[CHALLENGES IN LIVER TRANSPLANT 2023].

INTRODUCTION: Liver transplantation improves the survival and the quality of life of patients with liver failure and primary liver carcinoma. Candidates for liver transplantation are thoroughly evaluated to rule out infectious and malignant conditions that might deteriorate following the immune suppression so that their cardiovascular and pulmonary function can sustain them through the surgical procedure. Poor nutritional status, sarcopenia and frailty portend a poor prognosis before and after the transplantation. Steatohepatitis (NASH) emerges as the most common indication for liver transplantation due to liver cirrhosis and liver tumors. NASH patients are often elderly and have comorbidities such as cardiovascular disease, renal failure and sarcopenia. Particular effort should be invested to ameliorate these conditions in order to minimize waiting list dropout and to improve the outcome after surgery. The Israeli Ministry of Health is responsible for the regulation of organ transplants in Israel - by law. It organizes the procurement and allocation of organs and supervises all the transplant activity. All the candidates are listed on the national waiting list and the priority is allocated according to the MELD-Na. Transplant candidates who carry EDI cards (expressing their advanced directive of consent to organ donation after death) receive additional points on the waiting list. Acute liver failure, hepatopulmonary syndrome and hepatocellular carcinoma patients are prioritized according to their condition, as their MELD score does not reflect their prognosis. To overcome the continuous shortage of organs new techniques have been adopted such as living donor liver transplantation, better management of marginal livers, be they from brain dead donors or donations after circulatory death. The main challenges after liver transplantation are the metabolic syndrome and its complications, renal failure and malignancy. An aggressive, early preventive approach is highly recommended to promote a healthy lifestyle, optimize medical therapy and screen for malignancy.

The association between chronic liver diseases and preeclampsia.

BACKGROUND: Preeclampsia is a multisystem disorder characterized by an abnormal vascular response to placentation associated with increased systemic vascular resistance. As liver involvement is one of the main clinical features of preeclampsia, we sought to determine if there is an association between chronic liver diseases and preeclampsia. METHODS: A retrospective matched case-control analysis was conducted in a tertiary medical center. Three hundred eleven (311) pregnant women with preexisting chronic liver disease (study group), including viral and autoimmune hepatitis, non-alcoholic fatty liver, Wilson disease, and cirrhosis, were match for age, parity, and number of fetuses to 933 healthy pregnant women (control group). The primary outcome measure was the incidence of preeclampsia in each group. Secondary outcome measures were obstetrical and neonatal complications. Confounders found to be significant on univariate analysis were evaluated using logistic regression models, and odds ratios (OR) and confidence intervals (CI) were calculated. RESULTS: Preeclampsia was diagnosed in 28 women (9.0%) in the study group and 33 women (3.54%) in the control group (p < 0.001). On multivariate analysis adjusted for maternal age, parity, previous preeclampsia, chronic hypertension, gestational diabetes mellitus, pregestational diabetes mellitus, antiphospholipid syndrome, and mode of conception, chronic liver disease was found to be an independent risk factor for preeclampsia (aOR 2.631, 95% CI 1.518-4.561). Although there was no difference in the gestational week at delivery between the groups (38.6 ± 2.13 vs. 38.8 ± 2.17 for study and control group, respectively, p = 0.410), the study group had a lower mean neonatal birthweight (3088 ± 551 vs. 3182 ± 566 g, p = 0.011). There were no between-group differences in the other parameters evaluated. CONCLUSION: In our study, preexisting chronic liver disease was associated with a 2.6-fold increased risk of preeclampsia.

Using population-level incidence of hepatitis C virus and immigration status for data-driven screening policies: a case study in Israel.

BACKGROUND: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis. METHODS: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined. RESULTS: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively). DISCUSSION: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

Long-term outcomes of Roux-en-Y gastric bypass or sleeve gastrectomy in patients with cirrhosis; before, during or after liver transplantation: A single center's experience.

BACKGROUND: The increasing prevalence of morbid obesity (MO) results in parallel growth of obesity-associated liver diseases necessitating liver transplantation (LT). OBJECTIVE: To examine the feasibility and safety of Roux-en-Y gastric bypass or sleeve gastrectomy in the setting of LT. METHODS: This retrospective chart review included the data on all the MO candidates before and after LT who underwent bariatric surgery (BS) in our institution between 04/2013-09/2016. The reported outcomes were weight change and early and late postoperative complications (mean follow-up: 43 ± 11.1 months). RESULTS: Eighteen MO peri-LT patients (10 females, 8 males, average age 48 years) were included in the study. Ten had cirrhosis (mean Model of End-stage Liver Disease [MELD] score of 12.5 ± 6.42), three underwent concurrent LT and BS (mean MELD score 23.7 ± 0.58), and five had LT (mean of 56 months from LT). The mean percentage of total and excess weight loss was 31% and 81%, respectively. Six of the eight patients with type 2 diabetes mellitus became normoglycemic after BS. Three patients sustained perioperative complications. Two cirrhotic patients died 1 and 4.5 years after BS with decompensation. CONCLUSIONS: Bariatric surgery appears to effectively address obesity in cirrhotic and LT patients. The surgical risk is higher than that of the regular BS population.

Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L-PLUS 2).

Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 109 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 109 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 109 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.

Intrahepatic cholestasis of pregnancy as a risk factor for preeclampsia.

PURPOSE: Intrahepatic cholestasis of pregnancy and preeclampsia are two major pregnancy complications. We aimed to investigate the association between intrahepatic cholestasis of pregnancy (ICP) and preeclampsia. METHODS: Single-center retrospective study. Study group included 180 women (162 singletons and 18 twin gestations) who were diagnosed with ICP based on clinical presentation, elevated liver enzymes and bile acids. The reference group included 1618 women (1507 singletons and 111 twin gestations) who delivered during the study period, and were matched according to age, gravidity, parity and singleton or twin gestation. RESULTS: The incidence of ICP was 0.36%. The incidence of preeclampsia was higher in women with ICP compared to reference group (7.78% vs 2.41%, aOR, 3.74 95% CI 12.0-7.02, p < 0.0001), for either without-(3.89% vs 1.61%, aOR 2.83, 95% CI 1.23-6.5, p = 0.145) or with severe features (3.89% vs 0.80%, aOR 5.17 95% CI 2.14-12.50, p = 0.0003). For both singleton and twin pregnancies, overall preeclampsia rates were higher in the ICP group (5.56% vs 2.19%, aOR 2.91 95% CI 1.39-6.07 p = 0.0045; and 27.78% vs 5.41%, aOR 10.9 95% CI 2.16-47.19, p = 0.0033, respectively). Earlier diagnosis of ICP was associated with higher incidence of preeclampsia (31.1 ± 3.8 vs 34.86 ± 6.2 gestational weeks, p = 0.0259). The average time between ICP diagnosis and to the onset of preeclampsia was 29.7 ± 24 days. CONCLUSION: ICP is associated with an increased risk for preeclampsia. We suggest intensified follow-up for preeclampsia in women with ICP, especially among those with early ICP presentation and twins' gestations.

Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

The Pattern of Elevated Liver Function Tests in Nonalcoholic Fatty Liver Disease Predicts Fibrosis Stage and Metabolic-Associated Comorbidities.

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) and with abnormal liver function tests (LFTs) most commonly present with elevated hepatocellular enzymes (H pattern), but a subset of patients is found to have elevated cholestatic enzymes (C pattern) or a mixed (M) pattern. AIMS AND METHODS: To determine whether the epidemiologic background and comorbidities, as well as the degree of liver fibrosis, differ between NAFLD patients with different patterns of elevated LFTs by retrospectively analyzing data of 106 patients with a biopsy-proven diagnosis of NAFLD. The pattern of elevated LFTs was determined by adopting the "R-Ratio" formula commonly used for drug-induced liver injury. RESULTS: Advanced fibrosis (F > 2) was found in 15 out of 48 (31.3%) patients with a C pattern of elevated LFTs as compared to 2 out of 44 (4.5%) in M patients and 2 out of 11 (18.2%) in H patients (p = 0.004). Group C patients are older and also had a higher prevalence of diabetes, a higher mean hemoglobin A1c, and a higher prevalence of hypertension, as well as a trend for a higher prevalence of hypertriglyceridemia. CONCLUSIONS: Using a simple formula incorporating routine LFTs can help to categorize NAFLD patients as low or high risk for advanced fibrosis stage and metabolic-associated comorbidities.

Characterization of hepatitis B and delta coinfection in Israel.

BACKGROUND: Characteristics of hepatitis B (HBV) and delta (HDV) coinfection in various geographical regions, including Israel, remain unclear. Here we studied HDV seroprevalence in Israel, assessed HDV/HBV viral loads, circulating genotypes and hepatitis delta antigen (HDAg) conservation. METHODS: Serological anti HDV IgG results from 8969 HBsAg positive individuals tested in 2010-2015 were retrospectively analyzed to determine HDV seroprevalence. In a cohort of HBV/HDV coinfected (n=58) and HBV monoinfected (n=27) patients, quantitative real-time PCR (qRT-PCR) and sequencing were performed to determine viral loads, genotypes and hepatitis delta antigen (HDAg) protein sequence. RESULTS: 6.5% (587/8969) of the HBsAg positive patients were positive for anti HDV antibodies. HDV viral load was >2 log copies/ml higher than HBV viral load in most of the coinfected patients with detectable HDV RNA (86%, 50/58). HDV genotype 1 was identified in all patients, most of whom did not express HBV. While 66.6% (4/6) of the HBV/HDV co-expressing patients carried HBV-D2 only 18.5% (5/27) of the HBV monoinfections had HBV-D2 (p=0.03). Higher genetic variability in the HDAg protein sequence was associated with higher HDV viral load. CONCLUSIONS: The overall significant prevalence of HDV (6.5%) mandates HDV RNA testing for all coinfected patients. Patients positive for HDV RNA (characterized by low HBV DNA blood levels) carried HDV genotype 1. Taken together, the significant HDV seroprevalence and the lack of effective anti-HDV therapy, necessitates strict clinical surveillance especially in patients with higher HDV viral loads and increased viral evolution.

Transplantation of Livers from Old Donors: Pushing the Envelope Beyond the Seventh Decade.

BACKGROUND: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C. OBJECTIVES: To examine the efficacy and safety of liver grafts from older donors for transplantation. METHODS: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors. RESULTS: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16-2.63), older donor age (HR = 1.02, 95%CI 1.007-1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06-2.55). CONCLUSIONS: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Risk for hepatitis B and C virus reactivation in patients with psoriasis on biologic therapies: A retrospective cohort study and systematic review of the literature.

BACKGROUND: Patients with psoriasis on biologic therapies and a history of viral hepatitis carry a risk for reactivation. OBJECTIVE: We evaluated safety of biologic therapies in psoriasis patients seropositive for hepatitis B or C viruses (HBV, HCV). METHODS: A retrospective cohort study design was used. Clinical and laboratory data for 30 patients undergoing biologic therapy who were seropositive for HBV or HCV were evaluated. Next, a systematic review was performed. Primary outcomes were hepatitis and viral reactivation during therapy. Treatment duration and antiviral prophylaxis were also recorded. RESULTS: Serology indicated HCV infection in 4 patients, past HBV infection in 17 patients, isolated core antibody in 8 patients, and chronic HBV infection in 1 patient. During follow-up (mean 4.85 ± 3.1 years), no patients experienced hepatitis or viral reactivation. The systematic review of the literature included 49 studies comprising 312 patients followed for a mean of 30.9 months. Viral reactivation occurred in 2/175 patients who were seropositive for core antibody and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively) compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%). Three of these 8 patients with reactivated HBV infection received antiviral prophylaxis. LIMITATIONS: We pooled heterogeneous studies evaluating different biologic therapies. CONCLUSION: Biologic therapies pose minimal risk for viral reactivation in low-risk patients without hepatitis seropositive for HCV or HBV core antibody but are a considerable risk in patients with chronic HBV infection, highlighting the necessity of antiviral prophylaxis.

Safety of Corticosteroid Treatment in Rheumatologic Patients With Markers of Hepatitis B Viral Infection: Pilot Evaluation Study.

BACKGROUND: Immunosuppressive agents may induce hepatitis B flares. The minimal corticosteroid dose and duration of therapy leading to HBV reactivation is unknown. OBJECTIVE: To assess whether short-term corticosteroid therapy for rheumatologic diseases induces HBV reactivation. METHODS: The records of all HBsAg or HBcore antibodies positive, anti-HBs negative patients who were hospitalized in the rheumatology department during 2001-2014 and treated with corticosteroids were reviewed. Alanine aminotransferase (ALT), HBV serology, and serum HBV DNA at baseline and 1-3 months after discharge were recorded. RESULTS: Complete data were found for 23 patients who were hospitalized 73 times for 7 days of treatment with IV corticosteroids. Eighteen patients were HBsAg positive. The mean methylprednisolone dose was 33.9 ± 24 mg/d. The concomitant therapy included DMARDs (15), low-dose corticosteroids (8), and biologicals (10). Serum HBV DNA was detected at baseline in seven patients. Three HBsAg-positive patients treated with cyclophosphamide had HBV hepatitis flare-up with elevated ALT. Two HBsAg-positive patients had reappearance of HBV DNA in serum after treatment with azathioprine and infliximab, respectively, but the ALT levels remained normal. Lamivudine therapy reduced the serum HBV DNA and improved ALT levels in all patients. Corticosteroid therapy by itself did not trigger exacerbation of HBV hepatitis. No HBV reactivation occurred in lamivudine-treated patients after recurrent exposure to biologicals or cyclophosphamide. CONCLUSIONS: Short episodes of corticosteroids seem to be safe in HBV carriers, even in the presence of DMARDs, but lamivudine prophylaxis should be considered for patients exposed to biologicals or cyclophosphamide. Larger prospective trials are needed to establish guidelines.

What tests should you use to assess small intestinal bacterial overgrowth in systemic sclerosis?

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) plays a major role in the pathogenesis of malabsorption in SSc patients and is a source of great morbidity and even mortality, in those patients. This manuscript reviews which tests are valid and should be used in SSc when evaluating SIBO. METHODS: We performed systematic literature searches in PubMed, Embase and the Cochrane library from 1966 up to November 2014 for English language, published articles examining bacterial overgrowth in SSc (e.g. malabsorption tests, breath tests, xylose test, etc). Articles obtained from these searches were reviewed for additional references. The validity of the tests was evaluated according to the OMERACT principles of truth, discrimination and feasibility. RESULTS: From a total of 65 titles, 22 articles were reviewed and 20 were ultimately extracted to examine the validity of tests for GI morphology, bacterial overgrowth and malabsorption in SSc. Only 1 test (hydrogen and methane breath tests) is fully validated. Four tests are partially validated, including jejunal cultures, xylose, lactulose tests, and 72 hours fecal fat test. CONCLUSIONS: Only 1 of a total of 5 GI tests of bacterial overgrowth (see above) is fully validated in SSc. For clinical trials, fully validated tests are preferred, although some investigators use partially validated tests (4 tests). Further validation of GI tests in SSc is needed.

Photoresponsive arylazopyrazole surfactant/PDADMAC mixtures: reversible control of bulk and interfacial properties.

In many applications of polyelectrolyte/surfactant (P/S) mixtures, it is difficult to fine-tune them after mixing the components without changing the sample composition, e.g. pH or the ionic strength. Here we report on a new approach where we use photoswitchable surfactants to enable drastic changes in both the bulk and interfacial properties. Poly(diallyldimethylammonium chloride) (PDADMAC) mixtures with three alkyl-arylazopyrazole butyl sulfonates (CnAAP) with -H, -butyl and -octyl tails are applied and E/Z photoisomerization of the surfactants is used to cause substantially different hydrophobic interactions between the surfactants and PDADMAC. These remotely controlled changes affect significantly the P/S binding and allows for tuning both the bulk and interfacial properties of PDADMAC/CnAAP mixtures through light irradiation. For that, we have fixed the surfactant concentrations at values where they exhibit pronounced surface tension changes upon E/Z photoisomerization with 365 nm UV light (Z) and 520 nm green (E) light and have varied the PDADMAC concentration. The electrophoretic mobility can be largely tuned by photoisomerisation of CnAAP surfactants and P/S aggregates, which can even exhibit a charge reversal from negative to positive values or vice versa. In addition, low colloidal stability at equimolar concentrations of PDADMAC with CnAAP surfactants in the E configuration lead to the formation of large aggregates in the bulk which can be broken up by irradiation with UV light when the surfactant's alkyl chain is short enough (C0AAP). Vibrational sum-frequency generation (SFG) spectroscopy reveals changes at the interface similar to the bulk, where the charging state at air-water interfaces can be modified with light irradiation. Using SFG spectroscopy, we interrogated the O-H stretching modes of interfacial H2O and provide qualitative information on surface charging that is complemented by neutron reflectometry, from which we resolved the surface excesses of PDADMAC and CnAAP at the air-water interface, independently.

Sequential liver and kidney transplantation from a single living donor in two young adults with primary hyperoxaluria type 1.

Using living donor organs for sequential liver and kidney transplantation (SeqLKT) in patients with primary hyperoxaluria type 1 (PH1) has emerged as a viable approach. Taking both organs from a single donor, however, is rare. There are 8 reported cases of SeqLKT in the literature, and in all but 1 case, children were the recipients. We present our experience with SeqLKT in 2 young adults with PH1. In the first case, with an interval between procedures of 4.5 months, SeqLKT was performed with a right liver lobe from a 47-year-old father for his 19-year-old son with PH1 who was on dialysis for 2 years before transplantation. Both the donor and the recipient had an uneventful recovery, although there was re-exploration for the control of bleeding in the recipient after liver transplantation. Thirty-three months after transplantation, the patient had normal liver and renal function. In the second case, with an interval between procedures of 22 days, SeqLKT was performed with organs from a 45-year-old father for his 19-year-old daughter with PH1 who was on dialysis for 8 months. The recipient procedures, including right liver lobe transplantation and kidney transplantation, were uneventful. The donor underwent percutaneous drainage of a subphrenic collection and subsequently fully recovered. Eighteen months after transplantation, the recipient's liver and renal allograft function was normal. In conclusion, because of the severe organ shortage, living related SeqLKT using the same donor should be carefully considered for young adults with PH1.

Effect of Age on Liver Transplantation Recipient Outcomes: Two Centers' Experience.

BACKGROUND: Liver diseases epidemiology has changed with advances in perioperative care. Transplantation at large centers is favorable among older and younger recipients. Local limitations on transplantation for recipients older than 65 years were cancelled in 2014. This study evaluates the effects of age on the transplantation outcome of Israeli patients in the era after removal of the limitations on recipient age. METHODS: This retrospective analysis examined prospective data on patients older than 18 years who underwent liver or liver-kidney transplantation between 2014 and 2019 at 2 transplantation centers. Patients were divided into 4 age groups (group 1: ≤59 years; group 2: 60-64 years; group 3: 65-69 years; and group 4: ≥70 years). Each group's associations of pretransplantation factors with outcome and survival were examined. RESULTS: Two hundred sixty-one recipients underwent 269 transplantations (mean age: 53 ± 12.61 y). There were 181 male (67.8%) and 88 female recipients (67.28%). Overall, 207 patients (79.6%) survived ≥12 months. One-year survival rates were 82.9%, 73.2%, 71.4%, and 93.8% for groups 1 to 4, respectively (not statistically significant; P = .11). One-year graft survival was similar between groups. More patients with chronic obstructive pulmonary disease, diabetes mellitus, or ischemic heart disease tended to survive <12 months. Cardiovascular complication was more common in older groups and affected survival. CONCLUSION: Patient age alone should not be used to deny access to transplantation, which could benefit older nonfrail individuals. However, risk factors such as male sex, chronic obstructive pulmonary disease, ischemic heart disease, diabetes mellitus, and concomitant kidney-liver transplantation should be carefully considered.

Perinatal Outcomes after Liver Transplantation: Is There a Role for Aspirin Treatment?

BACKGROUND: We aimed to describe perinatal outcomes and evaluate aspirin treatment effects in liver-transplanted pregnant women. METHODS: A retrospective study examining perinatal outcomes in liver transplant recipients at a single center (2016-2022). The effect of low-dose aspirin treatment on the risk of developing hypertensive disease in these patients was evaluated. RESULTS: Fourteen deliveries in 11 pregnant liver transplant recipients were identified. Primary liver disease was Wilson's in 50% of pregnancies. The median age was 23 years at transplant and 30 at conception. Tacrolimus was administered in all, steroids in 10 (71.43%), and aspirin (100 mg daily) in 7 (50.0%). Overall, two women (14.28%) developed preeclampsia, and one (7.14%) developed gestational hypertension. Median gestational age at delivery was 37 weeks (31-39 weeks), with six preterm births (between 31-36 weeks) and a median birthweight of 3004 g(range 1450-4100 g). None of those receiving aspirin developed hypertensive disease or suffered excessive bleeding during pregnancy, compared to two (28.57%) with pre-eclampsia in the non-aspirin group. CONCLUSION: Liver-transplanted pregnant women comprise a unique and complex patient population with overall favorable pregnancy outcomes. Based on our single-center experience and due to its safety profile and potential benefit, we recommend low-dose aspirin in all liver transplanted patients during pregnancy for preeclampsia prevention. Further large prospective studies are needed to corroborate our findings.

Urgent Liver Transplantation for Acute Liver Failure in Pregnant Women: The Optimum Timing for Delivery.

BACKGROUND: The occurrence of acute liver failure (ALF) in pregnant women due to an etiology unrelated to pregnancy (pregALF) that leads to liver transplantation (LT) has rarely been reported. The objective was to report the outcome of pregnant women and fetus and propose a strategy for the timing of delivery and of LT in these patients. METHODS: Five consecutive pregnant patients with ALF were admitted to our center between 1986 and 2018 and underwent an LT. A systematic review of case reports concerning patients with pregALF who underwent LT was extracted from the literature. RESULTS: Three with gestational ages (GA) at admission of 15, 22, and 31 weeks of gestation (WG) were transplanted after delivery (n = 1) or intrauterine demise (n = 2) and 2 with GA of 16 and 23 WG before delivery. One infant survived in each group. Among the 32 cases published previously, 11 (34%) had been transplanted after delivery (median GA:31 [28-33]); 10 of these 11 infants were alive at birth. The other 21 mothers were transplanted before delivery (GA:21 WG [18-22]). The median GA at delivery was 30 WG [27.75-37]. Twelve of 21 infants were alive at birth. One-year survival among the ALF patients in our series and in the literature was 100%. Overall, the perinatal survival rate was low (64.8%). CONCLUSIONS: In pregnant patients presenting with ALF not related to the pregnancy, the LT lifesaving procedure had an excellent outcome. Overall, 65% of the infants were alive at delivery with major mortality in those fetus <22 WG despite continued pregnancy.

Serum adipocyte fatty acid binding protein in liver transplant recipients and the metabolic syndrome.

BACKGROUND: Liver transplantation is often associated with metabolic derangements. Adipocyte fatty-acid-binding protein 4 (AFABP4) integrates inflammatory and metabolic responses. It has also been associated with metabolic syndrome in animal models and clinical studies in the general population. AIM: To determine the role of AFABP4 in post-transplant metabolic syndrome. MATERIAL AND METHODS: Consecutive patients followed for at least 6 months after liver transplantation were tested for insulin resistance by homeostasis model assessment (HOMA). Serum levels of AFABP4 were tested by an enzyme-linked immunosorbent assay. RESULTS: The study group included 76 patients (64.5% male, mean age 56.3 ± 12.4 years). Hypertension was present in 56.5%, hyperlipidemia in 69.7%, diabetes mellitus in 23.6%. Half of the patients met at least 3 criteria for metabolic syndrome. Serum AFABP4 levels (p < 0.0001), HOMA index ≥ 2.5 vs. < 2.5 (p < 0.0002) and BMI ≥ 30 vs. < 30 (p < 0.0006) were significantly higher in patients with metabolic syndrome. Within the metabolic syndrome subgroup, AFABP4 levels significantly correlated with age, aspartate aminotransaminase level, waist circumference, and HOMA index. High AFABP4 significantly increased the odds of acquiring metabolic syndrome (OR 1.04, 95% CI 1.007-1.074, p = 0.017). On multiple logistic regression analysis, independent predictors of high AFABP4 were cryptogenic liver disease, steroid administration, high HOMA index, and a high degree of fatty infiltration. CONCLUSION: Prevalence of metabolic syndrome is significantly higher in liver transplant recipients than in the general population. AFABP4 may serve as a circulating biomarker in the clinical prediction/diagnosis of metabolic syndrome in patients post-liver transplantation.

[IGg4 related autoimmune hepatitis].

A 50-year-old man was investigated for painless jaundice. The histologic pattern on the liver biopsy study met the criteria of autoimmune hepatitis. Further clinical and laboratory investigation revealed multi-organ involvement, including Mikulicz's disease of the salivary glands and pancreatic insufficiency. The diagnosis of IgG4-related disease was suggested by a finding of elevated blood levels of IgG4. IgG4-related disease is an inflammatory fibrosing condition characterized by T-cell infiltration of affected organs, presence of IgG4-positive plasma cells, and elevated levels of IgG4 in serum. In the present case, the liver histopathology was compatible with one of several well-defined types of liver involvement in IgG4-related disease. IgG4-related disease may mimic malignant tumors of the biliary tract, pancreas, or liver. Undiagnosed patients may progress to end-stage fibrosis or undergo unnecessary surgery. It is highly important that IgG4-related disease be recognized because it is a treatable condition that responds well to steroids.