Transplanting organs from hepatitis B positive donors: Is it safe? Is it ethical?

Liver transplant centres throughout the USA face a huge shortage of liver organs for their wait‐listed patients. Various types of innovations are being considered for expansion of this donor pool. Organs that were previously deemed to be high risk are now being considered for transplantation. For the last 25 years, hepatitis B core antibody (anti‐HBc+) organs have been used for liver transplantation. While the initial transplantations did reveal a high incidence of de novo hepatitis (DNH) in the recipients, the medical knowledge and experience have evolved and this risk has been markedly decreased. In this paper, medical literature evaluating the safety of such organ transplants has been reviewed. There is strong evidence to suggest that using anti‐HBc+ organs with appropriate prophylaxis after transplant is a safe practice with good patient and graft survivals. In the second half of the paper, we discuss whether it is ethical to use anti‐HBc+ organs. We argue that the use of such organs is in compliance with the principles of medical ethics and that society at large benefits from the use of these organs. Hence, we recommend that the use of such organs is both safe and ethical and this practice should be continued in the future.     

Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

BACKGROUND: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.     

Occult hepatitis B virus infection: a covert operation

Summary. Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus‐specific nucleic acid does not always translate into infectivity, and the occurrence of primer‐generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti‐HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti‐HBc) positive (±anti‐HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16‐guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti‐HBc reaction or a detectable HBV DNA.     

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C

Background: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV‐DNA detection. Aims: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. Methods: This cross‐sectional study included hepatitis B surface antigen‐ and human immunodeficiency virus‐negative subjects with positive HCV‐RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV‐DNA using a commercial assay. The METAVIR system was used for histological analysis. Results: One‐hundred and eleven patients were evaluated. Thirty‐one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti‐HBc). HBV‐DNA was not detected in any sample. Anti‐HBc‐positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti‐HBc‐positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti‐HBc‐negative subjects who acquired HCV before the age of 30 and in 57% of those anti‐HBc‐positive patients who were infected by HCV after 30 years of age (P<0.001). Conclusion: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.     

De novo acute hepatitis B infection in a previously vaccinated liver transplant recipient due to a strain of HBV with a Met 133 Thr mutation in the “a” determinant

Abstract: De novo HBV infection post‐liver transplantation (LT) from an anti‐HBc seropositive donor rarely presents as acute failure. We report a 42‐year‐old Caucasian female, HBsAg and anti‐HBc seronegative, with primary biliary cirrhosis who received an allograft from a HBsAg negative, anti‐HBc seropositive donor. The patient, previously vaccinated years pre‐LT, was re‐vaccinated against HBV and 1 year post‐LT had an anti‐HBs titre of 256 IU/l. Two years post‐LT, elevated serum aminotransferases and worsening liver function with an INR of 2.0 developed. The HBsAg became positive, anti‐HBs undetectable and serum HBV‐DNA >2000 pg/ml by hybridisation assay. Liver biopsy revealed significant ballooning degeneration, piecemeal necrosis and positive immunostaining for HBsAg. Progressive liver failure developed followed by sepsis and terminal multi‐organ failure. Subsequent analysis of the predominant HBV strain revealed mutations in the “a” determinant: Met 133 Thr (codon change ATG to ACG) and Asn 131 Thr. Conclusion: Acute de novo HBV infection from an anti‐HBc sero‐positive donor may occur long after LT despite protective anti‐HBs titres post‐vaccination secondary to the emergence of “a” determinant mutated strains of HBV.     

PNPLA3 as a liver steatosis risk factor following living‐donor liver transplantation for hepatitis C

Aim

Liver steatosis frequently occurs following liver transplantation (LT) and can affect patient outcome. Here, we aimed to clarify the steatosis and steatohepatitis risk factors that apply after living‐donor LT for chronic hepatitis C.

Methods

We retrospectively examined 43 transplant recipients and donors, and tested for single nucleotide polymorphisms in the PNPLA3 gene. Liver biopsies taken 1 year after transplantation and yearly thereafter, or when abnormal liver enzyme levels were detected, were examined by histopathology.

Results

Liver steatosis (>5% steatotic hepatocytes) was evident in 13 of 43 cases (30%), and steatohepatitis in 3 (7.0%). The average time to steatosis after LT was 2.74 ± 1.55 years. The PNPLA3 rs738409 GG genotype, a steatosis risk factor, was identified in 13 recipients and 10 donors. Steatosis prevalence did not differ according to recipient genotype. However, this condition was significantly more common among patients who received tissue from donors carrying the rs738409 GG genotype compared to those with grafts from donors of the CC or CG genotype (60, 7, and 26%, respectively; P < 0.05). All 3 steatohepatitis cases were associated with the GG donor genotype.

Conclusion

The PNPLA3 rs738409 GG donor genotype affects liver steatosis and steatohepatitis risk following living‐donor LT.     

Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors

The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post-transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8–10 hours, and donor age 50–60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor.

BACKGROUND/AIMS: Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). METHOD: Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. RESULTS: To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. CONCLUSIONS: Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis.     

Meta‐analysis of the association between anti‐HBc seropositivity and a poor prognosis of chronic HCV infection

Aim: The impact of serological HBsAg? and anti‐HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti‐HBc positivity imposes any effect on the course of HCV‐related chronic liver disease. Methods: We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow‐up of all cohort studies. Results: Eighteen references were included in this study, of which four were cohort studies. Twelve studies were retrospective, observational and non‐interventional studies. According to our meta‐analysis, the rate of serological HBsAg? and anti‐HBc+ was higher among HCC patients compared with non‐HCC patients (odds ratio [OR], 1.55; 95% CI, 1.22–1.98). HCV patients that were anti‐HBc+ had a greater chance of developing HCC than their anti‐HBc? counterparts (OR, 2.15; 95% CI, 1.34–3.47). Conclusions: The serological status of HBsAg? and anti‐HBc+ appears to be correlated with a poor prognosis for chronic HCV infection. Though the general quality of these references was low, and multiple confounding factors existed, the likelihood of a poorer outcome of HCV patients that are positive for anti‐HBc should be considered by their physicians.     

Changing aetiology of liver dysfunction in the new generation of a hepatitis B and C‐endemic area: cross‐sectional studies on adolescents born in the first 10 years after universal hepatitis B vaccination

Background/Aim: Geographical variation in viral hepatitis infection complicates various levels of liver diseases. This study elucidates the changing aetiology of alanine transaminase elevation (ALT levels >40 IU/L) in a previously hepatitis‐endemic township. Design/Methods: Five cross‐sectional screenings were performed on teenagers born from 1984 to 1993. We examined hepatitis B surface antigen (HBsAg), anti‐hepatitis C virus (anti‐HCV), ALT and body mass index, and additionally checked hepatitis B envelope antigen (HBeAg) for positive HBsAg and HCV RNA for positive anti‐HCV. Teenagers with ALT elevation underwent an ultrasonography examination. Results: This study enrolled 1788 (93.7%) of 1909 students, discovering individual prevalence of HBsAg (6.3%), anti‐hepatitis B core (anti‐HBc) (15.5%), anti‐HCV (2.2%), overweight (22.4%), obesity (12.8%) and ALT >40 IU/L (3.7%). HBsAg and anti‐HBc prevalence declined with trends, while obesity increased with trends (P<0.001). Among 66 ALT‐elevated teenagers, prevalence percentages of risk factors were HBsAg (22.7%), anti‐HCV (1.5%), obesity (45.5%), HBsAg with obesity (7.6%) and anti‐HCV with obesity (3.0%). Additionally, obesity showed predominance (85.7%) among aetiologies of teenagers with fatty livers (60.9%). The independently associated factors of ALT elevation included being male (odds ratio, 2.18; 95% confidence interval, 1.21–3.93), HBsAg (4.25; 1.06–17.13), HBeAg (7.24; 1.64–31.9), HCV RNA (29.03; 5.8–145.29) and obesity (16.5; 8.79–30.98). Conclusion: In place of viral hepatitis, obesity is becoming the major aetiology of abnormal liver function among the young generation in a previously hepatitis‐endemic area.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.     

Epidemiology,serological markers,and hepatic disease of anti-HCV ELISA-2-positive blood donors

The epidemiology associated with hepatitis C virus (HCV) infection, serologic reactivity, and hepatic disease related to anti-HCV-positive donors of Granada were researched. From 1990 through 1993, medical and epidemiological information and anti-HCV and HCV RNA testing were evaluated in 46,741 blood donors. Serum samples were obtained for anti-HCV ELISA and RIBA and HCV RNA determination. A liver biopsy was conducted in all anti-HCV positives by confirmatory second-generation RIBA to analyze the hepatic lesion and the presence of HCV RNA. The anti-HCV prevalence was 1.12%. A total of 228 anti-HCV second-generation ELISA positive blood donors were analyzed. Intrafamiliar transmission rate was 1.7%. Transfusion and intravenous drug abuse (IVDA) antecedents were associated with a higher risk of seroconversion. A RIBA-positive result was related to high second- and third-generation ELISA ratios (90%), HCV RNA positivity (89%), and elevated alanine aminotransferase (ALT) levels (88%). Approximately 50% of donors with normal ALT levels had high ELISA ratios and second-generation RIBA and HCV RNA positive results. Of the second-generation RIBA indeterminate results, 42% and 82% of the c22 and 33% and 100% of the c100 reactivities were third-generation RIBA and HCV RNA positive, respectively. Liver biopsy was conducted in 85 donors, 74% of whom had a chronic hepatitis and 83% had detectable HCV RNA levels. Chronic hepatitis was diagnosed in 88% vs 43% of donors with elevated and normal alanine aminotransferase levels, respectively. ELISA and confirmatory HCV RNA determinations should be routinely employed in donor screening. A liver biopsy should be conducted in patients with elevated ALT levels and normal ALT levels when viremic.     

Acute hepatitis C virus (HCV) infection in chronic carriers of hepatitis B virus (HBV): the impact of underlying active HBV replication on persistence of HCV infection and antibody responses to HCV

BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.     

慢性肝炎受者肾移植术前肝活检的临床价值

目的：了解慢性肾衰（ＣＲＦ）合并病毒性肝炎患者肾移植前肝活检的安全性及临床价值。方法：分析１９９６年元月至１９９８年６月我院２４例ＣＲＦ合并慢性病毒性肝炎患者肾移植前行经皮肝活检的安全性及组织病理结果。其中１４例接受肾移植并对其进行长期随访。结果：２４例患者肝活检的成功率１００％。并发症的发生率为３３．３％，需输血治疗者４例（１６．７％）；无一例需手术治疗或死亡。２４例急诊中，明确诊断为慢性乙型肝     

Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C

Background/Aims: The role of liver biopsy has been questioned in the management of patients with hepatitis C viral (HCV) infection. The aims of this study were to determine the impact of clinical parameters and degree of inflammation and steatosis on liver fibrosis. Patients/Methods: Clinical data and liver histology findings in 510 HCV patients were analysed. Results: Hepatitis C virus genotype 1 (GT‐1) was found in 38%, GT‐2 in 15% and GT‐3 in 45% of patients. In liver biopsy specimens, inflammation activity was present in 68%, increased fibrosis in 19% and marked steatosis in 17% of patients. Independent clinical risk factors for the increased fibrosis were patients' age at biopsy, body mass index (BMI) and duration of HCV. Steatosis and inflammation activity were independent histological risk factors for fibrosis only in GT‐1; in GT‐3, only inflammation correlated independently with fibrosis. Conclusions: Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in GT‐1. When scoring liver biopsies of HCV patients, the degree of steatosis should be included in addition to fibrosis and inflammation activity.     

Donor screening for hepatitis B virus infection in a cell and tissue bank

Abstract: Background and objectives. Hepatitis B virus (HBV) has been transmitted by tissue transplantation. In order to reduce the risk of HBV transmission, testing for antibody to HBV core antigen (anti‐HBc) is used in addition to testing for hepatitis B surface antigen (HBsAg) in many blood centers and tissue banks. Design and methods. We retrospectively analyzed the results of HBV assays in tissue donors. All tissue donors were tested for HBsAg and anti‐HBc. All anti‐HBc positive sera were tested for the antibody to HBsAg (anti‐HBs). From July 2006, an HBV nucleic acid testing (NAT) assay was also performed. Results. A total of 6855 tissue donors from January 1999 till July 2007 were tested for HBV assays: 4756 women and 2099 men. Positive HBsAg was found in 23 (0.36%) living donors, while no multiorgan or cord blood (CB) donor was found to be positive for HBsAg. Positive anti‐HBc was found in 80 multiorgan donors (12.94%), 599 living donors (17.84%), and 103 CB donors (3.57%) (P<0.005), while isolated anti‐HBc was found in 12 multiorgan (1.94%), in 126 living tissue donors (3.75%), and in 8 CB donors (0.28%). A total of 1310 donors were analyzed for single‐sample DNA HBV NAT assay. Discussion. We consider that anti‐HBc and NAT assays must both still be performed in addition to HBsAg assay for HBV screening in tissue donors. All these tests will be useful in order to define an algorithm for safe and efficient management of the tissue bank.     

Transmission of viral hepatitis by kidney transplantation: donor evaluation and transplant policies (Part 1: hepatitis B virus)

Abstract: This two-part article discusses serologic testing of prospective donors for viral hepatitis B and C as part of the comprehensive donor evaluation and reviews of the current policies and practices aimed at preventing donor-to-recipient transmission of hepatitis B and C viruses (HBV, HBC). This second part of the review discusses HCV. Organs procured from HCV-infected donors can transmit the virus to their recipients. Because a number of studies have associated infections with HCV with increased morbidity and mortality among renal transplant recipients, it is important to prevent HCV transmission with renal transplantation. The majority of organ procurement organizations (OPOs) perform routine screening of organ donors for antibodies to HCV (anti-HCV). The prevalence of HCV infection among cadaver organ donors, ascertained based on a positive anti-HCV test by ELISA2, varies worldwide between 1.08% and 11.8%. The use of kidneys from donors negative for anti-HCV by ELISA2 carries negligible or no risk of transmitting HCV infection. The use of organs from anti-HCV-positive donors has been restricted to life-saving transplants (heart, liver or lung) by the majority of OPOs worldwide. However, discarding kidneys from all anti-HCV positive donors would lead to unnecessary waste of organs because not all anti-HCV positive donors are infectious. Recently, the policy of unconditional restriction on the use of kidneys from anti-HCV positive donors has been challenged, and transplantation of organs from anti-HCV-positive donors into anti-HCV-positive recipients has been found to be safe. An even better alternative might be a policy of transplanting kidneys from anti-HCV-positive donors only in HCV RNA-positive recipients. However, until more data become available, these two strategies remain experimental treatments.     

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.     

Hepatitis delta virus propagation enabled by hepatitis C virus—Scientifically intriguing,but is it relevant to clinical practice?

In vitro cell culture experiments and animal models have demonstrated that hepatitis delta virus (HDV) can theoretically propagate being enveloped by human pathogenic viruses other than hepatitis B virus (HBV), namely hepatitis C virus (HCV) and dengue virus. However, the clinical relevance of these findings and whether HDV replication occurs in real‐world hepatitis B surface antigen (HBsAg)–negative HCV patient cohorts remain unknown. To this aim, we analysed 323 HCV‐RNA–positive and HBsAg‐negative sera for the presence of HDV‐RNA and anti‐HDV antibodies (anti‐HDV). All 323 (100%) samples were negative for HDV‐RNA. Interestingly, 8/316 samples tested positive for anti‐HDV. The HBV serology of these eight patients showed a positive result for HBV core antibodies (anti‐HBc) indicating a seroconversion of an acute HBV infection in the past. None of the anti‐HBc–negative patients were positive for anti‐HDV. Our results indicate a distinctly low probability of replicative HDV infection in HCV mono‐infected patients in Germany. Current German clinical guidelines rightly recommend performing HDV screening only in HBsAg‐positive patients. However, larger studies on this subject should be performed in regions that are endemic for chronic HBV/HDV as well as HCV infections.