Severe clinical course of de novo hepatitis B infection after liver transplantation.

The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.     

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.     

Changing of hepatitis B virus markers in patients with bone marrow transplantation

The hepatitis B virus (HBV) infection and its resulting hepatic abnormalities are very high in prevalence among the Taiwan population. They also seem to compose a major problem to patients subjected to bone marrow transplantation (BMT) due to intensive chemoradiotherapy. In this study, the sera of 42 patients were investigated before and after BMT to detect the presence of HBV markers and to test their liver function (LF). Being followed-up for 3-12 months after BMT, 12 out of 27 were found to have altered HBV markers according to the classification of the following: seroconversion of HBsAg, clearance of HBsAb, appearance of HBeAg, clearance of HBeAb, and acute hepatitis. Thirty-seven out of 42 patients (88.1%) were found in routine LF test to develop one or more abnormality; however, 90% of them turned normal within one year after BMT. Only one patient died of complications associated with fulminant hepatitis. In conclusion, the previous hepatic damage from HBV infection appears unlikely to increase the risk of posttransplant morbidity and mortality.     

Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow transplantation

To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) exposure on the incidence of those viral infections after bone marrow transplantation (BMT). The study included 63 patients presented to the BMT unit; 28 of them underwent transplantation and 35 were not transplanted. All serum markers of CMV, HBV, and HCV infections were monitored using ELISA technique, as well as PCR-DNA for CMV, HBV and HCV RT-PCR techniques for HCV. The incidence of active CMV and HCV was 11/28 (39%) and 6/28 (21%) in post-BMT recipients compared to 2/35 (6%) and 2/35 (6%) in the 35 untransplanted patients (P=0.00003 and P=0.05). Whereas active HBV infection was non significantly (P=0.13) higher 3/28 (11%) in the BMT patients in comparison to 1/35 (3%) in untransplanted patients. Ten out of the 19 (53%) of the CMV-seropositive recipients developed CMV reactivation compared to 1/9 (11%) of the CMV-seronegative recipients who developed CMV seroconversion. In addition, 3/8 (38%) of the HBV-seropositive recipients developed HBV reactivation in comparison to 0/20 of the HBV-seronegative recipients. Moreover, 5/13 (39%) of the HCV-seropositive recipients developed HCV reactivation in comparison to 1/16 (6%) of the HCV-seronegative recipients who developed HCV seroconversion. In conclusion, previous exposure to CMV, HBV, and HCV infections in the recipients of BMT patients were found to influence the risk of developing those viral infections.     

Case Report of Lamivudine-Resistant Hepatitis B Virus Infection Post Liver Transplantation from a Hepatitis B Core Antibody Donor

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novo hepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long-term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV infection developed more than 3 years after LT with a lamivudine-resistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novo post-LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti-HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.     

Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence

AIMS: We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS: Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.     

Differential Effects of Donor Age in Liver Transplant Recipients Infected With Hepatitis B, Hepatitis C and Without Viral Hepatitis

The variable impact of specific risk factors on survival outcomes based on pre-transplantation diagnosis was analyzed in adult liver transplant recipients reported to the Scientific Registry of Transplant Recipients: 778 with hepatitis B (HBV), 3463 with hepatitis C (HCV) and 7429 without viral hepatitis. Graft and patient survival for the HBV and no viral hepatitis groups did not differ significantly. The HCV group had significantly lower graft (p = 0.0019) and patient survival (p < 0.0001) than the no viral hepatitis group. Patient survival was significantly lower (p = 0.0011) for HCV compared to HBV patients; differences in graft survival approached significance (p = 0.0561). Donor age, which was not a risk factor in patients with HBV, was the strongest predictor of graft loss and death in patients with HCV, starting with donors >40 years. Donor age >60 years was the strongest predictor of graft loss and death in patients without viral hepatitis. The risks of graft loss and death were reduced for patients on tacrolimus-based immunosuppression with mycophenolate mofetil, regardless of disease etiology. There are clear differences in risk factors for poor outcomes based on underlying liver disease, particularly with regard to the impact of donor age.     

Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC,United States, 2014‐2017

We evaluated clinical outcomes among organ recipients with donor‐derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti‐HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti‐HCV and HCV RNA. Donor risk behaviors were abstracted from next‐of‐kin interviews and medical records. During 2014‐2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow‐up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow‐up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next‐of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.     

Living donor liver transplantation from hepatitis B core antibody positive donors

Liver allografts from donors previously exposed to hepatitis B virus (HBV) carry the risk of transmission of HBV infection to immunosuppressed recipients. However, exclusion of donor candidates with the serologic evidence of resolved hepatitis B-HBV surface antigen (HbsAg) negative and HBV core antibody (anti-HBc) positive-is not feasible in countries endemic for HBV. AIM: Our aim was to assess the safety of living donor liver transplantation from anti-HBc positive donors. MATERIALS AND METHODS: In our institution, 152 transplants were performed between June 1999 and April 2004. Fifty-six (37%) of the living donors were anti-HBc positive. Twenty of these liver grafts were transplanted to HbsAg-negative recipients. We excluded four HBsAg negative recipients who died because of early complications after transplantation. Lamivudine (100 mg/day) was given for prophylaxis of de novo HBV infection. RESULTS: The mean follow-up time for 16 HBsAg-negative recipients was 21.7 (7-48) months. None of them experienced de novo HBV infection. CONCLUSION: The use of liver allografts from anti-HBc-positive living donors is reasonably safe in HBsAg-negative recipients under lamivudine prophylaxis.     

Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation

Hepatitis B virus (HBV) prophylaxis is necessary to prevent de novo hepatitis B infection from HbcAb-positive donors. However, which protocol is more effective is somewhat controversial. Also, it is uncertain whether it is necessary to administer HBV prophylaxis for HbsAb-positive recipients. This study attempted to determine whether it is necessary to administer HBV prophylaxis for HbsAb-positive patients and to evaluate the efficacy of an HBIG monotherapy protocol. From May 1996 to July 2001, among 128 donors examined for HbcAb, 58 donors (45.3%) were HbcAb-positive. Eighteen HbcAb-positive grafts were transplanted to HbsAg-negative recipients. The 4 patients who died of unrelated causes were excluded from this study. Of 14 study cases, 12 recipients were HbsAb-positive, and 2 were HbsAb-naive. Prior to late 1998, we used HBV vaccination only for de novo infection prophylaxis. However, starting from December 1998, HBIG was administered from the time of the liver transplantation regardless of HBsAb positivity. The overall rate of de novo HBV infections from HbcAb-positive donors was 21.4% (3 of 14). All 3 recipients without HBIG prophylaxis presented with de novo HBV infections. Two were HbsAb-positive preoperatively. No de novo HBV infections occurred among recipients with HBIG prophylaxis. Therefore, it is essential to administer HBV prophylaxis even for vaccinated HbsAb-positive patients. HBIG monotherapy is effective to prevent de novo hepatitis B infections from HbcAb-positive donors in living donor liver transplantation.     

Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors

Exclusion of liver grafts from hepatitis B core antibody (anti-HBc) positive donors to prevent de novo hepatitis B virus (HBV) infection after liver transplantation is not feasible in areas highly endemic for HBV virus like Taiwan, where approximately 80% of adults are anti-HBc(+). The efficacy of lamivudine monotherapy to prevent de novo HBV infection after living donor liver transplantation (LDLT) using grafts from anti-HBc(+) donors remains to be elucidated. From June 1994 to August 2000, LDLT was performed in 42 recipients. Twenty-four of the 42 donors were anti-HBc(+) (57%). Pre-transplant HBV vaccination was given to all recipients irrespective of anti-HBc status at monthly intervals for 3 months. Until December 1997, eight recipients received liver grafts from anti-HBc(+) donors without prophylaxis. Since January 1998, prophylaxis with lamivudine monotherapy was given to 16 recipients receiving liver grafts from anti-HBc(+) donors. De novo HBV infection occurred in three of the eight recipients (37.5%) who did not receive prophylaxis, while none of the 16 recipients given lamivudine developed de novo HBV infection after a mean follow-up of 25 months. Two of the three recipients with de novo HBV infection were anti-HBs(-) and one recipient was anti-HBs(+). Lamivudine was well tolerated, and no side effects were noted. These results suggest that lamivudine monotherapy for recipients receiving anti-HBc(+) liver grafts is a simple, relatively inexpensive and effective prophylactic regimen for prevention of de novo HBV infection. The additive protection provided by vaccine-induced or natural immunity is uncertain.     

Hepatitis G virus infection in a haemodialysis unit: prevalence and clinical implications

Background. Hepatitis viruses have become one of the main infectious problems in patients on long-term haemodialysis. A new RNA virus, designated hepatitis G virus (HGV) has been recently identified. The pathogenic relevance of this virus is currently under investigation. The aim of this study was to analyse the prevalence and clinical implications of hepatitis G virus infection in patients on haemodialysis. Methods. The presence of HGV-RNA was investigated in 96 patients on maintenance haemodialysis. Hepatitis viral markers (HBsAg, anti-HCV, HGV-RNA) and liver tests were assessed in all these patients, as well as the risk factors for hepatitis viruses acquisition. As a control group, 200 blood donors were tested for the presence of HGV-RNA. Results. HGV-RNA was detected in 25 of 96 patients on haemodialysis (26%) and in six of 200 blood donors (3%) (P <0.001). Thirteen of 25 HGV infected patients (52%) were coinfected with other hepatitis viruses (HBV and/or HCV). Evidences of chronic liver disease were more frequent in patients infected by HBV and/or HCV (61%) than in patients infected by HGV alone (17%) (P = 0.01). Although 80% of HGV infected patients had received blood products, the transfusion rate was not different from non HGV-infected patients. Time on haemodialysis was significantly shorter in patients infected with HGV alone (3.1 ± 3.5 years) compared to patients infected with HBV and/or HCV (7.6 ± 5.8 years) (P = 0.04). Conclusions. Patients on maintenance haemodialysis are at increased risk for HGV infection. HGV infection itself does not seem to be a frequent cause of chronic liver disease in these patients. Since the prevalence of HGV infection in blood donors is high, blood transfusions could be one of the main factors implicated in HGV transmission in patients on haemodialysis.     

Clinical impact of GB-C virus in haemodialysis patients

Background: Haemodialysis patients run a high risk of acquiring viral hepatitis B (HBV) or C (HCV) infection. Recently a new parenterally transmittable RNA virus, designated GBV-C, was isolated. Methods: We therefore screened 277 patients on maintenance dialysis and 358 blood donors as a control group for GBV-C by nested PCR and correlated the data with AST, ALT, duration of dialysis, transfusion, renal transplants and coinfections with HBV and HCV. Results: The prevalence of GBV-C among haemodialysis patients was 7.9%, and 3.6% among blood donors. Neither duration of dialysis nor number of blood transfusions were associated with GBV-C infection, whereas GBV-C positive patients were significantly more often transplanted than GBV-C-negative individuals. Transaminases of GBV-C-positive individuals remained within normal limits in all haemodialysis patients and normal in all infected blood donors. Coinfections of GBV-C with HBV and HCV were only present in 0.7% and 1% respectively. Conclusions: We conclude that GBV-C virus infection is frequent among haemodialysis patients. Transaminases cannot serve as surrogate markers, and parenteral as well as community-acquired infection seems to be possible. Key words: GBV-C; haemodialysis; viral hepatitis      

Use of hepatitis B core antibody-positive liver allograft in hepatitis C virus-positive and -negative recipients with use of short course of hepatitis B immunoglobulin and Lamivudine

INTRODUCTION: With the shortage of donor organs, increasing number of hepatitis B core antibody (HBcAb)-positive [HBcAb(+)] liver allografts are being used for liver transplantation (LTx) in patients who are HBcab-negative [HBsAb(-)]. This study was aimed at assessing outcomes for hepatitis C virus (HCV)-positive [HCV(+)] and HCV-negative [HCV(-)] patients who received HBcAb(+) liver grafts from deceased donors and also received a short course of hepatitis B immunoglobulin (HBIg) with long-term lamivudine therapy after LTx. MATERIALS AND METHODS: From February 1995 through February 2003, 28 patients (mean age 53.8 +/- 10.2 years, 19 men and nine women, 16 HCV[-]; 12 HCV[+]) received HbcAb(+) liver allografts. All recipients received a short course of HBIg prophylaxis (10,000 units/day for 4 days) and long-term lamivudine 100 mg/d after LTx in addition to a tacrolimus-based immunosuppressive regimen. RESULTS: Seven (25%) of the 28 recipients died during follow-up and three recipients required retransplantation. Three recipients (10.7%) developed HBV infection during follow-up, one of whom died 36 months after LTx and the other two had YMDD mutant HBV. The overall 6-year actuarial patient survival after transplantation was 74.4% and those for HCV(-) and HCV(+) recipients were 81.3% and 66.6%, respectively (P = .46). The overall 6-year actuarial graft survival was 63.9% and those for HCV(+) and HCV(-) recipients were 68.8% and 57.1%, respectively (P = .6). CONCLUSION: We conclude that HBcAb(+) liver grafts can be used for both HCV(+) patients and HCV(-) patients who are critically ill, have early hepatocellular carcinoma, or have been exposed to HBV in the past. A short course of HBIg-lamivudine combination therapy provides effective prophylaxis against HBV infection in 89% of recipients of HBcAb(+) grafts.     

Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation

BACKGROUND: The use of hepatitis B core antibody (HBcAb+) and hepatitis C antibody (HCV Ab+) positive donors represents one strategy to increase available donor organs, but this remains controversial because of concern for viral transmission to recipients. We hypothesized that isolated HBcAb+ donors represent minimal risk of viral transmission in vaccinated lung transplant (LTx) recipients. METHODS: A retrospective study was performed of LTx recipients who received HBcAb+ or HCV Ab+ pulmonary allografts. We analyzed liver function studies, viral hepatitis screening tests, quantitative polymerase chain reaction for hepatitis B viral DNA (HBV DNA) and hepatitis C viral RNA (HCV RNA), freedom from bronchiolitis obliterans syndrome, acute rejection, and survival. RESULTS: Between April 1992 and August 2003, 456 LTx operations were performed. Twenty-nine patients (HB group) received HBcAb+ allograft transplants with a median posttransplant follow-up of 24.5 months. Three critically ill patients (HC group) received HCV Ab+ allografts with a median follow-up of 21.5 months. One-year survival for the HB group is 83% versus 82% for all patients who received non-HB organs (P=0.36). No patient in the HB group developed clinical liver disease because of viral hepatitis, and all patients alive (n=21) at follow-up are, to date, HBV DNA and/or HBcAb negative. All patients in the HC group tested HCV RNA positive; one patient died of liver failure at 22 months. CONCLUSIONS: Risk of viral transmission with HCV Ab+ allografts seems high after LTx. However, the use of HBcAb+ pulmonary allografts in recipients with prior hepatitis B vaccination seems to be a safe and effective strategy to increase organ availability.     

Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage

While the number of cadaveric organ donors remains relatively stable, the number of patients awaiting transplantation continues to increase, creating a shortage of donor organs. To address this imbalance, there is interest in transplanting organs formerly considered marginal or undesirable. Thus, more organs are currently transplanted from living donors, older donors, hemodynamically unstable donors, non-heart-beating donors and donors with markers of prior hepatitis B virus (HBV) infection. A large number (up to 93.8%) of liver transplant seronegative recipients from anti-HBc antibody positive donors have acquired HBsAg after liver transplantation in the absence of immunoprophylaxis. Based on experience in liver transplantation programs, transmission of HBV from donors without HBsAg but with antibody to HBV core antigen (anti-HBc), although conventionally defined as evidence of resolved infection, can have adverse consequences on both graft and recipient. On the contrary, HBV appears to be in-frequently transmitted from HBsAg negative/anti-HBcAb positive kidney donors: the incidence of de novo HBsAg seropositivity after renal transplantation ranges between 0 and 5.2%. A significantly higher incidence of anti-HBc antibody seroconversion (without developing HBsAg) after renal transplantation with anti-HBc antibody positive donors was seen. However, anti-HBc antibody positive renal allografts should be considered, especially for recipients who have been successfully immunized with HBV vaccine. Prospective long-term studies are in progress to assess the risk of de novo HBV infection (HBsAg seroconversion) in renal transplant recipients who have not been successfully immunized with vaccine against HBV.     

Safe use of livers from donors with positive hepatitis B core antibody

Thirty-five patients received liver transplants using liver donors who had positive test results for the hepatitis B core antibody (HBcAb). In the same time frame, 195 patients received HBcAb-negative liver donors. Mean follow up for patients receiving HBcAb-positive donors was 25 months. All patients receiving HBcAb-positive donors were monitored for recurrence of hepatitis B (HBV) with HBV DNA assays. There was no de novo HBV in recipients of HBcAb-negative grafts. In the group of patients receiving HBcAb-positive donors, 4 of 35 patients died within 3 months after transplant with no evidence of HBV recurrence at time of death. Four patients were transplanted for HBV-related disease and were postoperatively placed on lamivudine and hepatitis B immune globulin (HBIG). HBV recurrence was seen in one of these patients. Of the remaining 27 patients, three of three mismatched patients (HBcAb-positive donor to HBcAb-negative recipient) developed de novo HBV (100%). Of 24 matched patients (HBcAb-positive donor to HBcAb-positive recipient), only two (7%) developed recurrent HBV allograft reinfection. All de novo and recurrent HBV infections were successfully managed with HBIG and lamivudine therapy. Survival for this subgroup of patients receiving HBcAb-positive donors for non-HBV–related liver disease was 100%. We conclude that the judicious use of HBcAb-positive donors is reasonably safe and associated with low morbidity and mortality, with the appropriate follow-up protocols. Additionally, lamivudine use can be reserved for those cases with de novo or recurrent HBV in the liver allograft, or, selectively, as prophylaxis in those recipients patients who are naı&#x0308;ve to HBV and receive an HBcAb-positive donor. (Liver Transpl 2002;8:556-561.)     

Long-term results of treatment of chronic hepatitis B, C and D with interferon-α in renal allograft recipients

Abstract The aim of this study was to evaluate the efficacy and safety of interferon-a (IFN-α) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-α three times weekly for 6 months. After IFN-α therapy, 18 patients (43 %) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-α therapy. Repeated liver biopsy was performed in 16 patients after 6–24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-α therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-α therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0–84 months). IFN-α seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.     

儿童活体肝移植受者术后新发乙型肝炎病毒感染的临床研究

目的  探讨儿童活体肝移植术后新发乙型肝炎病毒(HBV)感染的临床特点及其防治策略。方法  2010年7月至2014年7月, 在首都医科大学附属北京友谊医院移植中心和天津一中心医院器官移植中心接受活体肝移植术的106例儿童受者纳入本研究, 所有手术由同一外科团队完成。根据供者术前HBV血清学标志物的结果, 将儿童受者分为供肝乙型肝炎核心抗体(抗-HBc)阳性组(45例)和供肝抗-HBc阴性组(61例)。了解两组儿童受者的新发HBV感染情况, 分析供肝抗-HBc阳性组儿童受者新发HBV感染的危险因素, 了解新发HBV感染患儿的特征。结果  供肝抗-HBc阳性组和阴性组新发HBV感染发生率分别为18%(8/45)和2%(1/61)。受者术前抗-HBs阴性、术后无抗病毒治疗是抗-HBc阳性供肝受者新发HBV感染的危险因素(均为P < 0.05)。发病距移植手术的中位数时间12个月(8~48个月)。9例儿童受者中, 接受拉米夫定治疗7例, 未予抗病毒治疗2例, 均全部存活。结论  应用抗-HBc阳性供肝的儿童肝移植受者, 其术后存在感染HBV的风险。受者术前抗-HBs阴性、术后未给予预防性核苷类似物治疗是抗-HBc阳性供肝受者新发HBV感染的危险因素。接受供体抗-HBc阳性的肝移植儿童受体应使用核苷类似物预防新发HBV感染, 移植术前亦要加强对其接种乙肝疫苗。     

Liver transplantation for chronic viral hepatitis

A better understanding of the mechanism of viral replication and of viral transmission has led to improved results with OLTx for patients with end-stage liver disease caused by viral hepatitis. Patients with hepatitis-B-related liver disease who are HBV-DNA negative can expect excellent survival after OLTx with long-term HBIG therapy. Patients coinfected with HDV who are HBV-DNA negative can also expect an excellent rate of survival. HBV-DNA-positive patients may benefit from the addition of lamivudine to the prophylactic regimen both before and after OLTx. De novo HBV infections generally have a very benign course. Lamivudine has proven to be very effective in the treatment of both de novo and recurrent HBV infection after OLTx; however, resistance can develop. Allografts from donors with antibodies to HBV can be used most effectively when directed to recipients who also harbor HBV antibodies. The recurrence of HCV infection after OLTx is universal; however, the 5-year survival rate in patients who received OLTx for HCV-related liver disease is not diminished. Although a few patients experience an aggressive recurrence of HCV infection after OLTx, prognostic indicators have not been determined to allow for identification of these patients. Alpha-interferon does not seem to be effective in the treatment of recurrent HCV infection after OLTx. Trials with combination alpha-interferon-ribavirin are underway. Retransplantation for HCV-related allograft failure can be performed safely in patients if performed before the onset of other organ system failure. Finally, anti-HCV-positive recipients of allografts from anti-HCV-positive donors have an excellent 5-year survival rate.