Victor Araya

Infectivity of hepatic allografts with antibodies to hepatitis B virus

BACKGROUND Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.

Long-term outcome of controlled, non-heart-beating donor liver transplantation.

Background. Previous reports have established the feasibility of using livers from controlled, non–heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. Methods. Retrospective database review for the last 7 years (1995–2002), encompassing 19 patients receiving CNHBD, with follow-up period of 1,000±694 days, median 762 days. Detailed review of recipient characteristics, operative and clinical course, immunosuppression, complications, survival rates, and comparison with the results obtained in patients receiving transplants of allografts procured in standard fashion, from heart-beating donors Results. Kaplan-Meier patient survival rates were 100%, 89.5%, and 83.5% at 30 days, 1, and 2 years, respectively, which is not different from recipients of livers procured from heart-beating cadaveric donors (P=0.74, log-rank test). Five patients died at a mean follow-up time of 492 (range 46–1,103) days. The causes of death were related to secondary sclerosing cholangitis (n=1), cardiac failure (n=1), and sepsis (n=3). Two (10.5%) recipients underwent retransplantation, one for primary graft nonfunction and one because of biliary cast syndrome with cholangitis. Significant preservation damage (ALT>2,000) developed in five patients, but this did not affect survival. The incidence of vascular (15.6% vs. 9.6%, P=0.34) and biliary complications (10.55 vs. 13.8%, P=0.68) was no different than for those recipients receiving standard cadaveric donors. Conclusions. CNHBD safely expands the donor pool with similar long-term results as those obtained in patients receiving organs from brain-dead donors under standard procurement techniques.

Impact of weight-based ribavirin with peginterferon alfa-2b in african americans with hepatitis C virus genotype 1

WIN‐R (Weight‐based dosing of pegINterferon alfa‐2b and Ribavirin) was a multicenter, randomized, open‐label, investigator‐initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG‐IFN) alfa‐2b plus a flat or weight‐based dose of ribavirin (RBV) in treatment‐naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG‐IFN alfa‐2b at 1.5 μg/kg/week plus flat‐dose (800 mg/day) or weight‐based‐dose RBV (800 mg/day for weight <65 kg, 1000 mg/day for 65‐85 kg, 1200 mg/day for >85‐105 kg, or 1400 mg/day for >105‐<125 kg). Sustained virologic response (SVR; undetectable [<125 IU/mL] hepatitis C virus [HCV] RNA at end of follow‐up) in patients ≥65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN‐R was conducted to evaluate the efficacy of weight‐based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight‐based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight‐based‐dose group than in the flat‐dose group. Safety and rates of drug discontinuation were similar between the 2 groups. Conclusion: Weight‐based dosing of RBV is more effective than flat dosing in combination with PEG‐IFN alfa‐2b in African American individuals with HCV genotype 1. Even with weight‐based dosing, response rates in African American individuals are lower than reported in other ethnic groups. (HEPATOLOGY 2007.)

Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation.

Background. Hepatitis C virus (HCV)-related cirrhosis is the leading indication for orthotopic liver transplantation (OLTx). HCV recurrence is universal after OLTx, with a highly variable course. This study aimed to find factors that affect progression of fibrosis in recurrent HCV. Methods. Fifty-eight HCV patients underwent OLTx at our center who were selected on the basis of available preOLTx serum or explanted liver sample and liver biopsy obtained at least 6 months postOLTx. All liver biopsies were performed when clinically indicated and were scored using the modified Hepatitis Activity Index (HAI). Primary immunosuppression consisted of tacrolimus and prednisone. Results. The group included 41 males (mean age 49.6 years). HCV genotype distribution was 1a, 31 (53%); 1b, 16 (28%), and others 11 (19%). The mean follow-up was 53.1 months. Patients with genotype 1a (n=31; mean 46.3 months) had significantly lower fibrosis-free survival analyzed by the presence of fibrosis stages 5 and 6 when compared with other genotypes (n=27; mean 60.1 months; P =0.0088, log rank test). Mean HAI scores were significantly higher in HCV genotype 1a, although there were no differences in survival between genotypes. Similarly, patients with cytomegalovirus (CMV) infection postOLTx (n=4) had a higher fibrosis progression rate compared with those without CMV (n=54) (mean fibrosis-free survival 29.0 vs. 53.0 months P =0.0004, log-rank test). Human leukocyte antigen matching and rate of acute rejection did not influence progression of fibrosis. Conclusion. Patients with HCV genotype 1a and those developing CMV postOLTx have a higher rate of hepatic fibrosis progression after OLTx for HCV-related chronic liver disease.

Operative Start Times and Complications After Liver Transplantation

The recent national focus on patient safety has led to a re‐examination of the risks and benefits of nighttime surgery. In liver transplantation, the hypothetical risks of nighttime operation must be weighed against either the well‐established risks of prolonging cold ischemia or the potential risks of strategies to manipulate operative start times. A retrospective review was conducted of 578 liver transplants performed at a single institution between 1995 and 2008 to determine whether the incidence of postoperative complications correlated with operative start times. We hypothesized that no correlation would be observed between complication rates and operative start times. No consistent trends in relative risk of postoperative wound, vascular, biliary, or other complications were observed when eight 3‐h time strata were compared. When two 12‐h time strata (night, 3 p.m.–3 a.m., and day, 3 a.m.–3 p.m.) were compared, complications were not significantly different, but nighttime operations were longer in duration, and were associated a twofold greater risk of early death compared to daytime operations (adjusted OR 2.9, 95% CI 1.16–7.00, p = 0.023), though long‐term survival did not differ significantly between the subgroups. This observation warrants further evaluation and underscores the need to explore and identify institution‐specific practices that ensure safe operations regardless of time of day.

The role of hepatitis E virus infection in adult Americans with acute liver failure

Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV‐related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti‐HEV immunoglobulin (Ig) M and anti‐HEV IgG levels. Subjects with a detectable anti‐HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug‐induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy‐related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti‐HEV IgM, but all were HEV‐RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36‐year‐old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti‐HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti‐HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3‐week survival compared to anti‐HEV IgG‐ subjects (63% vs. 70%; P = 0.018). Conclusion: Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy‐related ALF cases. Past exposure to HEV with detectable anti‐HEV IgG was significantly more common in the ALF patients compared to the general U.S. population. (Hepatology 2016;64:1870‐1880)

MELD score less than 15 predicts prolonged survival after transjugular intrahepatic portosystemic shunt for refractory ascites after liver transplantation.

Background. Transjugular intrahepatic portosystemic shunt (TIPS) is used in the management of refractory ascites (RA) and variceal bleeds. Little data exist on TIPS safety, efficacy, and survival after liver transplantation (LT). Methods. We conducted a retrospective analysis of patients who underwent TIPS placement after LT for RA. Clinical success was defined as a reduction of portosystemic gradient (PSG) and resolution of RA. Results. Twenty-six patients underwent TIPS. The most common indication for LT was hepatitis C virus (88%). Median time from LT to TIPS was 17 months (1–89 months). Median pre-TIPS model for end-stage liver disease (MELD) score was 15 (7–33). The median pre-TIPS PSG was 18 mm Hg (7–38 mm Hg). Median change in the PSG after TIPS was 11 mm Hg (1–27 mm Hg). Fifty-eight percent (15/26) of TIPS were considered clinically successful. Median post-TIPS patient survival was 15 months (1–109 months). Cumulative 1-year post-TIPS patient survival was 50%. On multivariate analysis, pre-TIPS MELD was a significant and independent predictor of patient survival (P<0.01). The 3- and 6-month patient mortality and graft loss for patients with a pre-TIPS MELD of more than or equal to 15 were significantly higher than those with a pre-TIPS MELD score of less than 15 (P<0.01). The overall median survival for patients with a pre-TIPS MELD score of more than or equal to 15 was 3 months (1–59 months) compared with 45 months (2–109 months) for patients with pre-TIPS MELD score of less than 15. Conclusions. TIPS after LT can be clinically effective in patients with RA with a MELD score less than 15. This suggests that TIPS could be used as a means to extend posttransplant survival but should be carefully individualized in patients with a MELD score more than or equal to 15.

Vascular Steal of the Portal Vein After Orthotopic Liver Transplant Intraoperative Sonographic Diagnosis

Spontaneous splenorenal shunts (SSRSs) are portosystemic connections between the splenic vein and the left renal vein (LRV) that develop commonly in patients with portal hypertension. 1 They reportedly occur in 18% to 19% of patients evaluated for a liver transplant. 2, 3 As the liver become more cirrhotic, a major steal phenomenon may occur, whereby blood is shunted from the high‐resistance venous bed of the liver to the lower systemic pressure of the LRV. 4 Not infrequently, an SSRS will go undetected during orthotopic liver transplantation because dissection is limited to the right upper quadrant.

Guillain-Barre syndrome associated with peginterferon alfa- 2a for chronic hepatitis C: A case report

The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bells Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection.

Falsely Elevated Tacrolimus Levels Caused by Immunoassay Interference Secondary to β-Galactosidase Antibodies in an Infected Liver Transplant Recipient

Careful interpretation of tacrolimus levels is essential to ensure optimal immunosuppressive therapy while avoiding toxicity. Interference with tacrolimus assays may be an underreported event that has the potential to result in negative patient outcomes through unnecessary modifications of therapy. We describe a 55–year‐old liver transplant recipient who had falsely elevated tacrolimus levels that led to the eventual disruption of his immunosuppressive therapy and subsequent rejection of his allograft. Although his increased tacrolimus levels did not correlate with clinical signs and symptoms of tacrolimus toxicity, interruption of therapy in this patient was supported by an acute infection and a slight elevation in serum creatinine concentration. Tacrolimus levels were analyzed by using an antibody conjugated magnetic immunoassay method, and levels as high as 79.7 ng/ml were observed, despite discontinuation of tacrolimus. We conducted an evaluation for assay interference by using an alternative assay method (microparticle enzyme immunoassay), by testing plasma samples that were not hemolyzed, and by analyzing levels of an unrelated drug that uses the same technology as the initial tacrolimus assay. β‐Galactosidase antibodies were ultimately confirmed as the cause of the immunoassay interference. In patients receiving tacrolimus, spuriously high tacrolimus levels should be carefully evaluated, and drastic adjustments to therapy should be made only within the context of clinical toxicity.