Human serum N-glycome profiling via the newly developed asparagine immobilized cellulose/polymer nanohybrid.

Human serum N-linked glycans expression levels change during the disease progression. The low abundance, structural diversity, and coexisting matrices hinder their detection in mass spectrometry analysis. Considering the hydrophilic nature of N-glycans, cellulose/polymer (1,2-Epoxy-5-hexene) nanohybrid is fabricated with oxirane groups functionalized of asparagine to develop solid phase extraction based hydrophilic interaction liquid chromatography sorbent (cellulose/1,2-Epoxy-5-hexene/asparagine). The morphology, elemental analysis, and surface properties are studied through scanning electron microscopy, energy dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The large surface area of cellulose/polymer nanohybrid (2.09 × 102  m2 /g) facilitates the high density of asparagine immobilization resulting in better hydrophilic interaction liquid chromatography enrichment under optimized conditions. The enrichment capability of nanohybrid/asparagine is assessed by the N-Linked glycans released from ovalbumin and immunoglobulin G where 23 and 13 N-glycans are detected respectively. The nanohybrid/asparagine shows selectivity of 1:1200 with spiked bovine serum albumin and sensitivity down to 100 attomole. Human serum profiling for N-glycans identifies 52 glycan structures. This new enrichment strategy enriches serum N-linked glycans in the presence of salts, proteins, endogenous serum peptides, and so forth.

Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A Systematic Review and Meta-Analysis.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Safety and efficacy of antibiotics among acutely decompensated cirrhosis patients.

BACKGROUND AND AIM: Infection is a leading precipitant of acute-on-chronic liver failure. This study aims to determine the safety and efficacy of antibiotics within acute-on-chronic liver failure. METHODS: Retrospective study of 457 acute-on-chronic liver failure patients admitted to the University of Arizona Health Network between January 1 and December 31, 2014. Eligibility criteria were as follows: at least 18 years of age and 6 months follow-up, data available to calculate systemic inflammatory response syndrome (SIRS), and acute-on-chronic liver failure. This study collected patient's clinical features and historical data. Key data points were infection, antibiotic use, and SIRS. This study used Cox proportional hazards to model the effects of clinical factors on risk of death. RESULTS: A total of 521 of 1243 met the inclusion criteria, and 64 had missing data, leaving 457 patients. Infection resulted in higher hazard (hazard ratio [HR] = 1.6, confidence interval [CI]: 1.1-1.3, P = 0.01). Patients with infections and antibiotics, compared with non-infected patients without antibiotics, had higher hazard (HR = 1.633, CI: 1.022-2.609, P = .04). Of those infected patients with antibiotics, SIRS patients experienced higher hazard (HR = 1.9, CI: 1.1-3.0, P = .007). Multivariable Cox proportional hazards associated the following with higher hazard: SIRS (HR = 1.866, CI: 1.242-2.804, P = 0.003), vancomycin (HR = 1.640, CI: 1.119-2.405, P = 0.011), Model for End-Stage Liver Disease (HR = 1.051, CI: 1.030-1.073, P < 0.001), gastrointestinal bleeding (HR = 1.727, CI: 1.180-2.527, P = 0.005), and hepatic encephalopathy (HR = 1.807, CI: 1.247-2.618, P = 0.002). CONCLUSION: Overall, treatment of infection with antibiotics did not improve survival; however, patients not meeting SIRS criteria had better outcomes, and vancomycin was associated with poorer survival among acute-on-chronic liver failure patients.

Pyridoxine Deficiency After Solid Organ Transplant.

OBJECTIVE: Pyridoxine is 1 of 8 B vitamins that assist in a variety of essential functions including immune functions. The purpose of this study was to assess the risk factors associated with low pyridoxine levels in solid organ transplantation recipients. DESIGN: The study cohort was divided into 2 groups: (a) patients with normal pyridoxine levels or (b) patients with low pyridoxine levels. Dietary evaluation and clinical characteristics of all patients, rejection episodes, and immunosuppression were collected. Simple descriptive statistics were used to analyze the overall cohort. RESULTS: Of the 48 patients, 29 (60%) in the study cohort were identified to have low pyridoxine levels. The mean interval between transplantation and pyridoxine level check was 910 days (standard deviation [SD] 456). The mean weight at the time of dietary consultation was 80 kg (SD 20.7). More patients in the deficient group received thymoglobulin for rejection treatment (56% vs 0%; P = .01) and were thymoglobulin recipients (78% vs 10%; odds ratio [OR] = 31.5; 95% confidence interval [CI], 2.35-422.30; P < .01). A strong correlation was identified between thymoglobulin treatment for induction and a low level of pyridoxine (correlation coefficient R = 0.6, P = .004) and between thymoglobulin treatment for rejection and a low pyridoxine level (correlation coefficient R = 0.5, P = .05). Based on multivariate logistic regression analysis, only thymoglobulin treatment (induction or rejection treatment) was significantly associated with low pyridoxine levels (OR = 19.5, 95% CI, 1.01-375.24; P < .05). CONCLUSIONS: Low levels of pyridoxine appear to be relatively common, and thymoglobulin treatments are associated with low pyridoxine levels. Prospective studies are needed to confirm and valuate the significance of these findings.

Big spleens and hypersplenism: fix it or forget it?

Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.

Early liver retransplantation in adults.

Up to 23% of liver allografts fail post-transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high-risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49,288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0-7), month (20%, day 8-30), and year (33%, day 31-365). Only retransplantation within the first year (day 0-365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high-risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation.

Correlation of 13C urea breath test values with Helicobacter pylori load among positive patients.

BACKGROUND/AIMS: 13C urea breath test (13C UBT) is used to detect Helicbacter (H.) pylori in gastric mucosa. There are controversial results regarding associations of 13C UBT values with histopathological grades. We designed this study to correlate 13C UBT values with different histopathological grades in our local setting. METHODOLOGY: 13CO2/12CO2 ratio for 13C UBT was analyzed using mass spectrometry and histopatholgical grades were scored by updated Sydney System. RESULTS: 13C UBT values of H. pylori positive patients at different times (T10-T60) were higher as compared to negative patients. Significant positive correlation of 13C UBT values at T30 with different scores of H. pylori load (r = 0.277, p = 0.037) was observed. Associations of the mean 13C UBT values with neutrophil infiltration (p = 0.214), mononuclear cell infiltration (p = 0.648), atrophy (p= 0.620), atypia (p = 0.057) and metaplasia scores (p = 0.718) were found to be nonsignificant. H. pylori load significantly correlated with neutrophil infiltration and atrophy with exception of mononuclear cell infiltration, atypia and metaplasia. CONCLUSIONS: In the present analysis, significant positive correlation was observed between 13C UBT values and H. pylori load that would be helpful in qauntification of H. pylori in our local setting.

Metabolic dysfunction-associated steatotic liver disease heterogeneity: Need of subtyping.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread global disease with significant health burden. Unhealthy lifestyle, obesity, diabetes mellitus (DM), insulin resistance, and genetics have been implicated in the pathogenesis of MASLD. A significant degree of heterogeneity exists among each of above-mentioned risk factors. Heterogeneity of these risk factors translates into the heterogeneity of MASLD. On the other hand, MASLD can itself lead to insulin resistance and DM. Such heterogeneity makes it difficult to assess the natural course of an individual with MASLD in clinical practice. At present MASLD is considered as one disease despite the variability of etiopathogenic processes, and we lack the consensus definitions of unique subtypes of MASLD. In this review, pathogenic processes of MASLD are discussed and a need of subtyping is recommended.

The survival outcomes following liver transplantation (SOFT) score: validation with contemporaneous data and stratification of high-risk cohorts.

Models to project survival after liver transplantation are important to optimize outcomes. We introduced the survival outcomes following liver transplantation (SOFT) score in 2008 (1) and designed to predict survival in liver recipients at three months post-transplant with a C statistic of 0.70. Our objective was to validate the SOFT score, with more contemporaneous data from the OPTN database. We also applied the SOFT score to cohorts of the sickest transplant candidates and the poorest-quality allografts. Analysis included 21 949 patients transplanted from August 1, 2006, to October 1, 2010. Kaplan-Meier survival functions were used for time-to-event analysis. Model discrimination was assessed using the area under the receiver operating characteristic (ROC) curve. We validated the SOFT score in this cohort of 21 949 liver recipients. The C statistic was 0.70 (CI 0.68-0.71), identical to the original analysis. When applied to cohorts of high-risk recipients and poor-quality donor allografts, the SOFT score projected survival with a C statistic between 0.65 and 0.74. In this study, a validated SOFT score was informative among cohorts of the sickest transplant candidates and the poorest-quality allografts.

A critical analysis of early death after adult liver transplants.

INTRODUCTION: The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. METHODS: We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. RESULTS: The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). CONCLUSION: We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality.

The Impact of Metabolic Syndrome on the Prognosis of High-Risk Alcoholic Hepatitis Patients: Redefining Alcoholic Hepatitis.

Background: Alcoholic hepatitis (AH) is characterized by acute symptomatic hepatitis associated with heavy alcohol use. This study was designed to assess the impact of metabolic syndrome on high-risk patients with AH with discriminant function (DF) score ≥ 32 and its effect on mortality. Methods: We searched the hospital database for ICD-9 diagnosis codes of acute AH, alcoholic liver cirrhosis, and alcoholic liver damage. The entire cohort was categorized into two groups: AH and AH with metabolic syndrome. The effect of metabolic syndrome on mortality was evaluated. Also, an exploratory analysis was used to create a novel risk measure score to assess mortality. Results: A large proportion (75.5%) of the patients identified in the database who had been treated as AH had other etiologies and did not meet the American College of Gastroenterology (ACG)-defined diagnosis of acute AH, thus had been misdiagnosed as AH. Such patients were excluded from analysis. The mean body mass index (BMI), hemoglobin (Hb), hematocrit (HCT), and alcoholic liver disease/non-alcoholic fatty liver disease index (ANI) were significantly different between two groups (P < 0.05). The results of a univariate Cox regression model showed that age, BMI, white blood cells (WBCs), creatinine (Cr), international normalized ratio (INR), prothrombin time (PT), albumin levels, albumin < 3.5, total bilirubin, Na, Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), MELD ≥ 21, MELD ≥ 18, DF score, and DF ≥ 32 had a significant effect on mortality. Patients with a MELD greater than 21 had a hazard ratio (HR) (95% confidence interval (CI) of 5.81 (2.74 - 12.30) (P < 0.001). The adjusted Cox regression model results showed that age, Hb, Cr, INR, Na, MELD score, DF score, and metabolic syndrome were independently associated with high patient mortality. However, the increase in BMI and mean corpuscular volume (MCV) and sodium significantly reduced the risk of death. We found that a model including age, MELD ≥ 21, and albumin < 3.5 was the best model in identifying patient mortality. Our study showed that patients admitted with a diagnosis of alcoholic liver disease with metabolic syndrome had an increased mortality risk compared to patients without metabolic syndrome, in high-risk patients with DF ≥ 32 and MELD ≥ 21. A bivariate correlation analysis revealed that patients with AH with metabolic syndrome were more likely to have infection (43%) compared to AH (26%) with correlation coefficient of 0.176 (P = 0.03, CI: 0.018 - 1.0). Conclusion: In clinical practice, the diagnosis of AH is inaccurately applied. Metabolic syndrome significantly increases the mortality risk in high-risk AH. It signifies that the presence of features of metabolic syndrome modifies the behavior of AH in acute settings, warranting different therapeutic strategies. We propose that in defining AH, patients overlapping with metabolic syndrome may need to be excluded as their outcome is different with regard to risk of renal dysfunctions, infections and death.

Fungal Infection in Acutely Decompensated Cirrhosis Patients: Value of Model for End-Stage Liver Disease Score.

BACKGROUND: Infection in acute-on-chronic liver failure (ACLF) patients is known to cause higher mortality. The current approach is to culture all patient samples. There are no published data evaluating fungal infections in acutely decompensated patients. In this study, we aim to identify clinical factors predictive of infections within ACLF patients and assess workup compliance within 24 h of hospital admission. METHODS: We retrospectively analyzed the charts of 457 ACLF patients seen at the University of Arizona between January 1, 2014 and December 31, 2014. We used logistic regression to identify potential risk indicators for bacterial, fungal, and any infections. In order to proceed to a systemic infection workup, the following parameters were assessed: complete blood count, urinalysis, urine culture, bacterial blood culture, chest X-ray, and ascitic fluid analysis in patients with ascites. Additionally, serological markers were also assessed in patient samples. Systemic inflammatory response syndrome (SIRS) was defined as the presence of two or more of the following criteria: temperature > 38 °C or < 36 °C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min, white blood cell count > 12,000 or < 4,000 cells/mm or > 10% bands. RESULTS: An established infection was observed in 60.61% of ACLF patients. SIRS criteria predicted infections with concordance statistic (C-statistic) of 0.71 (odds ratio (OR) 6.85, 95% confidence interval (CI): 4.33, 10.85) for any infection, 0.63 (OR 2.88, 95% CI: 1.96, 4.23) for bacterial infection, and 0.53 (OR 1.32, 95% CI: 0.59, 2.96) for fungal infection. After including other significant variables (over 10 additional variables), predictive ability improved, C-statistic 0.83 (95% CI: 0.77, 0.90) for any infection and 0.71 (95% CI: 0.65, 0.77) for bacterial infections. The combination of model for end-stage liver disease (MELD) and hemoglobin (Hb) predicted fungal infections with C-statistic 0.74 (95% CI: 0.63, 0.84). Workup within 24 h of admission was obtained in 12% of patients. CONCLUSIONS: Fungal infections in ACLF patients results in an increased mortality rate. Elevated MELD and low Hb in combination predict fungal infections. Compliance is very poor to obtain diagnostic workup efficiently, better tools are needed to predict infection upon admission.

Efficacy of Low Dose Chemoprophylaxis for Coccidioidomycosis Infection in Liver Transplant Recipients.

BACKGROUND: Coccidioidomycosis (CM) infections among transplant recipients result in significant morbidity and mortality. The goal of our study was to establish the efficacy of low dose (LD) versus standard dose (LD, 50 mg daily) fluconazole in preventing CM infection. METHODS: This was a retrospective study utilizing electronic medical records of liver transplant recipients at the University of Arizona. The primary end point was post-transplant CM status, such as infection, complications and survival. RESULTS: We detected a statistically significant correlation between positive pre-transplant status and positive post-transplant status (hazards ratio: 8.25 (95% confidence interval: 1.028 - 66.192)). There was a trend towards improved survival in patients who had a positive post-transplant CM status in the SD group versus LD group (90.9% versus 81.3%), although not statistically significant. CONCLUSION: The risk of CM infection among transplant recipients in the absence of prophylaxis is associated with high morbidity and mortality. We currently use SD fluconazole as universal prophylaxis in all transplant recipients despite not establishing statistical significance between LD and SD. We believe that the survival trend detected may have not reached statistical significance due to low power impact. Since the standardization of SD prophylaxis at our institution, we have not diagnosed further new post-transplant CM infections.

Oral aloe vera-induced hepatitis.

OBJECTIVE: To report a case of possible oral aloe vera-induced hepatitis. CASE SUMMARY: A 73-year-old female was admitted to the hospital for acute hepatitis. Extensive laboratory testing did not reveal the cause of the patient's disease. She was asked multiple times whether she was taking any home medications, which she initially denied. It was only after an extensive medication history done by a clinical pharmacist that the patient admitted to using oral aloe vera capsules for constipation. Upon discontinuation of the oral aloe vera, liver markers of hepatotoxicity returned to normal levels. DISCUSSION: Herbal medications pose an increasing problem in patient safety, as the different types of these products and the number of patients who use them continue to grow. In the US, these products are not subject to the same regulatory scrutiny as prescription medications; thus, safety information can be difficult to obtain. In particular, hepatic toxicity due to herbal agents is poorly described in the medical literature. Aloe vera, often used topically for minor burns, can also be used orally as a laxative or an "anti-aging" agent. According to the Naranjo probability scale, the hepatotoxicity in this case was possibly related to ingestion of oral aloe vera. Additionally, using the Roussel Uclaf Causality Assessment Method for determining drug hepatotoxicity, the patient's symptoms were scored as probably caused by oral aloe vera. The more conservative designation was used in our report. CONCLUSIONS: With the widespread use of oral aloe vera and other herbal products, clinicians faced with a case of acute hepatitis that is not readily diagnosed should question patients about herbal use.

Drug-Induced Acute Liver Failure.

Drug-induced acute liver failure (ALF) disproportionately affects women and nonwhites. It is most frequently caused by antimicrobials and to a lesser extent by complementary and alternative medications, antiepileptics, antimetabolites, nonsteroidals, and statins. Most drug-induced liver injury ALF patients have hepatocellular injury pattern. Cerebral edema and intracranial hypertension are the most serious complications of ALF. Other complications include coagulopathy, sepsis, metabolic derangements, and renal, circulatory, and respiratory dysfunction. Although advances in intensive care have improved outcome, ALF has significant mortality without liver transplantation. Liver-assist devices may provide a bridge to transplant or to spontaneous recovery.

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation.

BACKGROUND: We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. METHODS: Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. RESULTS: Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. CONCLUSIONS: SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated.

Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment.

BACKGROUND: The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. METHODS: The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. RESULTS: The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. CONCLUSIONS: In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival.

Hepatitis C in Liver Allograft Recipients: Utility of One-Year Post-Transplantation Biopsy as an Indicator of Antiviral Therapy.

BACKGROUND: All-oral interferon-free regimens for hepatitis C viral (HCV) infection are highly efficacious; however, high cost is a barrier to applicability. Liver allograft recipients are particularly likely to benefit from therapy as HCV often leads to graft dysfunction and loss. In this study, we aimed to establish the utility of allograft biopsy at 1 year post-transplant as an indicator of treatment. METHODS AND RESULTS: Among 252 liver recipients enrolled, 136 (54%) developed severe disease (fibrosing cholestatic hepatitis (FCH) or fibrosis stage ≥ 2 at 1 year post-transplant). Multivariable analysis revealed younger recipient age and female gender, older donor age and T cell depletive therapy to be independent predictors of severe disease. Recipients with severe disease had higher rate of further graft loss compared to those with mild disease. Patients with mild disease and sustained virologic response (SVR) had the best survival rate, whereas those with severe disease and viremia had the worst survival (96% versus 63% at 5 years). CONCLUSION: In conclusion, allograft biopsy at 1 year helps identify recipients at high risk of further graft dysfunction and loss. In view of high cost of therapy, treatment should be preferably directed to high-risk patients including those with FCH or fibrosis stage ≥ 2 by 1 year post-transplant.