Hepatitis C virus-positive donors in HCV-negative recipients in liver transplantation: Is it possible in Mexico?

Hepatitis C virus (HCV) infection is a worldwide public health problem associated with significant morbidity and mortality. In the context of liver transplantation, the demand for organs continues to exceed the supply, prompting the consideration of using organs from HCV-positive donors in HCV-negative recipients. The introduction of direct-acting antivirals (DAAs), which have demonstrated great efficacy in eradicating the virus, has made transplantation of organs from donors with HCV infection possible. The present article provides a brief review of the current evidence on the use of organs from HCV-infected patients.

Hepatitis C treatment and long-term outcome of patients with hepatocellular carcinoma after resection.

BACKGROUND AND AIM: This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma. METHODS: This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed. RESULTS: After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events. CONCLUSION: In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.

Hepatitis C donor positive to recipient negative solid organ transplants: Early direct acting antiviral insurance approval rates with and without documented viremia.

BACKGROUND: Current guidelines support early initiation of direct-acting antivirals (DAA) in hepatitis C virus (HCV) donor positive and recipient negative (D+/R-) solid organ transplants (SOTs). According to experts, access to DAA therapy is a key barrier to early treatment. METHODS: This single-center, retrospective study assessed the rate of DAA prescription approval with or without confirmed HCV viremia, time to approval, and reasons for denial in HCV D+/R- SOTs. RESULTS: All 51 patients received insurance approval for DAA therapy following transplantation regardless of confirmed HCV viremia at time of prior authorization (PA) submission. Same day PA approval was obtained in 51% of cases. Appeals received approval within a median of 2 days from submission. CONCLUSION: Our findings suggest confirmed HCV viremia may not be as significant of a barrier to DAA access and may encourage other health systems to consider early initiation of DAA therapy in their HCV D+/R- transplants.

Treating Hepatitis C Prior to Total Hip Arthroplasty is Cost-effective: A Markov Analysis.

BACKGROUND: Patients infected with the hepatitis C virus (HCV) have high complication rates following total hip arthroplasty (THA). Advances in HCV therapy now enable clinicians to eradicate the disease; however, its cost-effectiveness from an orthopaedic perspective remains to be demonstrated. We sought to conduct a cost-effectiveness analysis comparing no therapy to direct-acting antiviral (DAA) therapy prior to THA among HCV-positive patients. METHODS: A Markov model was utilized to evaluate the cost-effectiveness of treating HCV with DAA prior to THA. The model was powered with event probabilities, mortality, cost, and quality-adjusted life year (QALY) values for patients with and without HCV that were obtained from the published literature. This included treatment costs, successes of HCV eradication, incidences of superficial or periprosthetic joint infection (PJI), probabilities of utilizing various PJI treatment modalities, PJI treatment success/failures, and mortality rates. The incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $50,000/QALY. RESULTS: Our Markov model indicates that in comparison to no therapy, DAA prior to THA is cost-effective for HCV-positive patients. THA in the setting of no therapy and DAA added 8.06 and 14.39 QALYs at a mean cost of $28,800 and $115,800. The incremental cost-effectiveness ratio associated with HCV DAA in comparison to no therapy was $13,800/QALY, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Hepatitis C treatment with DAA prior to THA is cost-effective at all current drug list prices. Given these findings, strong consideration should be given to treating patients for HCV prior to elective THA. LEVEL OF EVIDENCE: Cost-effectiveness Analysis; Level III.

Association of Viral Hepatitis Status and Post-hepatectomy Outcomes in the Era of Direct-Acting Antivirals.

BACKGROUND: The role of viral hepatitis status in post-hepatectomy outcomes has yet to be delineated. This large, multicentred contemporary study aimed to evaluate the effect of viral hepatitis status on 30-day post-hepatectomy complications in patients treated for hepatocellular carcinoma (HCC). METHODS: Patients from the National Surgical Quality Improvement Program (NSQIP) database with known viral hepatitis status, who underwent hepatectomy for HCC between 2014 and 2018, were included. Patients were classified as HBV-only, HCV-only, HBV and HCV co-infection (HBV/HCV), or no viral hepatitis (NV). Multivariable models were used to assess outcomes of interest. The primary outcome was any 30-day post-hepatectomy complication. The secondary outcomes were major complications and post-hepatectomy liver failure (PHLF). Subgroup analyses were performed for cirrhotic and noncirrhotic patients. RESULTS: A total of 3234 patients were included. The 30-day complication rate was 207/663 (31.2%) HBV, 356/1077 (33.1%) HCV, 29/81 (35.8%) HBV/HCV, and 534/1413 (37.8%) NV (p = 0.01). On adjusted analysis, viral hepatitis status was not associated with occurrence of any 30-day post-hepatectomy complications (ref: NV, HBV odds ratio (OR) 0.89 [95% confidence interval (CI): 0.71-1.12]; HCV OR 0.91 [95% CI: 0.75-1.10]; HBV/HCV OR 1.17 [95% CI: 0.71-1.93]). Similar results were found in cirrhotic and noncirrhotic subgroups, and for secondary outcomes: occurrence of any major complications and PHLF. CONCLUSIONS: In patients with HCC managed with resection, viral hepatitis status is not associated with 30-day post-hepatectomy complications, major complications, or PHLF compared with NV. This suggests that clinical decisions and prognostication of 30-day outcomes in this population likely should not be made based on viral hepatitis status.

Antiviral Treatment for Hepatitis C Is Associated With a Reduced Risk of Periprosthetic Joint Infection: A Meta-Analysis of Observational Studies.

BACKGROUND: Recently, preoperative antiviral therapies for hepatitis C virus (HCV) have become available for total joint arthroplasty (TJA) patients. The objective of this meta-analysis is to investigate the impact of anti-HCV treatment on the incidence of postoperative complications after primary TJAs. METHODS: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases for relevant studies from inception to March 5, 2022. The pooled odds ratios with 95% CI of the risk of postoperative complications were calculated using the random effects model. Subgroup analyses were conducted on the basis of surgery type, antiviral regimes, and duration of follow-up. RESULTS: Eight retrospective cohort studies fulfilled the inclusion and exclusion criteria, involving 9,703 subjects. Overall, antiviral therapy for HCV was associated with a reduced risk of all-type complications and surgical complications. Moreover, we found that HCV-infected patients without treatment had substantially higher rates of periprosthetic joint infection at any surgery type and follow-up time point. There was a tendency for favoring a lower pooled revision/reoperation rate and mechanical complication rate in treated patients compared with untreated patients, but the differences failed to reach statistical significance. When limiting analysis to patients receiving preoperative direct acting antiviral-based therapy, untreated patients still had a higher surgical complication rate and joint infection rate. CONCLUSION: This meta-analysis demonstrated that antiviral therapy for HCV appears to be associated with a reduced risk of surgical complications in TJA patients, particularly periprosthetic joint infection. Thus, direct-acting antiviral therapy could be recommended for patients diagnosed with HCV.

Eficacia y seguridad de sofosbuvir / velpatasvir en pacientes adultos postrasplante de medula ósea con infección crónica por el virus de la hepatitis C, con grado de fibrosis hepática F0 y sin tratamiento previo / Efficacy and safety of sofosbuvir/velpatasvir in adult post-bone marrow transplant patients with chronic hepatitis C virus infection, with liver fibrosis grade F0 and without prior treatment

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de sofosbuvir/velpatasvir (SOF/VEL) en pacientes adultos postrasplante de medula ósea con infección crónica por el virus de la hepatitis C (VHC), con grado de fibrosis hepática FO y sin tratamiento previo. Así, la Dra. Estefanía Liza Baca especialista en Gastroenterología del Hospital Nacional Edgardo Rebagliati Martins, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso fuera del petitorio del producto SOFNEL. ASPECTOS GENERALES: La infección crónica por el virus de la hepatitis C (VHC) sigue siendo un problema de salud pública, a nivel mundial, con 71 millones de personas viviendo con el VHC. De ellos, aproximadamente, de 290 000 a 399 000 pacientes por año fallecen por complicaciones asociadas, incluyendo cirrosis hepática, carcinoma hepatocelular y falla hepática (OMS 2021; 2017). En el Perú, la prevalencia de infección crónica por el VHC no se conoce con exactitud; sin embargo, de acuerdo a algunos estudios seroepidemiológicos realizados en el país, se ha estimado entre 0.25 % a 1 % aproximadamente, con una tasa de mortalidad por el VHC de 0.04 por 100 000 habitantes (Colichon Yerosh et al. 2004; Dávalos Moscol 2009; Farfán y Cabezas 2003; Sanchez et al. 2000). Algunos pacientes con infección crónica por el VHC presentan comorbilidades u otras condiciones (i.e. trasplante de células madre) que pueden acelerar la progresión de la enfermedad a problemas hepáticos graves como: cirrosis, cáncer hepático y necesidad de trasplante hepático. El objetivo de la terapia antiviral en pacientes con infección crónica por el VHC es disminuir el ARN del VHC a niveles indetectables (AASLD 2021; EASL 2020), definido mediante el logro de una respuesta viral sostenida a las 12 semanas después del tratamiento (RVS12) (Chopra 2020). La ribavirina y el interferón pegilado han sido tradicionalmente los \ tratamientos para la infección crónica por el VHC; sin embargo, en los últimos años, el """" " " I desarrollo de los agentes antivirales de acción directa (AAD) y AAD pangenotípicos han ido 1 desplazando su uso, debido a mejores tasas de RVS (e.g. SOFNEL) con mejores perfiles de seguridade. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad de SOFNEL en pacientes adultos postrasplante de medula ósea con infección crónica por el VHC, con grado de fibrosis hepática FO y sin tratamiento previo. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Scottish Medicines Consortium (SMC), el Scottish Intercollegiate Guidelines Network (SIGN), el Institute for Quality and Efficiency in Healthcare (IQWiG por sus siglas en alemán), la International Database of GRADE Guideline, el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Guidelines International Network (GIN), National Health and Medical Research Council (NHMRC), la Cancer Guidelines Database, el New Zealand Guidelines Group (NZGG), el Instituto de Evaluación Tecnológica en Salud (IETS), el Instituto de Efectividad Clínica y Sanitaria (IECS), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), la OMS, el Ministerio de Salud del Perú (MINSA) y el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en estudios del hígado, infectología y trasplante de medula ósea, tales como: la American Association for the Study of Liver Disease (AASLD), la European Association for the Study of the Liver (EASL), la Infectious Diseases Society of America (IDSA), American Society for Blood and Marrow Transplantation, Finalmente, se realizó una búsqueda en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica hasta diciembre de 2021, se identificó una GPC elaborada por la European Association for the Study of the Liver en el 2020 (EASL 2020). No se identificaron ETS, ECA o RS de ECA o estudios observacionales comparativos que respondieran a la pregunta PICO de interés del presente dictamen. En tal sentido se optó por incluir el ECA que sirvió de base para la aprobación de SOFNEL ante la Food and Drug Administration y la European Medicine Agency. Así, se incluyó al ECA ASTRAL-1 publicado por Feld et al. en el 2015. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de SOFNEL para pacientes adultos postrasplante de medula ósea con infección crónica por el VHC, con grado de fibrosis hepática FO y sin tratamiento previo, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

[Laparoscopic Posterolateral Sectionectomy in Hepatocellular Cacinoma - Increasing Oncological Precision by Combining the Glissonean Pedicle Approach and Fluorescence Guidance]. / 1 Laparoskopische posterolaterale Sektionektomie beim hepatozellulären Karzinom ­ Erhöhung der onkologischen Präzision durch Kombination des Glissonean Pedicle Approach und der Fluoreszenznavigation.

AIM: Minimally invasive procedures have been increasingly performed in liver surgery. Benefits include lower intraoperative blood loss, reduced postoperative morbidity and shorter lengths of hospital stay in comparison to open liver surgery. Exact resection margins seem advantageous in primary liver cancer but challenging to implement with minimally invasive techniques. In this case report, we aimed to increase surgical precision by combining the Glissonean pedicle approach and intraoperative fluorescence guidance. INDICATION: A 73-year-old female patient with CHILD A liver cirrhosis with chronic hepatitis C virus infection was transferred to our hospital with high levels of alpha-fetoprotein (792 ng/ml). Sectional imaging confirmed the suspected diagnosis of a single hepatocellular carcinoma (HCC) with a size of 2.2 cm in segments VI/VII. In line with the local tumour board recommendation, an anatomical posterolateral sectionectomy using the Glissonean pedicle approach was planned. METHODS: The patient was placed in the French position. After mobilisation of the right liver, the posterolateral pedicle was encircled and transected. 0.2 mg/kg of body mass indocyanine green (ICG) was then injected intravenously. The perfused parenchyma of segments I-V and VIII turned green, but the unperfused posterolateral segment VI and VII remained native. The transection line was marked under ICG-imaging to indicate the transition of the posterolateral to the anteromedial sector. Parenchymal transection was performed under intermittent ICG-guided imaging. Pathological workup confirmed R0 resection of a well differentiated HCC in a cirrhotic liver (grade 4). The patient was discharged from the hospital on the 6th postoperative day after an uncomplicated course and was confirmed to be tumour-free six months after surgery. CONCLUSION: As an additional intraoperative tool, ICG-imaging may provide visualisation of segment and sector boundaries and thus may enable precise anatomical resection. Prospective studies are needed to evaluate the added value of this technique, especially with regard to the rate of R0 resections.

The impact of hepatitis C virus direct acting agents in liver transplant using very old donor grafts: a real-world single-center analysis.

The correct timing of use of direct acting agents (DAAs) among transplanted patients remains unknown. The aim of this paperwork is to evaluate the impact of DAAs treatment in pre- or peri-operative period in liver transplantation when grafts ≥ 70 years are used. This is a retrospective analysis comparing adult liver transplant performed for HCV-related cirrhosis and/or hepatocarcinoma using a graft ≥ 70 in the period 2015-2018 (Group DAA-HCV-OLD, study group) to three different groups: (a) anti-HCV-Ab-negative patients receiving graft ≥ 70 (no-HCV-OLD), (b) anti-HCV-Ab-negative patients receiving a graft aged 18-69 years (no-HCV-YOUNG), and (c) anti-HCV-Ab-positive patients receiving a donor graft ≥ 70 in the period 2007-2011 (no-DAA-HCV-OLD). Totally, 528 liver transplants were considered: 164 in DAA-HCV-OLD, 143 in no-HCV-OLD, 120 in no-HCV-YOUNG and 101 in no-DAA-HCV-OLD Group. Graft survival rates at 1 and 3 years were 88% and 81% in DAA-HCV-OLD Group, 82% and 68% in no-DAA-HCV-OLD (p = 0.007), 89% and 84% in no-HCV-OLD (p = 0.76), and 94% and 92% in no-HCV-YOUNG (p = 0.02). No differences were observed among groups in the incidence of primary non-function, primary dysfunction, vascular or biliary complications. DAAs were able to zero HCV-related graft loss, with a 3-year graft survival > 80%. The outcomes of older graft recipients became equal irrespectively of their HCV serological status.

Serum MicroRNA Transcriptomics and Acute Rejection or Recurrent Hepatitis C Virus in Human Liver Allograft Recipients: A Pilot Study.

BACKGROUND: Acute rejection (AR) and recurrent hepatitis C virus (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management. METHODS: We performed small RNA sequencing and microRNA (miRNA) microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized real-time quantitative PCR (RT-qPCR) assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve. RESULTS: Nine miRNAs-miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210, and miR-885-5p-were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P < 0.0001) as the best statistical model and miR-122 + miR-210 (P < 0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis. CONCLUSIONS: Circulating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to R-HCV.

Changing trends in liver transplantation indications in Saudi Arabia: from hepatitis C virus infection to nonalcoholic fatty liver disease.

BACKGROUND: Several trend analyses on liver transplantation (LT) indications have been published in the U.S. and in other countries, but there are limited data on LT indication trends in Saudi Arabia (SA), especially since the availability of direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV). This study aimed to analyze trends in the frequency of LT indications among LT recipients in SA over a 19-year period and examine associations between etiologic-specific trends and clinicodemographic characteristics. METHODS: This retrospective study analyzed clinical and surgical data of adult patients (n = 1009) who underwent LT at the King Faisal Specialist Hospital & Research Center (Riyadh, SA) between 2001 and 2019. Spearman's rank correlation, Poisson regression, and Joinpoint regression analysis were employed to assess changes in LT etiologic trends. RESULTS: In the first period (2001-2010), the main LT indications were HCV (41.9%) and hepatitis B virus (HBV) (21.1%), but nonalcoholic steatohepatitis (NASH) (29.7%) surpassed HCV (23.7%) as the leading LT indication in the second period (2011-2019); and the trends were significant in correlation analyses [incidence rate ratio (IRR) = 1.09 (1.06-1.13) for NASH; IRR = 0.93 (0.91-0.95) for HCV]. In the Joinpoint regression analysis, increases in NASH from 2006 to 2012 (+ 32.1%) were statistically significant, as were the decreases in HCV from 2004 to 2007 (- 19.6%) and from 2010 to 2019 (- 12.1%). Similar patterns were observed in LT etiological comparisons before and after the availability of DAAs and within hepatocellular carcinoma stratifications. CONCLUSIONS: Trends in the epidemiology of LT indications among LT recipients in SA have changed over a 19-year period. Most notably, NASH has eclipsed HCV in the country due to the effective treatment strategies for HCV. These trends in NASH now need an aggressive public health response to minimize and avert future onset of additional clinical and economic strains on health care systems and LT centers in SA.

Retransplantation outcomes for hepatitis C in the United States before and after direct-acting antiviral introduction.

The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post-liver transplant (LT) outcomes. We investigated the trends and outcomes of retransplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Multiorgan transplants and patients with >2 total LTs were excluded. Two eras were defined: pre-DAA (2009-2012) and post-DAA (2014-2017). A total of 2112 re-LT patients were eligible (HCV: n = 499 pre-DAA and n = 322 post-DAA; non-HCV: n = 547 pre-DAA and n = 744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA (P < .001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA (P < .001). Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival (hazard ratio [HR]: 0.67; P = .005, and HR: 0.65; P = .004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence (HR: 0.31; P = .002, HR 0.32; P = .003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.

Quantitative assessment of liver fibrosis by digital image analysis reveals correlation with qualitative clinical fibrosis staging in liver transplant patients.

Technologies for digitizing tissues provide important quantitative data for liver histopathology investigation. We aimed to assess liver fibrosis degree with quantitative morphometric measurements of histopathological sections utilizing digital image analysis (DIA) and to further investigate if a correlation with histopathologic scoring (Scheuer staging) exists. A retrospective study of patients with at least two post-liver transplant biopsies having a Scheuer stage of ≤ 2 at baseline were gathered. Portal tract fibrotic percentage (%) and size (µm2) were measured by DIA, while clinical fibrosis score was measured by the Scheuer system. Correlations between DIA measurements and Scheuer scores were computed by Spearman correlation analysis. Differences between mean levels of fibrosis (score, size, and percentage) at baseline versus second visit were computed by Student's t-test. P values < 0.05 were considered significant. Of 22 patients who met the study criteria, 54 biopsies were included for analysis. Average levels ±standard error [S.E.] of portal tract fibrotic percentage (%) and size (µm2) progressed from 46.5 ± 3.6% at baseline to 61.8 ± 3.8% at the second visit (P = 0.005 by Student's t-test), and from 28,075 ± 3,232 µm2 at base line to 67,146 ± 10,639 µm2 at the second visit (P = 0.002 by Student's t-test), respectively. Average levels of Scheuer fibrosis scores progressed from 0.55±0.19 at baseline to 1.14±0.26 at the second visit (P = 0.02 by Student's t-test). Portal tract fibrotic percentage (%) and portal tract fibrotic size were directly correlated with clinical Scheuer fibrosis stage, with Spearman correlation coefficient and P value computed as r = 0.70, P < 0.0001 and r = 0.41, P = 0.002, respectively. Digital quantitative assessment of portal triad size and fibrosis percentage demonstrates a strong correlation with visually assessed histologic stage of liver fibrosis and complements the standard assessment for allograft monitoring, suggesting the utility of future WSI analysis.

Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD: A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS: Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS: LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.

Ex vivo perfusion in lung transplantation and removal of HCV: the next level.

The large gap between high demand and low availability of lungs is still a limiting factor for lung transplantation which leads to important mortality rates on the waiting list. In the last years, with the advent of potent direct-acting antivirals (DAAs), donors carrying active hepatitis C (HCV) infection became an important source in expanding the donor pool. Recent clinical trials exploring different treatment regimens post-transplantation when using HCV-positive abdominal and thoracic organs into HCV-negative recipients have shown encouraging results. Although early data shows no toxicity and similar survival rates when compared to non-HCV organ transplantation, long-term outcomes evaluating the effect of either the transmission of HCV into the recipients or the deliberate use of DAAs to treat the virus remains absent. An important and innovative strategy to overcome this limitation is the possibility of mitigating viral transmission with the use of ex vivo donor organ treatment prior to transplantation. Recent pre-clinical and clinical studies explore the use of ex vivo perfusion and the removal of HCV prior to transplantation with the addition of other innovative therapies, which will be reviewed in this article.

Hepatitis C and Racial Disparity in Liver Transplant Waitlist Additions : Separate Not Equal.

BACKGROUND: In 2014, direct-acting antivirals (DAAs) became available for hepatitis C virus (HCV) with successful results. Since their implementation, the rate of HCV waitlist (WL) for liver transplantation (LT) has decreased, but significant ethnic disparities exist. We hypothesized that the rate of decline for HCV WL for LT is different across the various racial groups. METHODS: We conducted a retrospective cohort study using Organ Procurement and Transplantation Network data reports of adult LT candidates from 2014 to 2018. RESULTS: Overall, there was a decline in HCV WL rates for all ethnic groups (Caucasians, African Americans [AA], and Hispanics). However, the WL rates were significantly higher in AA compared with Caucasians each year, and this trend was continuous across the 5-year period. There were no differences in WL rates between Caucasians and Hispanics. DISCUSSION: The results show that health care disparities related to HCV disproportionately affect AA. The factors associated with this disparity need to be explored further to develop mechanisms to address these differences. By understanding the HCV treatment disparities across racial groups, modifications to HCV treatment nationwide can be adopted. Additional emphasis should be placed on AA to help reduce their WL rate, as well as redistributing resources to promote health care equity.

Simultaneous Deceased Donor Liver and Kidney Transplantation in a Human Immunodeficiency Virus/Hepatitis C Virus -Coinfected Patient With Hemophilia in Japan: A Case Report.

The authors describe the first case of simultaneous liver and kidney transplantation (SLK) in a human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patient with severe hemophilia in Japan, and it could be second case in the world. The patient was a 61-year-old Japanese man with HCV cirrhosis complicated with HIV coinfection through contaminated blood product for hemophilia B at age 1 year. The patient's liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 38. He had been on hemodialysis for 6 years, but HIV RNA and HCV RNA had been undetectable after appropriate antiviral therapies. In September 2019, the patient underwent successful deceased donor (DD) SLK. The donor was a man in his 60s deceased due to cerebral hemorrhage. Regular DD liver transplantation was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 566 min, and the graft liver weighed 1154 g. The graft kidney was transplanted extraperitoneally in the right iliac fossa. The administration of clotting factor IX was discontinued on day 3. The immunosuppressive regimen was based on intravenous induction with 2 mg/kg of basiliximab and 1 g methylprednisolone and subsequent oral administration of mycophenolate mofetil and prednisolone, followed by low-dose tacrolimus after 1 week for kidney-sparing purpose. Steroid therapy was gradually discontinued at 3 months after SLK. The same pretransplantation antiretroviral therapy (ART; tenofovir and dolutegravir) was introduced after 3 days when the CD4 cell count was more than 300/µL and HIV RNA was within an undetectable range. The postoperative course was uneventful without infectious complication, and the patient was transferred to a referral hospital on day 90 and discharged home on day 111. Strategic surgical planning and meticulous pre- and post-transplant management of ART and clotting factors could lead to the success of SLK.