Current status of liver transplantation for human immunodeficiency virus-infected patients in mainland China.

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Ambulatory end-stage liver disease in Ghana; patient profile and utility of alpha fetoprotein and aspartate aminotransferase: platelet ratio index.

BACKGROUND: End-stage liver disease (ESLD) is a major burden on public health, particularly in sub-Saharan Africa, where hepatitis B virus (HBV) is an important risk factor. We aimed to describe clinical characteristics of ESLD from cirrhosis or hepatocellular carcinoma (HCC) and the performance of aspartate aminotransferase (AST)-platelet ratio index (APRI) and alpha fetoprotein (AFP) in Ghana. METHODS: We performed an observational cross-sectional study in outpatient hepatology clinics at three teaching hospitals in Ghana, West Africa. One hundred and forty-one HCC, 216 cirrhosis and 218 chronic HBV patients were recruited by convenience sampling. Sociodemographic, history and examination, laboratory, and disease staging information were shown using descriptive statistics. Performance of the APRI score in diagnosis of cirrhosis and AFP in the diagnosis of HCC was determined using AUROC analysis. RESULTS: Median age at presentation was 44 years for HCC and 46 years for cirrhosis. HBV was found in 69.5% of HCC and 47.2% of cirrhosis cases, and HCV in 6.4% and 3.7% respectively. APRI cut-off of 2 had sensitivity of 45.4% and specificity of 95% in diagnosis of cirrhosis, and cut-off of 1 had sensitivity of 75.9% and specificity of 89%. AUC of AFP was 0.88 (95% CI 0.81-0.94) in diagnosis of HCC. Low monthly income was associated with lower odds of undertaking AFP. Thirty one percent of cirrhotic persons were Child-Pugh C, and 67.9% of HCC patients had advanced or terminal disease at presentation. CONCLUSIONS: Our findings emphasize the young age of ESLD patients in Ghana and the advanced nature at presentation. It highlights shortcomings in surveillance and the need for policies to address the burden and improve outcomes in Ghana.

Metabolomic Signature as a Predictor of Liver Disease Events in Patients With HIV/HCV Coinfection.

BACKGROUND: Advanced liver disease due to hepatitis C virus (HCV) is a leading cause of human immunodeficiency virus (HIV)-related morbidity and mortality. There remains a need to develop noninvasive predictors of clinical outcomes in persons with HIV/HCV coinfection. METHODS: We conducted a nested case-control study in 126 patients with HIV/HCV and utilized multiple quantitative metabolomic assays to identify a prognostic profile that predicts end-stage liver disease (ESLD) events including ascites, hepatic encephalopathy, hepatocellular carcinoma, esophageal variceal bleed, and spontaneous bacterial peritonitis. Each analyte class was included in predictive modeling, and area under the receiver operator characteristic curves (AUC) and accuracy were determined. RESULTS: The baseline model including demographic and clinical data had an AUC of 0.79. Three models (baseline plus amino acids, lipid metabolites, or all combined metabolites) had very good accuracy (AUC, 0.84-0.89) in differentiating patients at risk of developing an ESLD complication up to 2 years in advance. The all combined metabolites model had sensitivity 0.70, specificity 0.85, positive likelihood ratio 4.78, and negative likelihood ratio 0.35. CONCLUSIONS: We report that quantification of a novel set of metabolites may allow earlier identification of patients with HIV/HCV who have the greatest risk of developing ESLD clinical events.

Data linkage to monitor hepatitis C-associated end-stage liver disease and hepatocellular carcinoma inpatient stays in England.

Persons with chronic hepatitis C (HCV) infection are at increased risk of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). The impact of hepatitis treatment scale-up and elimination strategies on ESLD and HCC incidence is a critical measure of progress towards WHO targets. Data from national laboratory surveillance of HCV diagnoses were linked to inpatient care records in Hospital Episode Statistics (HES). For persons first diagnosed with HCV between 1998 and 2016, we describe the characteristics of those with ESLD and HCC and estimate incidence. Of persons diagnosed with HCV between 1998 and 2016 (104 674), 9.1% (9525) had an admission for ESLD and 2.5% (2610) for HCC. The majority of persons with ESLD and HCC were male (70.7% and 82.7%) and of white ethnicity (89.9% and 82.7%). Crude incidence of ESLD and HCC admission was 10.4 and 3.2 per 1000 person-years, respectively. When compared to 2011-2013, incidence of ESLD and HCC admissions in 2014-2017 were lower (ESLD incidence rate ratio [IRR]: 0.81; 95% Confidence interval [CI]: 0.76-0.86; HCC IRR: 0.90; 95% CI: 0.82-1.00, P = .045). Data linkage showed considerable underreporting of HCV in HES coding for ESLD and HCC (16.0% and 11.3%, respectively). In conclusion, we found a decline in incidence of ESLD and HCC-related inpatient admissions since 2011-2013. Linked analysis is required for the continued monitoring of ESLD and HCC inpatient incidence. However, HES data quality issues around completeness of identifiers contribute to uncertainty in linkage and may limit our ability to robustly monitor progress towards WHO elimination goals.

The Effect of Stem Cell Transplantation Therapy for Post Viral Chronic Liver Cell Failure on Associated Type II Diabetes Mellitus: A Pilot Study.

BACKGROUND: It was observed that type II diabetes mellitus associated with chronic liver failure improved after stem cell transplantation. However, there were no adequate studies regarding this issue. The aim of this study was to evaluate the effect of stem cell transplantation on associated type II diabetes mellitus and on the liver function tests. METHODS: This pilot study included 30 patients of post-hepatitis chronic liver failure who were classified into two groups: Group I included patients with chronic liver cell failure associated with type 2 diabetes. Group II included patients without type II diabetes. Autologous CD34+ and CD133+ stem cells were percutaneously infused into the portal vein. Responders (regarding the improvement of diabetes as well as improvement of liver condition) and non-responders were determined. Patients were followed up for one, three and six months after the intervention evaluating their three-hour glucose tolerance test, C- peptide (Fasting and postprandial), Child-Pugh score and performance score one month, three months, and six months after stem cell therapy. RESULTS: Both synthetic and excretory functions of the liver were improved in 10 patients (66.66 %) of group I and in 12 patients (80 %) of group II. Significant improvement in the Oral Glucose Tolerance Test in the responders of both the groups was well defined from the 3rd month and this was comparable to changes in liver function tests and Child-Pugh score. CONCLUSION: Successful stem cell therapy in chronic liver cell failure patients can improve but not cure the associating type 2 diabetes by improving insulin resistance.

Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease.

In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause of morbidity and mortality, resulting in death in 15-17% of human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated liver damage and promotes the progression to advanced fibrosis and cirrhosis. However, the mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation of HIV in hepatocytes, causing oxidative stress and intensive apoptotic cell death. Engulfment of HIV-containing apoptotic hepatocytes by non-parenchymal cells (NPCs) triggers their activation and liver injury progression. This study was performed on primary human hepatocytes and Huh7.5-CYP cells infected with HIV-1ADA, and major findings were confirmed by pilot data obtained on ethanol-fed HIV-injected chimeric mice with humanized livers. We demonstrated that ethanol exposure potentiates HIV accumulation in hepatocytes by suppressing HIV degradation by lysosomes and proteasomes. This leads to increased oxidative stress and hepatocyte apoptosis. Exposure of HIV-infected apoptotic hepatocytes to NPCs activates the inflammasome in macrophages and pro-fibrotic genes in hepatic stellate cells. We conclude that while HIV and ethanol metabolism-triggered apoptosis clears up HIV-infected hepatocytes, continued generation of HIV-expressing apoptotic bodies may be detrimental for progression of liver inflammation and fibrosis due to constant activation of NPCs.

Improved Graft Survival After Liver Transplantation for Recipients With Hepatitis C Virus in the Direct-Acting Antiviral Era.

Highly effective direct-acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer-term outcomes in HCV-positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single-organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV-positive liver transplant recipients who received either an HCV-negative or HCV-positive donor (donor [D]-/recipient [R]+; D+/R+) and HCV-negative liver transplant recipients who received a HCV-negative donor (D-/R-). The groups were further divided between the pre-DAA and DAA eras. There were 52,526 patients included: 31,193 were D-/R- patients; 18,746 were D-/R+ patients; and 2587 were D+/R+ patients. The number of D-/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D-/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End-Stage Liver Disease scores than those in the pre-DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV-positive recipients: D-/R+ 1-year survival was 92.4% versus 88.7% and 3-year survival was 83.7% versus 77.7% (DAA versus pre-DAA era, respectively) compared with D-/R- 1-year survival of 92.7% versus 91.0% and 3-year survival of 85.7% versus 84.0% (DAA versus pre-DAA era, respectively). The magnitude of improvement in 3-year graft survival was almost 4-fold greater for D-/R+ patients. The 3-year survival for D+/R+ patients was similar to HCV-negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one-third over the past decade. Graft survival among HCV-positive recipients has increased disproportionately in the DAA era with HCV-positive recipients now achieving similar outcomes to non-HCV recipients.

Survival and clinical events related to end-stage liver disease associated with HCV prior to the era of all oral direct-acting antiviral treatments.

Background: The aim of this study was to describe the natural long-term course of end-stage liver disease associated with chronic hepatitis C (HCV) infection by measuring survival and complication rates in the era prior to the arrival of new direct-acting antiviral (DAA) drugs. Methods: A retrospective population-based cohort study was designed to establish the follow-up of patients hospitalized for a decompensated cirrhotic event or hepatocellular carcinoma using electronic records from hospital discharge databases from 2009 to 2015. Their survival was compared with a sex, age and non-liver mortality excess matched simulation of the general Spanish population. Results: A total of 253 patients were included in the study. Among those with decompensated cirrhosis (n = 151) the hospital admission rate was 1.88 per patient-year with a mortality rate of 0.16 per patient-year. Mean survival was 4.10 years for patients with decompensated cirrhosis, and 1.75 for non-transplanted hepatocellular carcinoma, compared to 18.39 years for the general population. Conclusion: Our results show the complexity and rapid progression of end-stage liver disease associated with HCV infection. The considerable loss of life expectancy associated with the development of decompensated cirrhosis in patients with chronic HCV infection in the absence of viral clearance through treatment is acutely evident.

Liver decompensation in HIV/Hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono-infection.

BACKGROUND & AIMS: HIV/hepatitis B virus (HBV) coinfected subjects are thought to have faster progression to end-stage liver disease (ESLD) than HBV mono-infected subjects. We assessed whether this remains in the current cART-era. METHODS: Data from subjects with follow-up completion post-2003 were compared between HIV/HBV coinfected subjects in the Dutch HIV Monitoring database and HBV mono-infected subjects from two centres. The primary outcomes of composite ESLD included portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver-related mortality. Outcomes were analysed using time-dependent cause-specific Cox regression models adjusted for follow-up time and relevant covariates. Subset-analyses were done in subjects with follow-up pre-2003. RESULTS: In the 1336 co- vs 742 mono-infected subjects, coinfected subjects had no increased probability for ESLD compared to mono-infected subjects (cHR 0.7 (95% CI 0.4-1.1), but had increased probabilities for all-cause (cHR 7.4 [4.9-11.1]) and liver-related mortality (cHR 3.4 [1.6-7.5]). In the current combined cohort, treatment with tenofovir or entecavir was inversely associated with ESLD, all-cause and liver-related mortality (cHR 0.4 [95% CI 0.3-0.7], cHR 0.003 [0.001-0.01]), cHR 0.007 [0.001-0.05]). Other predictors for ESLD were older age, being of Sub-Sahara African descent, increased alanine aminotransferase levels and hepatitis C virus coinfection. While the probability for all-cause mortality was increased in coinfected subjects, this rate decreased compared to pre-2003 (HR 40.2 (95% CI: 8.7-186.2). CONCLUSIONS: HIV/HBV coinfected patients no longer seem to be at increased risk for progression to ESLD compared to HBV mono-infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity.

Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience.

BACKGROUND: Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS: Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS: HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS: Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.

Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co-infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End-Stage Liver Disease as Compared to HCV Mono-infected Patients.

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.

[Research progress in prognostic factors of hepatitis B virus-associated end-stage liver disease].

Hepatitis B remains a worldwide health problem with a high mortality rate associated with end-stage liver diseases. The Model for End-Stage Liver Disease and Child-Pugh score is still widely used as the prognostic model for liver cirrhosis and inflammatory reaction, B-type natriuretic peptide and portal vein thrombosis are independent risk factors. Many new models have been proposed for liver failure, including a new model HINAT ACLF. HINAT ACLF is better than its preceding models and increased neutrophil-to-lymphocyte ratio is a single factor to promote thyroid hormone, cholinesterase, and antiviral treatment response in this model. HBV DNA is frequently involved in the predictive model of liver cancer, but with widespread use of antiviral drugs, the value of its long-term prognostication has gradually reduced. Therefore, liver stiffness value instead of HBV DNA shows apparent advantages in mREACH-B. ALBI has good median survival prediction value for hepatocellular carcinoma patients. Alpha-fetoprotein and staging method, which is based on tumor number and size, are still independent risk factors for liver cancer.

On-Treatment Improvement of MELD Score Reduces Death and Hepatic Events in Patients With Hepatitis B-Related Cirrhosis.

OBJECTIVES: Antiviral treatment modifies the natural history of chronic hepatitis B (CHB)-related cirrhosis as reflected by improving Model for End-Stage Liver Disease (MELD) score over time. We evaluated the impact of on-treatment change of MELD score on clinical outcomes in patients with CHB-related cirrhosis. METHODS: Cirrhotic CHB patients who received entecavir and/or tenofovir disoproxil fumarate for at least 6 months in Hong Kong between 2005 and 2016 were identified. The primary outcome was all-cause mortality; secondary outcomes were hepatocellular carcinoma (HCC), and hepatic events including ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, hepatic encephalopathy, and liver transplantation. RESULTS: We identified 1743 cirrhotic CHB patients. Their mean MELD score decreased from 12.3 ± 5.5 at baseline to 11.0 ± 4.7 at month 6. At a median (interquartile range) follow-up of 3.9 (1.9-6.0) years, 290 (16.6%) patients died; 201 (11.5%) developed HCC. Among 1140 patients without prior hepatic events, 150 (13.2%) developed hepatic events. Among 464 patients with baseline MELD score ≥15, the 6-year cumulative mortality was 72.8, 36.7, and 23.1% for unchanged or increased MELD score, 1-5 point improvement in MELD score, and >5 point improvement in MELD score at month 6, respectively (log-rank test, P < 0.001); the corresponding 6-year cumulative incidence of hepatic events was 52.7, 30.5, and 23.9% in the three subgroups (Gray's test, P = 0.004). Patients with MELD score <15 at month 6 had lower risk of mortality and hepatic events (all P < 0.001). CONCLUSIONS: On-treatment improvement of MELD score correlates with reduced risk of mortality and hepatic events in cirrhotic CHB patients.

Sustained Virological Response Is Associated with a Decreased Risk of Posttransplant Diabetes Mellitus in Liver Transplant Recipients with Hepatitis C-Related Liver Disease.

Posttransplant diabetes mellitus (PTDM), an increasingly recognized complication of solid organ transplantation, is associated with increased morbidity and mortality following liver transplantation (LT). Hepatitis C virus (HCV) infection is a consistent and modifiable risk factor for PTDM. Prior studies have demonstrated improvement in glucose metabolism following sustained virological response (SVR). However, the effect of SVR on the incidence of PTDM has not been previously investigated in a large cohort of LT recipients. We performed a single-center retrospective cohort study of LT recipients with HCV from January 1, 2010 to June 30, 2015 to compare the risk of sustained posttransplant diabetes mellitus (s-PTDM) prior to and following SVR. SVR was treated as a discrete time varying exposure. The s-PTDM was defined as de novo diabetes mellitus following LT of a >6-month duration. Univariate and multivariate Cox proportional hazards models were used to compare crude and adjusted time to s-PTDM prior to and following SVR. There were 256 eligible LT recipients analyzed. Median follow-up was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior to LT and following LT, respectively. During follow-up, 71 (27.7%) patients developed s-PTDM. The incidence of s-PTDM was greatest in the first year after LT. After adjustment for potential confounders, SVR was associated with a significantly reduced risk of s-PTDM (HR, 0.40; P = 0.048). In conclusion, eradication of HCV is independently associated with a reduced incidence of s-PTDM. This benefit appears to be most influenced by pre-LT SVR and persists throughout the post-LT period. Given the association between PTDM and posttransplant morbidity and mortality, these data provide another motivator for pre-LT or early post-LT treatment of HCV.

Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey.

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.

Living-Donor Liver Transplantation in Hepatitis C Virus Era: A Report of 500 Consecutive Cases in a Single Center.

BACKGROUND: Living donor liver transplantation (LDLT) is considered a safe alternative to deceased donor liver transplantation (DDLT). In Egypt, DDLT program is still awaited, making LDLT the only hope for patients with end-stage liver disease, mainly due to chronic hepatitis C virus (HCV) infection. The current study is conducted to evaluate our experience of LDLT and discuss the lessons learned from 500 consecutive cases in HCV area. METHODS: We reviewed the data of patients who underwent LDLT at Gastrointestinal Surgery Center, Mansoura University during the period between May 2004 and March 2017. RESULTS: During the study period, 500 cases underwent LDLT at our unit. The median age was 51 years, and most of our cases were males (446, 89.2%) and had HCV infection (453, 90.6%). The median MELD score was 15. Median ICU stay was 5 days, and hospital stay was 22 days. Postoperative morbidities occurred in 220 cases (44%). Early mortality occurred in 69 patients (13.8%), and late mortality occurred in 45 patients (9%). The 1-, 3-, 5-, and 7-year overall survival rates of all cases were 80.9%, 78.2%, 75.7%, and 75%, respectively. Preoperative creatinine, worm ischemia, blood transfusion, ICU stay, postoperative morbidities, and small for size syndrome were independent predictors for overall survival. CONCLUSIONS: In countries lacking DDLT, LDLT is the only effective alternative. LDLT requires a teamwork to achieve successful outcomes. LDLT should only be performed in centers with the adequate experience to avoid and decrease the hazards related to this procedure.

Successful combination of direct antiviral agents in liver-transplanted patients with recurrent hepatitis C virus.

AIM: To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection. METHODS: Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications. RESULTS: The majority of patients were IFN-experienced (29/39, 74.4%) and had a history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period. CONCLUSION: Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.

Atypical crusted scabies in a patient with chronic liver disease caused by hepatitis B and D viruses

Abstract: Crusted scabies is a less common variant of scabies that is highly contagious, difficult to treat and involves infestation by Sarcoptes scabiei var. hominis. The classical clinical presentation includes crusted, scaly and generally non-pruritic lesions usually located on the head, neck, palmar, plantar and periungual region. It was first described in Norway in 1848 in patients with leprosy who presented with crusted lesions. In this study, we report the case of a patient with crusted scabies with florid clinical manifestations and chronic liver disease due to hepatitis B and delta virus infection.

How to improve long-term outcome after liver transplantation?

The outcome of liver transplantation has markedly improved in the last 3 decades. Although early post-transplantation outcomes have improved over time, this is not true of the long-term outcome. The majority of late deaths are not related to graft dysfunction, and with the advent of new antiviral agents, recurrence of hepatitis B and hepatitis C after transplantation may no longer represent a source of graft loss and patient's death in the long term. The complications of metabolic syndrome may represent an increasing source of morbidity and mortality after transplantation. This study discusses these modifiable factors associated with late mortality to improve the long-term results of transplantation.