the membrane was rinsed with NaOH followed by citric acid which could consequently recover its flux up to 86%. Cleaning chemicals had to be used regularly for efficient recovery of permeate flux. Ultrasonic cleaning could also improve the recovery of permeate flux up to 83%. Calcium salts were used to remove fluoride ions. CaCl₂ removed fluoride ions up to 11% more than Ca(OH)₂ at 0.5 [Ca²⁺]/[F⁻]. At acidic pH 4-7 or alkaline pH 7 and above, residual fluoride ions increased as Ca²⁺ reacted more efficiently with Cl⁻, OH⁻ and SO₄⁻² rather than F⁻. On the other hand, fluoride ions were best removed at pH 7. Adding Ca²⁺ salt above pH 7 caused an increase of residual Ca²⁺ salt in the effluent, even if fluoride ions can be ideally removed in the form of CaF₂ at a pH over 11.     

Hypoxic and highly angiogenic non-tumor tissues surrounding hepatocellular carcinoma: the 'niche' of endothelial progenitor cells

Our previous investigations showed that mobilized endothelial progenitor cells (EPCs) are enriched in non-tumor tissues (NT) surrounding hepatocellular carcinoma (HCC), compared to in tumor tissues (TT). This particular recruitment of EPCs is worth investigating further. The mobilization, recruitment, homing, and incorporation of EPCs into tumors require the participation of multiple factors, including angiogenic factors, adherent molecules, endothelial cells, hypoxic environment, etc. Therefore, we hypothesized that NT might be a hypoxic and highly angiogenic area, into which many more EPCs are recruited and homed. In the last three years, we evaluated the hypoxic condition, angiogenic factors and angiogenic index using frozen tissues or tissue microarrays from 105 patients who had undergone hepatectomy for HCC, and here we review our results and the studies of others. All results showed the expression of Hypoxiainducible factor-1α was higher in NT than in TT. The expression of VEGFA, bFGF, TGF-β, MCP-1, MMP-9, TIMP-2, and endostatin in NT was significantly higher than in normal liver and TT. Meanwhile, the expression of CD105-the surface marker of activated endothelial cells-was also higher in NT than in TT at the protein and mRNA levels. These investigations showed that NT is a hypoxic and highly angiogenic area, which may be the 'niche' of EPCs. The particular background in HCC may be related to liver cirrhosis. Therefore, non-tumor tissues surrounding HCC may be the 'niche' of endothelial progenitor cells.     

Hepatitis B Virus Infection,MicroRNAs and Liver Disease

Hepatitis B virus (HBV) attacks the liver and can cause both acute as well as chronic liver diseases which might lead to liver cirrhosis and hepatocellular carcinoma. Regardless of the availability of a vaccine and numerous treatment options, HBV is a major cause of morbidity and mortality across the world. Recently, microRNAs (miRNAs) have emerged as important modulators of gene function. Studies on the role of miRNA in the regulation of hepatitis B virus gene expression have been the focus of modern antiviral research. miRNAs can regulate viral replication and pathogenesis in a number of different ways, which includefacilitation, direct or indirect inhibition, activation of immune response, epigenetic modulation, etc. Nevertheless, these mechanisms can appropriately be used with a diagnosticand/or therapeutic approach. The present review is an attempt to classify specific miRNAs that are reported to be associated with various aspects of hepatitis B biology, in order to precisely present the participation of individual miRNAs in multiple aspects relating to HBV.