Robotic living donor hepatectomy is associated with superior outcomes for both the donor and the recipient compared with laparoscopic or open - A single-center prospective registry study of 3448 cases.

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

Comparison of the safety and immunogenicity of the BNT-162b2 vaccine and the ChAdOx1 vaccine for solid organ transplant recipients: a prospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.

Living donor liver transplantation in septuagenarians: Better late than never.

BACKGROUND: The coupling of increased life expectancy and improvements in both quality and access to chronic liver disease care, is culminating in an expanding population of septuagenarians (≥70 years) in need of liver transplantation (LT). The objective of this study is to partially alleviate this knowledge deficit and to add clarity to the current status and role of LDLT in this recipient population. METHODS: Of 295 adult patients underwent LDLT between January 1, 2011 and December 31, 2016. Twelve (4%) of these patients were septuagenarians and this group was compared to younger cohort (n = 283). RESULTS: Comorbidity profiles between the two groups were similar and no statistically significant differences were noted in warm/cold ischemia times, operative duration, or blood product utilization. ICU and total hospital stays were comparable. Septuagenarian 1-and 5-year graft and patient survivals were identical at 91.7%. Their younger counterparts had 1-and 5-year patient survivals of 91.1% and 84.0 % accompanied by 1-and 5-year graft survivals of 89.8% and 82.7%, respectively. CONCLUSION: Our study highlights a recognition that LDLT can afford highly-selected elderly patients to access to transplant with equivalent outcomes to those realized by younger recipients.

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.

Efficacy and Safety of Simeprevir or Daclatasvir in Combination With Sofosbuvir for the Treatment of Hepatitis C Genotype 4 Infection.

INTRODUCTION: The combination of sofosbuvir (SOF) with simeprevir (SMV) or daclatasvir (DCV) is very effective in treating hepatitis C virus (HCV) infection, particularly genotype (GT) 1. However, the data on GT4 are very limited. We aimed to determine the efficacy and safety of SOF in combination with either SMV or DCV in GT4-infected patients. PATIENTS AND METHODS: In this real life, prospective, observational study, HCV (GT4) patients (n=96) were evaluated in 2 groups on the basis of the 12-week treatment regimen they received. Group 1 (n=56) patients were treated with SOF and SMV±ribavirin (RBV), whereas group 2 patients were treated with SOF and DCV±RBV (n=40). The primary efficacy endpoint was sustained virologic response 12, whereas the primary safety endpoint was drug discontinuation or occurrence of grade 3/4 adverse events. RESULTS: The mean age was 49±14.6 years (59.4% men). Cirrhosis was present in 53.6% and 35.0% of groups 1 and 2, respectively, whereas 27 patients (48.2%) in group 1 and 21 patients (52.5%) in group 2 had failed prior interferon-based treatment. The median pretreatment HCV-RNA log10 was 6.1 (3.6 to 7.0) and 6.0 (3.6 to 7.2) IU/mL in groups 1 and 2, respectively. RBV was given to 17 patients (30.4%) in group 1 and 2 patients (5%) in group 2. All patients achieved sustained virologic response 12 (100%). Adverse events occurred in 32% of patients (grade 1 and 2), but none discontinued treatment. One patient died in the SMV group (not related to treatment). CONCLUSIONS: SMV/SOF or DCV/SOF combinations are safe and highly effective in HCV-GT4 treatment. Cirrhosis and failure of prior interferon-based treatment did not influence treatment response.

Diminished accuracy of biomarkers of fibrosis in low replicative chronic hepatitis B.

BACKGROUND: We evaluated the diagnostic accuracy of aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), AST/alanine aminotransferase (ALT) ratio (AAR), and age-platelet index (API) for significant fibrosis (Metavir F2-4) in low-replicative (HBV DNA <20,000 IU/mL) chronic hepatitis B virus (HBV) patients. METHODS: The sensitivity, specificity, and area under the receiver-operating characteristic curve (AUROC) of HBeAg-negative, low-replicative (n = 213) and high-replicative (HBV DNA ≥20,000 IU/mL, n = 153) patients was assessed. RESULTS: Overall, 113 patients (30.9%) had F2-4 fibrosis. Of the low and high-replicative patients, 40 (18.8%) and 73 (47.7%) had F2-4, respectively (P < 0.0001). APRI ≥0.5 less frequently identified F2-4 fibrosis in low vs. high-replicative patients (48.7% vs. 69.6%, P = 0.032) and AAR identified it more frequently in low-replicative patients (37.5% vs. 19.4%, P = 0.037). FIB-4 and API were not different (P > 0.05) for identifying F2-4 fibrosis in low and high-replicative patients. Higher specificities were seen at the lowest cut-offs in low vs. high-replicative states for APRI (≥0.5, 98% vs. 68.9%), AAR (84.3% vs. 76.6%), FIB-4 (≥1.45, 97.5% vs. 87.8%) and API (>4, 94.8% vs. 93.8%). At ROC-defined thresholds, APRI (≥0.33), AAR (≥0.93), FIB-4 (≥0.70) and API (>2) showed greater AUROCs for F2-4 diagnosis in low replicative (0.80, 0.62, 0.81 and 0.71, respectively) vs. high-replicative patients (0.73, 0.52, 0.67 and 0.69, respectively). CONCLUSION: All 4 biomarkers in both, low and high-replicative HBV demonstrate modest accuracy for fibrosis diagnosis at conventional cut-offs. Lowering the cut-offs may increase the diagnostic relevance of these biomarkers, particularly for APRI and FIB-4 in low-replicative disease.

Predictors of significant fibrosis in chronic hepatitis B patients with low viremia.

BACKGROUND AND AIM: The data on the prevalence and predictors of significant fibrosis (≥F2, METAVIR) in chronic hepatitis B virus (HBV) patients with low viremia are limited. We aimed to assess both the prevalence predictors of ≥F2 fibrosis in hepatitis B envelope antigen-negative patients with HBV DNA <20,000 IU/mL. METHODS: Hepatitis B envelope antigen-negative patients (n=213) with mean HBV DNA <2000 IU/mL (n=97) and HBV DNA 2000 to 20,000 IU/mL (n=116) were included and all had liver biopsy. Variables significantly associated with ≥F2 fibrosis on an univariate analysis were included in a multivariate logistic regression model. RESULTS: Overall, 40 (18.8%) patients had ≥F2 fibrosis, with no difference between those with mean HBV DNA <2000 IU/mL (19.6%) compared with patients with HBV DNA of 2000 to 20,000 IU/mL (18.1%; P=0.782). Fibrosis ≥F2 was similar in patients with HBV DNA <2000 versus 2000 to 20,000 IU/mL in relation to varying alanine aminotransferase thresholds (P>0.05), and was less frequent in persistently normal alanine aminotransferase patients (13.6%) when compared with those with elevated or fluctuating levels (25.3%, P=0.030). Fewer patients under 40 years of age had ≥F2 fibrosis (12.5%) as compared with older ones (28.2%; P=0.004). Logistic regression analysis identified higher aspartate aminotransferase [odds ratio (OR), 6.21; 95% confidence interval (CI), 2.48-15.54; P<0.0001], lower albumin (OR, 0.86; 95% CI, 0.78-0.95; P=0.002), platelet count (OR, 0.99; 95% CI, 0.98-0.99; P=0.013), and age (OR, 1.05; 95% CI, 1.01-1.09; P=0.024) as independent predictors of significant fibrosis. CONCLUSIONS: A small but significant minority of HBV patients with low viremia harbor significant fibrosis, although its rate is not different in those with viremia above or below 2000 IU/mL. Our findings may guide in decisions regarding liver biopsy and treatment in this category of patients.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFNα-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients. METHODS: Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1 (62.5%) and 4 (37.5%), and significant fibrosis (Metavir ≥ F2) were recruited in an open-label trial with PegIFNα-2a 135-180 µg/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n=31). RESULTS: None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p=0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 ± 32.0 vs. 113.4 ± 62.8, respectively; p=0.140), while levels increased significantly in the controls (106.6 ± 35.6 vs. 142.5 ± 93.0, respectively; p=0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p=1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p=0.008) as an independent predictor of SVR. CONCLUSIONS: PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV.

Accuracy of international guidelines for identifying significant fibrosis in hepatitis B e antigen--negative patients with chronic hepatitis.

BACKGROUND & AIMS: Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis. METHODS: We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173). RESULTS: Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013). CONCLUSIONS: In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.

Recent Advances in Locoregional Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is responsible for 90% of primary hepatic cancer cases, and its incidence with associated morbidity and mortality is growing worldwide. In recent decades, there has been a revolution in HCC treatment. There are three main types of locoregional therapy: radiofrequency ablation, transarterial chemoembolisation, and transarterial radioembolisation. This article summarises recent advances in locoregional methods.

The Diagnostic Performance of Various Clinical Specimens for the Detection of COVID-19: A Meta-Analysis of RT-PCR Studies.

BACKGROUND: The diagnostic performance of numerous clinical specimens to diagnose COVID-19 through RT-PCR techniques is very important, and the test result outcome is still unclear. This review aimed to analyze the diagnostic performance of clinical samples for COVID-19 detection by RT-PCR through a systematic literature review process. METHODOLOGY: A compressive literature search was performed in PubMed/Medline, Scopus, Embase, and Cochrane Library from inception to November 2022. A snowball search on Google, Google Scholar, Research Gate, and MedRxiv, as well as bibliographic research, was performed to identify any other relevant articles. Observational studies that assessed the clinical usefulness of the RT-PCR technique in different human samples for the detection or screening of COVID-19 among patients or patient samples were considered for this review. The primary outcomes considered were sensitivity and specificity, while parameters such as positive predictive value (PPV), negative predictive value (NPV), and kappa coefficient were considered secondary outcomes. RESULTS: A total of 85 studies out of 10,213 non-duplicate records were included for the systematic review, of which 69 articles were considered for the meta-analysis. The meta-analysis indicated better pooled sensitivity with the nasopharyngeal swab (NPS) than saliva (91.06% vs. 76.70%) and was comparable with the combined NPS/oropharyngeal swab (OPS; 92%). Nevertheless, specificity was observed to be better with saliva (98.27%) than the combined NPS/OPS (98.08%) and NPS (95.57%). The other parameters were comparable among different samples. The respiratory samples and throat samples showed a promising result relative to other specimens. The sensitivity and specificity of samples such as nasopharyngeal swabs, saliva, combined nasopharyngeal/oropharyngeal, respiratory, sputum, broncho aspirate, throat swab, gargle, serum, and the mixed sample were found to be 91.06%, 76.70%, 92.00%, 99.44%, 86%, 96%, 94.4%, 95.3%, 73.63%, and above 98; and 95.57%, 98.27%, 98.08%, 100%, 37%, 100%, 100%, 97.6%, and above 97, respectively. CONCLUSIONS: NPS was observed to have relatively better sensitivity, but not specificity when compared with other clinical specimens. Head-to-head comparisons between the different samples and the time of sample collection are warranted to strengthen this evidence.

Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation.

BACKGROUND: Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation (LT). Hence, more patients with diabetes mellitus (DM) are undergoing LT, especially, above the age of 65. AIM: To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65. METHODS: We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record. We assessed the impact of DM on short-term outcomes, one-year, post-LT based on the following variables: Survival at one year; acute cellular rejection (ACR) rates; intensive care unit (ICU) and hospital length of stay; and readmissions. RESULTS: Total of 148 patients who are 65 year or older underwent LT during the study period. The mean age is 68.5 ± 3.3 years and 67.6% were male. The median Model for End-stage Liver Disease score at time of transplantation was 22 (6-39), 39% of patients had hepatocellular carcinoma and 77.7% underwent living donor LT. The one-year survival was similar between DM patients and others, 91%. ACR occurred in 13.5% of patients (P = 0.902). The median ICU stay is 4.5-day P = 0.023. The rates of ICU and 90-d readmission were similar (P = 0.821) and (P = 0.194), respectively. CONCLUSION: The short-term outcome of elderly diabetic patients undergoing LT is similar to others. The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

Hepatocellular Carcinoma Recurrence and Mortality Rate Post Liver Transplantation: Meta-Analysis and Systematic Review of Real-World Evidence.

BACKGROUND: liver transplantation (LT) is the best curative option for eligible patients with hepatocellular carcinoma (HCC), however recurrence remains a major concern. This meta-analysis aimed to investigate the prevalence and risk factors of HCC recurrence. METHODS: studies were selected using PubMed, Epistemonikas, and Google Scholar databases published from inception to 15 May 2022 and a meta-analysis of the proportions was conducted. Observational studies reporting the prevalence of recurrent HCC after an LT were included, with the analysis being stratified by an adherence to the Milan criteria (MC), geographical region, AFP levels, and donor type. RESULTS: out of 4081 articles, 125 were included in the study. The prevalence of recurrent HCC was 17% (CI: 15-19). Patients beyond the MC were more likely to recur than patients within the MC. Asian populations had the greatest prevalence of HCC recurrence (21%; CI: 18-24), whereas North American populations had the lowest recurrence (10%; CI: 7-12). The mortality rate after HCC recurrence was 9%; CI: 8-11. North American populations had the greatest prevalence of mortality with 11% (CI: 5-17). CONCLUSIONS: the recurrence, overall survival, and mortality rates among patients with HCC post-LT remains high, with substantial differences between regions.

First Experience in Living Liver Donation From Donors With Sickle Cell Trait.

Living donor liver transplantation is the main source of organs in the Middle East. Therefore, well balanced criteria are needed to avoid unnecessary exclusion of potential donors, while prioritizing donor safety. We face a high incidence of sickle cell trait (SCT; and disease). Therefore, there is vast experience in general and cardiac surgeries in SCT carriers at our center. After studying their management in detail, we considered accepting SCT carriers as living liver donors, on an exceptional basis. This the first single-center case series of living donor liver transplantation with SCT. Methods: Between January 2012 and September 2021, 20 donors with SCT were reviewed for age, gender, relation to the recipient, hemoglobin, hemoglobin S (HbS), surgical approach, intensive care unit stay, donor and recipients' complications, and graft and recipient survival. Results: Average age of donors was 28.4 y. Sixteen donated the left lateral segment, 4 the left lobe. Recipients were related children or adults. HbS ranged from 21.2% to 39.9%, being ≥30% in 14 donors. HbS was reduced by phlebotomy or exchange transfusion. We performed 7 open, one laparoscopic, and 12 robotic donor surgeries. Operating room time, blood loss, and intensive care unit stay were comparable to non-SCT donors. There was no SCT-related complication. All donors are alive and free of thromboembolic events. Graft and recipient survival is 100% until follow-up. Conclusion: Our experience should encourage other countries with high incidence of SCT to report their experience with this donor population.

Updated thresholds for alanine aminotransferase do not exclude significant histological disease in chronic hepatitis C.

BACKGROUND AND AIM: Histological changes in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT) have not been evaluated for updated upper limits of normal (ULN; ≤ 19/30 U/L for females/males). We assessed significant fibrosis (≥ F2, METAVIR) in patients with PNALT and persistently elevated alanine aminotransferase (PEALT). PATIENTS AND METHODS: Nine hundred and twenty consecutive, unselected HCV patients were stratified into four groups: Group I: (n = 124) PNALT within the updated ULN [0.5 × ULN (corresponding to ≤ 19 U/L) for females; 0.75 × ULN (corresponding to ≤ 30 U/L) for males]; Group II (n = 173): PNALT ≤ 1 × ULN but greater than Group I; Group III (n = 313): PEALT 1-2 × ULN; and Group IV (n = 310): PEALT > 2 × ULN. PNALT was defined as ≥ 3 determinations within the normal range over ≥ 6 months. RESULTS: Advanced ≥ F3 and ≥ F2 fibrosis increased incrementally across Groups I; II; III; and IV: 24.2 and 45.2%; 25.4 and 56.1%; 36.1 and 64.2%; and 50 and 77.1% respectively (P<0.0001 for both). Multivariable logistic regression analysis identified age [odds ratio (OR), 1.05; 95% confidence intervals (CI): 1.02-1.08; P<0.0001], alanine aminotransferase (ALT) groups (OR 1.38; 95% CI: 1.03-1.83; P = 0.030), presence of moderate-severe steatosis (OR 2.70; 95% CI: 1.19-6.15; P = 0.018) and ≥ A2 necroinflammation (OR 17.9; 95% CI: 8.88-36.20; P < 0.0001) as independent predictors of ≥ F2 fibrosis. Updated ULN for ALT were better at excluding ≥ F2 fibrosis compared with traditional ULN (90.6 vs. 74.2%, P = 0.0041) but less specific (20.8 vs. 44%, P = 0.0007) with similar positive/negative predictive values. CONCLUSIONS: HCV patients with 'updated' normal ALT have the lowest prevalence of significant fibrosis, although utilizing these levels without resorting to biopsy would miss significant fibrosis in almost one-half of such patients.

Effect of COVID-19 on liver abnormalities: a systematic review and meta-analysis.

Emerging evidence suggest association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the development of many liver abnormalities. The overarching aim of this study was therefore to assess the available evidence on the clinical effects of SARS-CoV-2 on the profiles of liver chemistries and coagulation in COVID-19 diagnosed patients. We considered all study designs including epidemiological and observational that reported liver function test abnormalities in patients confirmed with SARS-CoV-2 infection. Medline, Embase databases and Google Scholar as well as relevant reviews were searched to identify appropriate studies from inception to 31st of August 2020. We calculated the pooled mean with 95% confidence intervals (95% CI) through a random-effect model meta-analysis. A total of 35 studies with 10,692 participants were considered for the review from which 23 studies with sufficient quantitative data were included in the meta-analysis. The pooled mean for liver enzymes and coagulation parameters did not significantly change in patients diagnosed with COVID-19 and remained within normal range. Notwithstanding potential bias from confounding factors in interpretation of data in this review, findings from the observational studies and case reports suggest that COVID-19 does not appear to have a significant impact on the transaminases or total bilirubin levels of patients with confirmed SARS-CoV-2 infection. Further controlled studies and larger sample size observational studies are needed with adequate reporting of other liver function parameters are warranted.

Long-Term Outcomes of Everolimus Therapy in De Novo Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose. BACKGROUND: To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation. METHODS: We searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently. RESULTS: Eight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR. CONCLUSIONS: The analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.

Conventional Transarterial Chemoembolization Versus Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) occurs in nearly three-quarters of all primary liver cancers, with the majority not amenable to curative therapies. We therefore aimed to re-evaluate the safety, efficacy, and survival benefits of treating patients with drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) compared to the conventional transcatheter arterial chemoembolization (C-TACE). Several databases were searched with a strict eligibility criterion for studies reporting on adult patients with unresectable or recurrent HCC. The pooled analysis included 34 studies involving 4841 HCC patients with a median follow-up of 1.5 to 18 months. There were no significant differences between DEB-TACE and C-TACE with regard to complete response, partial response and disease stability. However, disease control (OR: 1.42 (95% CI (1.03,1.96) and objective response (OR: 1.33 (95% CI (0.99, 1.79) were significantly more effective for DEB-TACE treatment with fewer severe complications and all-cause mortality. The pooled-analysis did not find superiority of DEB-TACE in complete or partial response, disease stability, controlling disease progression, and 30 day or end-mortality. However, results showed that DEB-TACE is associated with a better objective response, disease control, and lower all-cause mortality with severe complications compared to C-TACE treatment. Given that the safety outcomes are based on limited studies with a potential for bias, there was no clear improvement of DEB-TACE over C-TACE treatment.

Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation.

BACKGROUND: Once daily tacrolimus regimen was found to exhibits similar bioavailability, safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients. AIM: To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients. METHODS: MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95% confidence interval (CI) for dichotomous data. RESULTS: Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups (risk ratio: 1.06, 95%CI: 0.84-1.34, n = 758, I2 = 0%) and also we found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I2 = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups. CONCLUSION: The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.