There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E.

Cancer remains a significant cause of morbidity and mortality in kidney transplant recipients, due to long-term immunosuppression. Salient issues to consider in decreasing the burden of malignancy among kidney transplant recipients include pretransplant recipient evaluation, post-transplant screening and monitoring, and optimal treatment strategies for the kidney transplant recipients with cancer. In this review, we address cancer incidence and outcomes, approaches to cancer screening and monitoring pretransplant and post-transplant, as well as treatment strategies, immunosuppressive management, and multidisciplinary approaches in the kidney transplant recipients with cancer.

The availability of direct-acting antiviral (DAA) therapy might have impacted use of hepatitis C virus (HCV)-infected (HCV+) deceased donor kidneys for transplantation.

We used 2005 to 2018 Scientific Registry of Transplant Recipients data to identify 18 936 candidates willing to accept HCV+ kidneys and 3348 HCV+ recipients of HCV+ kidneys. We compared willingness to accept, utilization, discard, and posttransplant outcomes associated with HCV+ kidneys between 2 treatment eras (interferon [IFN] era, January 1, 2005 to December 5, 2013 vs DAA era, December 6, 2013 to August 2, 2018). Models were adjusted for candidate, recipient, and donor factors where appropriate.

In the DAA era, candidates were 2.2 times more likely to list as willing to accept HCV+ kidneys (adjusted odds ratio, 2.072.232.41; P < 0.001), and HCV+ recipients were 1.95 times more likely to have received an HCV+ kidney (adjusted odds ratio, 1.761.952.16; P < 0.001). Median Kidney Donor Profile Index of HCV+ kidneys decreased from 77 (interquartile range [IQR], 59-90) in 2005 to 53 (IQR, 40-67) in 2017. Kidney Donor Profile Index of HCV- kidneys remained unchanged from 45 (IQR, 21-74) to 47 (IQR, 24-73). After adjustment, HCV+ kidneys were 3.7 times more likely to be discarded than HCV- kidneys in the DAA era (adjusted relative rate, 3.363.674.02; P < 0.001); an increase from the IFN era (adjusted relative rate, 2.783.023.27; P < 0.001). HCV+ kidney use was concentrated within a subset of centers; 22.5% of centers performed 75% of all HCV+ kidney transplants in the DAA era. Mortality risk associated with HCV+ kidneys remained unchanged (aHR, 1.071.191.32 in both eras).

Given the elevated risk of death on dialysis facing HCV+ candidates, improving quality of HCV+ kidneys, and DAA availability, broader utilization of HCV+ kidneys is warranted to improve access in this era of organ shortage.

Hepatitis C virus infection is associated with increased morbidity and mortality. It remains a major challenge for management and treatment, especially in patients with renal transplant. The new direct-acting antiviral agents gave big hopes to both clinicians and patients that they can overcome this challenge without major side effects. Studies recently have supported this claim; however, they are still few, limited, and may give false hopes. In the following case report, we present a case, supported by histological evidence about a possible acute rejection of kidney transplant after treatment with these new medications. This case is limited by the absence of donor-specific antibodies. This report is aimed to increase awareness about the urgent need for further studies.

Data from World Health Organization estimates that the hepatitis C virus (HCV) prevalence is 3% and approximately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%-100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV-positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases II, III clinical trials.

Hepatitis C virus (HCV) is a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Direct-acting antiviral agents (DAAs) have improved HCV management in CKD patients, however real-world clinical practice data are limited.

This study examined the prevalence of CKD among HCV patients receiving oral DAAs in a real-world setting. Comorbidities, early discontinuation rates, and healthcare costs were compared between patients with and without CKD.

Patients with HCV who were treated with oral DAAs between November 2013 and June 2015, and who were enrolled in a US health plan, were identified. Early discontinuation was calculated based on observed versus expected treatment duration, and expected treatment duration was based on genotype, initial treatment regimen, baseline cirrhosis, and prior treatments. Healthcare costs were calculated during the baseline, treatment, and post-treatment periods.

This study included 3438 patients receiving oral DAAs, of whom 6.9% had a CKD diagnosis. CKD patients were more often male (70.8 vs. 62.9%, p = 0.02) and older (mean age 62.0 vs. 58.8 years, p < 0.001) than non-CKD patients, and had a higher prevalence of most comorbidities. Among early discontinuers, CKD patients were more likely to experience anemia (19.4 vs. 7.7%, p = 0.028).

Few patients with CKD receive DAA treatment for HCV infections. HCV patients with CKD had significantly more comorbidities and higher baseline healthcare costs than patients without CKD. Compared with non-CKD patients, CKD patients were equally likely to discontinue DAA treatment early but had higher rates of anemia. This study highlights the need for more renal-friendly HCV therapies.

Chronic infection with HCV can rapidly progress to cirrhosis leading to increased mortality rates in immunosuppressed organ-transplanted patients. In liver-transplanted patients, the introduction of directly acting antivirals has modified HCV natural history by providing a safe and effective therapy for this group of patients. To date there are no data on safety and efficacy of IFN-free regimens in HCV patients who received lung transplant (LuT).

We report three patients who have received anti-HCV treatment after LuT with Sofosbuvir-based regimens.

All patients achieved a SVR, no unexpected safety signals were observed and no modifications in immunosuppressants were required.

Our report is the first to show that HCV patients who underwent LuT can be safely treated with IFN-free regimens, thus opening the door for refined clinical management of this category of patients.

A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody-mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection.

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.

Interferon-based therapy remains the gold standard for hepatitis C in patients with chronic kidney disease; however, due to the high rate of IFN-induced rejection after transplant, treatment of HCV-infected kidney transplant recipients is recommended only in particular circumstances. We report the case of a 45-year-old Caucasian female with chronic hepatitis C (genotype 1b) who returned to hemodialysis following the complete functional loss of her kidney transplant. She started combination antiviral therapy with peg-IFN-α2a (135 mcg sc weekly) plus ribavirin (200 mg daily) nine months after the re-initiation of hemodialysis. Antiviral therapy was neither effective nor safe; ribavirin was stopped at week 38 due to hemolytic anemia; on-treatment HCV breakthrough was observed at week 48; and acute rejection occurred after four months of IFN-based therapy. Diagnosis of acute allograft rejection was suspected on the grounds of clinical, radiographic, and laboratory data. Allograft nephrectomy was then performed and histology showed acute-on-chronic rejection. This is an uncommon case of IFN-associated kidney rejection in an allograft recipient who had functional loss of her graft and had returned to hemodialysis. In view of the risk of rejection of renal allograft, and the limited efficacy of IFN-based treatment of hepatitis C, physicians should be aware of effective treatment with oral anti-viral agents and avoid the use of IFN in patients on maintenance dialysis with failed renal allograft.

Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.

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.

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease after renal transplantation (RT), which reduces both graft and patient survival. After RT, the most widely used approach is interferon (IFN)-based therapy of hepatitis C which may be unsatisfactory with both poor efficacy and an increasing risk of allograft rejection. Thus, it is not recommended unless patients develop fibrosing cholestatic hepatitis. Several recent studies, however, suggest that treatment was possible with preservation of both renal and liver functions. From the limited studies on HCV infection after RT, several factors have been identified as important tools for the management of therapy in these patients. Infection with HCV genotypes 2 and 3, low baseline viral load and absence of advanced fibrosis/cirrhosis in the liver are associated with a sustained virologic response (SVR). After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of SVR independent of HCV genotype. Furthermore, some factors must be taken into consideration in order to avoid allograft rejection, such as the time between transplantation and therapy for HCV, the dose and duration of regimen and renal function. Careful evaluation of predictions of stable renal function and SVR for those patients helps to reduce inefficient treatment regimes and to increase the cure rate in addition to reducing the possible risk. In this review, the latest information was collected and we focus on the discussion of the factors influencing the attainment of SVR after RT.

Hepatitis E virus genotype 3 is not rare in developed countries, and may cause chronic hepatitis in immunocompromised patients. This may not only lead to abnormalities in liver test and malaise, but to severe neurological symptoms as well. In this case, chronic hepatitis E infection caused encephalopathy, an atactic gait, Lhermitte's sign, incomplete bladder emptying and peripheral sensory neuropathy in a renal transplant recipient. The diagnosis was not performed until years after the onset of first symptoms and several months after the onset of neurological symptoms. If treated adequately, viral load can be reduced in over two-thirds of patients and neurological symptoms are often resolved. More widespread knowledge about this virus and its extrahepatic manifestations may lead to a quicker diagnosis, and may limit pathology. Serological screening should be added to standard pretransplant virological screening, so that, in the future, patients without antibodies could be vaccinated.

Chronic hepatitis C virus (HCV) infection exists in a large proportion of patients undergoing renal transplantation. Nowadays it is not considered to be an absolute contraindication to transplantation; however, it is associated with an increased risk for the patient and accounts for a shorter half-life of the renal allograft. We present three transplant recipients who displayed serious hepatic dysfunction after renal transplantation due to an HCV infection. In two of these cases, the liver biopsies established the diagnosis of FCH. In the third case, the liver biopsy was compatible with the early stages of FCH. All patients were started on peg-interferon alfa 2-b and ribavirin with subsequent normalization of hepatic function and early complete viral responses.

Many liver diseases coexist with chronic renal disease, because many systemic conditions affect both the liver and the kidneys. Certain liver diseases are also common in patients with chronic renal disease, especially viral hepatitis, either because the renal disease occurs as a complication of viral hepatitis, or the viral hepatitis is acquired as a result of dialysis. Renal tubular dysfunction is also frequently observed with cholestasis. However, liver complications of renal diseases are extremely uncommon, notable examples include nephrogenic ascites and nephrogenic hepatic dysfunction. Nephrogenic ascites can mimic liver cirrhosis with ascites, and it improves with renal transplantation. Nephrogenic hepatic dysfunction is a manifestation of renal cell carcinoma, which settles with the removal of the renal cell carcinoma, but returns with the recurrence of the tumor. In general, the presence of liver disease in patients with chronic renal disease makes management of both conditions more challenging. Viral hepatitis should be treated, if possible, before renal transplant. If cirrhosis is present, renal transplant alone is contraindicated; combined liver and kidney transplantation is indicated in patients with end-stage renal disease and advanced cirrhosis.

Hepatitis C virus (HCV) infection is the leading indication for liver transplantation and a major cause of graft failure. This study investigated whether cyclosporin A (CsA), a widely used immunosuppressant for organ transplantation, inhibits full cycle HCV replication and restores type I interferon (IFN) signaling pathway in human hepatocytes. CsA treatment of hepatocytes before, during, and after HCV infection significantly inhibited full cycle viral replication, which is evidenced by decreased expression of HCV RNA, protein, and infectious viruses in human hepatocytes. The suppression of HCV replication by CsA was associated with elevated levels of endogenous IFN-α in infected hepatocytes. Although CsA had little effect on IFN-α signaling pathway in uninfected hepatocytes, CsA treatment of HCV-infected hepatocytes specifically upregulated the expression of IFN regulatory factor-1 and inhibited the expression of suppressor of cytokine signaling-1 and protein inhibitor of activated signal transducers and activators of transcription-x, the primary negative regulators of IFN signaling pathway. These findings provide additional evidence to support the development of CsA-based prevention/treatment of HCV infection for transplant recipients.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most common and serious causes of liver damage in patients with chronic kidney disease (CKD). The natural histories of HBV and HCV infections in patients with CKD are not fully understood; however, recent evidence has emphasized the adverse effect of HBV and/or HCV infection on survival in this population. Chronic liver disease is the fourth most important cause of death after renal transplantation. The negative effect of HCV infection on survival among renal transplant recipients has been linked to liver dysfunction and extrahepatic complications, such as chronic glomerulonephritis, post-transplantation diabetes mellitus, chronic allograft nephropathy, and sepsis. The transmission of HCV by solid organ transplantation has been unequivocally demonstrated. Renal transplant recipients who receive kidneys from HCV-positive donors are at increased risk of death. Although several studies have shown that in patients with HCV infection and chronic renal failure renal transplantation is associated with better survival than is dialysis, recent clinical guidelines recommend that kidneys from HCV-infected donors should not be used in HCV-seropositive recipients without detectable HCV viremia. Monotherapy with conventional interferon has been suggested to be a useful treatment for hepatitis C infection in patients on dialysis. Although no evidence suggests that patients with CKD are more prone to suffer from hepatic toxic effects than individuals with normal kidney function, patients with CKD usually receive multiple medications; and drug interactions may, therefore, have a role in the pathogenesis of drug-induced liver disease in this population.

Hepatitis C virus (HCV) infection is the most frequent cause of liver disease after renal transplantation. Its clinical course is irrelevant in the short term, except for rare cases of fibrosing cholestatic hepatitis. However, in the long run, HCV infection can lead to major liver complications. Because interferon (IFN) is generally contraindicated in renal transplant patients, the best approach is to treat patients on dialysis. Until more information with pegylated-IFN is available, the use of alpha-IFN monotherapy is recommended. Most of the patients with sustained virological response remain HCV RNA negative after transplantation. HCV-positive renal transplant patients have a higher risk for proteinuria, chronic rejection, infections and post-transplant diabetes (PTDM). Long-term patient- and graft-survival rates are lower in HCV-positive patients. Mortality is higher, mainly as a result of liver disease and infections. HCV can contribute to the development of certain neoplasias such as post-transplant lymphoproliferative disease (PTLD). HCV infection is also an independent risk factor for graft loss. PTDM, transplant glomerulopathy and HCV-related glomerulonephritis can contribute to graft failure. Despite this, transplantation is the best option for end-stage renal disease in HCV-positive patients. Several measures to minimize the consequences of HCV infection have been recommended. Adjustment of immunosuppression and careful follow up in the outpatient clinic for early detection of HCV-related complications are mandatory.

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for over 1 million deaths resulting from cirrhosis and liver cancers. Extrahepatic manifestations are also relevant and include mixed cryoglobulinemia, lymphoproliferative disorders, and kidney disease. HCV infection is both a cause and a complication of chronic kidney disease, occurring largely in the context of mixed cryoglobulinemia. This infection also represents a major medical and epidemiologic challenge in patients with end-stage renal disease on renal replacement therapy with dialysis or transplantation. In these settings the presence of HCV correlates with higher rates of patient mortality than in HCV-negative subjects on dialysis or undergoing kidney transplant. The major concern is the lack of safe and effective drugs to treat HCV-infected patients with chronic kidney disease. Unfortunately, there are no large-scale clinical trials in this population, especially those receiving renal replacement therapy, so that strong evidence for treatment recommendations is scant. This review article provides the readers with the most recent insights on HCV infection both as cause and complication of chronic kidney disease, discusses pitfalls and limitations of current therapies, and reports on preliminary experience with novel therapeutic agents, as well as directions for future research.

Hepatitis C virus (HCV) infection is especially problematic in patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. Rates of HCV infection are higher among hemodialysis patients than in the general population, and several routes of transmission are thought to stem from the dialysis unit. Management of chronic hepatitis C is also more complicated in hemodialysis patients because of altered pharmacokinetics and a predisposition for drug-related toxicity, particularly ribavirin-induced anemia. Clinical trials of patients with chronic hepatitis C and healthy, functioning kidney grafts are rare because of the inherent dangers of graft rejection. As a result, most studies in patients with ESRD have focused on patients waiting for a kidney transplant. Additionally, because ribavirin is contraindicated in this patient population, many studies have examined monotherapy treatments. According to meta-analyses, conventional interferon alfa treatment yields a sustained virological response (SVR) rate of 37%, whereas studies of pegylated interferon alfa monotherapy have yielded SVR rates between 13% and 75%. Several small studies have also used the monitoring of ribavirin plasma concentrations or hemoglobin levels to facilitate the use of combination therapy. In light of the results from these clinical trials, we herein review treatment guidelines and recommend strategies to help optimize the treatment of patients with ESRD.

There remains a lack of clarity surrounding the most effective treatment options for patients with chronic hepatitis C and ESRD. Treatment can be effective with many patients attaining SVR; however, unfavorable tolerability with interferon alfa-based therapy remains a concern and thus close supportive care should be aggressively pursued to help maintain adherence.