The association of hepatitis C infection with the onset of CKD and progression into ESRD

Hepatitis C virus (HCV) infection is not only an important cause of chronic liver disease, but extrahepatic manifestations are common and include chronic kidney disease (CKD). HCV is classically associated with cryoglobulinemic glomerulonephritis in the context of mixed cryoglobulinemia syndrome, but other glomerular diseases also occur and may be significantly under‐recognized. HCV may cause glomerular disease by immune complex deposition; however, other potential mechanisms by which HCV promotes CKD include a direct cytopathic effect of the virus on renal tissue, and by its association with accelerated atherosclerosis, insulin resistance, and chronic inflammation. Epidemiologic studies show HCV infection confers an increased risk of incident CKD and accelerates progression of CKD to end‐stage renal disease (ESRD) in the general population, as well as subpopulations including diabetic patients, those coinfected with human immunodeficiency virus (HIV), and kidney transplant recipients. Patients with CKD and HCV infection experience inferior clinical outcomes, including poorer quality of life and an increased risk of mortality. Treatment with interferon‐based regimens is associated with decreased risk of incident CKD and ESRD, though prior studies are limited by the small number of patients with HCV and CKD who underwent treatment. With the advent of new, well‐tolerated direct‐acting antiviral combinations that are not cleared by the kidneys, it is possible to treat all genotypes of HCV infection in patients with CKD and ESRD. More data on the effect of direct‐acting antivirals on CKD incidence and progression are necessary. However, there is every expectation that with improved access to HCV treatment, the burden of CKD in patients with HCV could significantly decline.     

Rheumatologic manifestations of chronic hepatitis C infection

The many rheumatologic manifestations associated with chronic hepatitis C virus (HCV) infection include arthralgia, myalgia, arthritis, vasculitis, and sicca syndrome. Arthralgia is the most common extrahepatic manifestation and may indicate mixed cryoglobulinemia or an adverse reaction to interferon therapy. HCV arthritis unrelated to cryoglobulinemia is far less common but constitutes an independent entity. The picture may mimic rheumatoid arthritis (RA), particularly as rheumatoid factor is present in 50-80% of cases. Tests are usually negative for antibodies to cyclic citrullinated peptides (anti-CCP), which may help to differentiate the two conditions. The management of HCV arthritis is empirical and poorly standardized. Although low-dose glucocorticoid therapy, hydroxychloroquine, and methotrexate have been used successfully in several patients, little is known about their hepatic safety profile. Arthritis associated with cryoglobulinemia usually responds to antiviral treatment. Sicca syndrome is common in patients with chronic HCV infection and shares similarities with primary Sj?gren syndrome, suggesting that HCV infection may deserve to be included among the causes of secondary Sj?gren syndrome. HCV-associated vasculitis is usually related to cryoglobulinemia, although a few cases of polyarteritis nodosa-like disease affecting the medium-sized vessels have been reported. Other conditions reported in patients with chronic HCV infection include fibromyalgia, systemic lupus erythematosus (SLE), antiphospholipid syndrome, and osteosclerosis.     

Treating hepatitis C virus in dialysis patients: How,when, and why?

The identification of hepatitis C virus (HCV) occurred in 1989, and soon thereafter, it was recognized that there was a higher prevalence of anti‐HCV seropositivity in patients with end‐stage renal disease (ESRD) when compared to the general population. Multiple extrahepatic manifestations have been associated with HCV infection in patients with ESRD; these include an increased prevalence and risk of cardiovascular complications, insulin resistance, diabetes mellitus, and lymphoproliferative disorders. Infection with HCV has also been associated with an increased relative risk of mortality in the ESRD patient when contrasted to those patients without infection. The availability of second‐generation direct‐acting antiviral agents has revolutionized the treatment of HCV in both the general population as well as those patients with advanced chronic kidney disease and receiving dialysis. These new treatment protocols are very well tolerated with limited side effects and manageable drug‐drug interactions while achieving remarkable sustained viral response rates. It is important that nephrologists become familiar with the differing strategies available for HCV‐infected ESRD patients so that the appropriate decision of when and who to treat can be made for each patient.     

Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct‐Acting Antiviral Agents

The direct‐acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end‐stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon‐free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy‐proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon‐based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment‐related side effects.     

The road map toward an hepatitis C virus‐free transplant population

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)‐based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN‐based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second‐generation direct‐acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN‐based therapy. These agents have the potential to reduce the number of patients developing HCV‐related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real‐world experience.     

Beyond hepatorenal syndrome: glomerulonephritis in patients with liver disease

Liver disease is frequently associated with renal abnormalities. In liver cirrhosis, impaired hepatic clearance of immune complexes leads to their trapping in the kidney, causing the lesions of hepatic immunoglobulin A (IgA) nephropathy and hepatic glomerulosclerosis. Chronic hepatitis C virus (HCV) infection can induce cryoglobulinemia type II with membranoproliferative glomerulonephritis, whereas chronic hepatitis B virus (HBV) infection may cause membranous nephropathy, or, more rarely, polyarteritis nodosa. Treatment aims at eliminating the viral infection, in HCV infection with interferon alfa and ribavirin and in HBV infection with interferon alfa or lamivudine. Short-term immunosuppressive treatment may be indicated in patients with severe inflammation. In alpha1-antitrypsin deficiency with liver disease a membranoproliferative type of glomerulonephritis can occur. In addition, partial or complete deficiency is frequently observed in patients with c-ANCA-positive systemic vasculitis.     

Hepatitis C virus infection in end‐stage renal disease and kidney transplantation

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end‐stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV‐positive/ESRD and HCV‐positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct‐acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV‐negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV‐related liver disease.     

Colorectal carcinoma metastasis in livers infected with hepatitis B or C virus

AIM: Metastases from colorectal cancers rarely occur in injured livers, however in western countries this phenomenon has not been investigated in patients with various forms of chronic hepatitis. Therefore in this study we evaluated the incidence of synchronous hepatic metastases of colorectal carcinomas in patients with hepatitis B (HBV) or C (HBC) infection. METHODS: Six hundred and thirty patients undergoing surgical treatment for colorectal carcinomas were analysed: the clinicopathological data of 87 patients with HBV or HCV infection (there were 29 patients with hepatitis C infection and 58 with hepatitis B infection) were compared to those of 543 non infected patients. RESULTS: Patients distribution was similar in both groups in terms of gender, age, type of operative procedures performed, histological grading and lymph node metastases. Stage I, II or III tumours were similarly represented in non infected and infected patients, while stage IV tumours were 33.1% in the non infection group and 17.2% in the infection group (P < 0.001). At the time of surgery, synchronous extrahepatic metastases were present in 14.9% of non infected patients and 15% of infected patients, while synchronous hepatic metastases were found in 32% and 17.2% of patients respectively (P < 0.01). CONCLUSIONS: Results of our study show that synchronous hepatic metastases of colorectal cancers are less frequently observed in chronic HBV or HCV infected patients than in non infected patients, while the incidence of extrahepatic metastases is comparable in both groups, suggesting that virus-related mechanisms and specific liver mediated immunity may have a protective role against neoplastic cell colonization of the liver.     

DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

A Six‐Year Follow‐Up After Interferon‐Alpha Monotherapy for Chronic Hepatitis C Infection in Hemodialysis Patients

Interferon‐alpha (IFN) has been accepted as an effective treatment for chronic hepatitis C virus (HCV) infection in hemodialysis (HD) patients. We prospectively assess the long‐term clinical, biochemical, and virological effects of interferon in the treatment of HD patients with chronic HCV infection. This study was performed in 20 HCV‐RNA‐positive HD patients with evidence of chronic hepatitis on liver biopsy. The patients received IFN administered after HD sessions in doses ranging from 3 to 6 million units for 6 to 12 months. The patients were followed up for a period of 6 years with determinations of serial alanine aminotransferase (ALT) levels and serum HCV‐RNA. At the time of the final follow‐up, the patients had no cirrhosis or hepatocellular carcinoma. Among the nonresponder group, only 1 patient died due to sudden cardiac death. Sustained normal serum ALT levels occurred in 9 (45%) of the patients. Nine patients had variable ALT levels, and 2 patients had persistently elevated ALT levels. Eight (40%) patients were continuously HCV‐RNA negative, whereas 12 patients (60%) had variable HCV‐RNA results at the end of the 6‐year follow‐up. These findings show that the long‐term clinical, biochemical, and virological response to interferon monotherapy is good in HD patients with HCV infection.     

A pleasant dilemma to have: to treat the HCV patient on the waiting list or to treat post‐liver transplantation?

New and relatively well‐tolerated medications to treat hepatitis C virus (HCV) infection have presented an opportunity for hepatologists to eliminate HCV in liver transplant (LT) candidates prior to transplantation. While concern for causing decompensated liver disease in the sickest subset of pre‐transplant patients makes some clinicians reluctant to offer treatment, we believe that several advantages of early HCV eradication appear to shift the debate in favor of using anti‐HCV agents before LT. There are encouraging safety data for new HCV medications in cirrhotic patients, and given the limited supply of donor livers available, delaying or possibly preventing the need for LT by treating HCV can offer significant benefit. Post‐LT, making immunosuppression management easier as well as avoiding both extrahepatic manifestations of HCV (e.g., diabetes mellitus and kidney disease) and the dilemma of distinguishing post‐transplant viral recurrence from allograft rejection makes earlier treatment of HCV especially appealing to clinicians. Furthermore, retrospective data have demonstrated a mortality benefit among HCV patients who are free of the virus at the time of LT. This article explores arguments for and against treating HCV in patients on the transplant list.     

Liver transplantation for HCV-related cirrhosis in a patient with gastric mucosa-associated lymphoma (MALToma) pretreated with rituximab.

End-stage liver disease due to chronic hepatitis C virus (HCV) infection is now the most frequent indication for liver transplantation. HCV infection is associated with extrahepatic disease including cryoglobulinemia and lymphoma. The number of patients requiring liver transplantation (LT) for cirrhosis secondary to HCV infection has increased over the past 10 years; consequently, associated extrahepatic manifestations (in particular hematological malignancies) will be more commonly observed in this patient group. The management of patients with both end-stage liver disease and significant HCV-related extrahepatic disease is undefined. We report a 59-year-old man in whom extranodal marginal-zone B-cell lymphoma arising in gastric mucosa-associated lymphoid tissue (MALToma) was successfully eradicated by rituximab administration and gastrectomy at LT for HCV-related cirrhosis. Our experience with rituximab in this patient suggests that it can be used safely in the setting of severe liver disease due to HCV infection. Rituximab may be useful in preventing progression of NHL until surgical extirpation is possible.     

When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Hepatitis C virus (HCV ) infection, a major cause of end‐stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin‐based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon‐free direct‐acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients. A recently approved, pan‐genotypic, direct‐acting antiviral regimen, glecaprevir and pibrentasvir, may simplify prescribing. The simplicity of these new therapies, with few side effects, makes it possible for nephrologists to treat HCV infection in their patients on dialysis. We review the workflow and motivation behind nephrology‐led management of HCV infection. We highlight the importance of identifying which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist. Nephrologist involvement would lead to improved access to treatment and ensure that appropriate patients are referred for HCV treatment. In this paper, we review the background of HCV infection, its effect on dialysis patients, and impact on kidney transplantation. In addition, we outline the therapy options for each genotype of HCV , and we discuss the benefits and barriers to nephrology‐led HCV treatment.     

Should all dialysis patients with hepatitis C be treated? If so,before or after kidney transplantation?

HCV infection by genotype 1 and 4 can now be cured in close to 100% of patients with stage 4 or 5 CKD, including dialysis patients. Several regimens are available, all interferon‐free and given for only 12 weeks. Thus unless life expectancy is short, HCV infection should be treated. The optimal timing of antiviral treatment will be dependent on several parameters: the possibility of being transplanted rapidly (either with a HCV+ graft or from a living donor) calls for treatment after transplantation. On the contrary, severe liver fibrosis, especially with portal hypertension calls for immediate treatment of HCV. Finally specific HCV genotype also impacts the treatment decision as genotypes 2,3,5 and 6 currently can be treated more easily after restoration of kidney function rather than in the presence of severe CKD, although this is anticipated to change soon once newer pangenotypic regimens are licensed.     

Effects of pegylated interferon α-2a on hepatitis-C-virus-associated glomerulonephritis

Hepatitis C virus (HCV) infection leads to chronic liver disease, but it has also been associated with extrahepatic manifestations. Membranoproliferative glomerulonephritis (MPGN) is the most common renal disease associated with HCV. Although renal disease related to HCV in adults has been well studied, it has not been well studied in children because it is rare. A recent study found that antiviral therapy was effective for adult patients with HCV-associated MPGN. We report a 9-year-old girl with HCV-associated MPGN. Her HCV genotype was 1b, and her virus load was high. The first renal biopsy showed mesangial proliferation and partial double contours of the basement membrane on light microscopy and immunofluorescence staining with immunoglobulin (Ig) M, IgG, and C3. The patient was successfully treated with pegylated interferon (IFN) α-2a monotherapy. The antiviral therapy was generally well tolerated. After antiviral therapy, a sustained virological response—defined as negative HCV ribonucleic acid (RNA) at least 24 weeks after antiviral treatment—was achieved, the proteinuria disappeared, and the second renal biopsy showed improvement.     

直接抗病毒药物治疗六例丙型肝炎病毒相关性皮肤损害患者的回顾性研究

目的探讨基于索磷布韦方案治疗丙型肝炎病毒（HCV）相关性皮肤损害的疗效和安全性。 方法回顾性分析2016年2月至2019年9月西安交通大学第二附属医院收治的6例HCV相关性皮肤损害患者接受基于索磷布韦方案治疗的效果和安全性。评估其持续病毒学应答（SVR12）率，治疗过程和治疗结束后肝功能和皮损症状的变化以及安全性。 结果6例患者年龄25～56岁；其中5例女性；2例肝硬化；3例基因型为HCV 1b，3例基因型为HCV 2a。皮损分别表现为阴囊湿疹、结节性痒疹、结节性红斑、扁平苔藓、干燥综合征和混和冷球蛋白血症相关皮损。2例患者病理确诊为HCV相关性皮损，4例患者临床诊断为HCV相关性皮损。患者接受索磷布韦/维帕他韦（3例）、索磷布韦/雷迪帕韦（2例）12周或索磷布韦/利巴韦林（1例）24周治疗。与基线水平相比，治疗结束或随访12周的丙氨酸氨基转移酶（ALT）显著降低、白蛋白（ALB）不变或升高，6例患者均获得SVR12且皮损均明显缓解。3例患者（阴囊湿疹、结节性痒疹、干燥综合征）皮损完全治愈，其他皮损包括结节性红斑、扁平苔藓、混和冷球蛋白血症相关皮损明显缓解，但需要接受免疫抑制剂和（或）细胞毒药物维持治疗。治疗期间未出现明显不良反应，随访期间皮损无复发。 结论HCV可引起不同的肝外皮肤表现，基于索磷布韦的无干扰素方案治疗HCV相关皮肤损害有效且安全性良好。对于皮肤疾病经对症治疗后效果欠佳者，需要尽早行HCV筛查，确诊HCV感染后建议尽快给予抗病毒治疗。     

Direct‐acting antivirals are effective and safe in HCV/HIV‐coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study

Direct‐acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV‐coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV‐coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV‐monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV‐coinfected patients had a median (IQR) CD4 T‐cell count of 366 (256‐467) cells/µL. HIV‐RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV‐RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon‐free regimens with DAAs for post‐LT recurrence of HCV infection in HIV‐infected individuals were highly effective and well tolerated, with results comparable to those of HCV‐monoinfected patients.     

Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis throughout the world. Several extrahepatic manifestations, including glomerulonephritis, have been reported to be associated with this type of infection. Cryoglobulinaemic and non-cryoglobulinaemic membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) are the commonest lesions associated with HCV. Results of treatment of these patients with interferon therapy have been disappointing, since relapse of the viraemia and subsequent relapse of the renal disease are major problems. Combination of interferon with ribavirin in patients with chronic liver disease has been shown to increase the rate of sustained response. METHODS: In this work, 20 patients with HCV-associated glomerulopathy were subjected to an in-depth evaluation of their kidney lesions and HCV involvement. Laboratory, histopathological, immunohistochemical, and electron-microscopy techniques were used. The patients received interferon therapy for 12 months; in interferon-resistant subjects, interferon was combined with ribavirin. RESULTS: MPGN was the commonest kidney lesion, being reported in 85% of these cases, followed by MN and mesangioproliferative glomerulonephritis (10 and 5% respectively). Mixed cryoglobulinaemia was encountered in 60% of the cases. Twelve months' anti-viral treatment resulted in aviraemia in 25% of cases, while liver enzymes were normalized in 75%, 24-h proteinuria significantly decreased (from median 4 g to 1.10 g, P=0.001), serum albumin increased (from median 2.50 to 3.55 g/dl, P=0.012), lower viral titres (from median 1.15 to 0.53 mega-Eq/ml, P=0.049), and C3 and C4 concentrations returned to normal. Basal serum creatinine and viral titres were important determinants of response to treatment. CONCLUSION: This study supports the relationship between HCV and glomerulonephritis, especially MPGN, and the use of a combination of interferon and ribavirin in the treatment of selected cases of HCV-related glomerulopathy.     

OncoSurge: a strategy for long‐term survival in metastatic colorectal cancer

OncoSurge is a combined modality strategy for the management of colorectal cancer with hepatic metastases. It has emerged as a result of new and expanded patient selection criteria for resectability of metastases, coupled with more effective neoadjuvant and postoperative chemotherapy. By bringing together these developments in surgery and medical oncology, the new approach promises to increase significantly the resectability rate and long‐term survival in colorectal cancer patients with liver metastases. Surgery for colorectal liver metastases should now be considered across a range of clinical circumstances that would historically have been contraindications to resection. These contraindications include multiple or bilobar metastases, large tumour size, a Dukes stage C or poorly differentiated primary tumour, synchronous detection of metastases with the primary tumour, disease in elderly patients, or a resection margin of less than 1 cm. None of these criteria should necessarily exclude a patient from resection, because although they may be associated with a less favourable prognosis they do not exclude the possibility of long‐term survival. Non‐resectable extrahepatic disease and portal lymph node involvement, however, remain contraindications to resection in most circumstances. Retrospective studies of neoadjuvant therapy have indicated that a regimen based on low dose oxaliplatin, 5‐fluorourucil (5‐FU) and leucovorin increased the overall resectability rate of patients presenting with hepatic colorectal metastases from 20% to 30%, with 13.6% of patients with unresectable metastases becoming eligible for curative resection. More recently, studies using more potent oxaliplatin‐based regimens have reported significantly higher resectability rates of at least 40%, with 5‐year survival of 50% reported in one large study among patients whose liver metastases were resected after initial neoadjuvant therapy for unresectable tumours. Following resection, postoperative therapy based on a combination of hepatic artery infusion (HAI) and systemic chemotherapy reduces hepatic recurrence and increases survival, but more potent systemic therapy is required to reduce the rate of extrahepatic recurrence. Studies are now in progress combining HAI with oxaliplatin‐based systemic therapy to address this issue. By combining a more inclusive approach to surgery with more effective neoadjuvant and postoperative chemotherapy, the OncoSurge treatment model is likely to increase significantly the number of patients with hepatic colorectal metastases who can be treated with curative intent, and thus has the potential to improve overall patient survival.     

Acquired hepatocerebral degeneration in hepatitis C infection

Patients with chronic liver disease (CLD) often have neurological sequelae, of which hepatic encephalopathy is the most frequent and reversible. Rare irreversible complications of CLD are acquired (non Wilsonian) hepatocerebral degeneration (AHCD) and hepatic myelopathy (HM). To our knowledge, AHCD has rarely been reported in patients with hepatitis C virus (HCV) infection. We report a patient with HCV infection who developed AHCD and resulted in serious complications.