Pungpapong, Surakit

Background/objectives The relationship between nonalcoholic fatty liver disease (NAFLD) and albuminuria has been shown in many epidemiologic studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data and to estimate the risk of albuminuria among patients with NAFLD. Methods Comprehensive literature review was conducted utilizing Medline and Embase database through January 2018 to identify studies that compared the risk of albuminuria among patients with NAFLD versus those without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Nineteen studies (17 cross-sectional studies and two cohort studies) with 24 804 participants fulfilled the eligibility criteria and were included in this meta-analysis. The risk of albuminuria among patients with NAFLD was significantly higher than those without NAFLD with the pooled odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.32–2.11]. Subgroup analysis demonstrated the significantly increased risk of albuminuria among patients with NAFLD without diabetes with pooled OR of 2.25 (95% CI: 1.65–3.06). However, we found no significant association between albuminuria and NAFLD among diabetic patients [pooled OR 1.28 (95% CI: 0.94–1.75)]. Conclusion A significantly increased risk of albuminuria among patients with NAFLD was observed in this meta-analysis. Physicians should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria especially in patients with NAFLD.

Background/ObjectivesStudies have suggested that smokers may have a lower risk of primary sclerosing cholangitis (PSC) although the results have been inconsistent. This systematic review and meta‐analysis was conducted to summarize all available data to better characterize this association.MethodsA comprehensive literature review was conducted using Medline and Embase databases through January 2018 to identify all studies that compared the risk of PSC among current/former smokers versus nonsmokers. Effect estimates from each study were extracted and combined using the random‐effect, generic inverse variance method of DerSimonian and Laird.ResultsSeven case‐control studies with 2,307,393 participants met the eligibility criteria and were included in the meta‐analysis. The risk of PSC among current smokers and former smokers was significantly lower than nonsmokers with the pooled odds ratio of 0.31 (95% CI, 0.18–0.53) and 0.52 (95% CI, 0.44–0.61), respectively. The risk remained significantly lower among current smokers and former smokers compared with nonsmokers even when only patients with PSC without inflammatory bowel disease were included.ConclusionsA significantly decreased risk of PSC among current and former smokers was demonstrated in this study.

The tragedy of the national opioid epidemic has resulted in a significant increase in the number of opioid‐related deaths and accordingly an increase in the number of potential donors designated Public Health Service (PHS) increased risk. Previous studies have demonstrated reluctance to use these PHS organs, and as a result, higher discard rates for these organs have been observed. All patients listed for liver transplantation in the United States from January 2005 to December 2016 were investigated. Patients on the waiting list were divided into 2 groups: those in which a PHS liver was used for transplantation (accepted PHS group) and those in which a PHS liver was declined and transplanted into a recipient lower on the match run (declined PHS group). Intention‐to‐treat patient survival from the time of PHS offer was significantly higher in the accepted PHS compared with the declined PHS group (P < 0.001). On Cox multivariate regression, declining a PHS donor liver was associated with a hazard ratio of 2.36 (95% confidence interval, 2.23‐2.49; P < 0.001). For patients in which a PHS organ offer was declined, 11.6% died or were delisted for being too sick within the subsequent year. Donor liver allografts implanted in the accepted PHS group were of a lower donor risk index (1.28 versus 1.44) compared with the non‐PHS organs that patients in the declined PHS group ultimately received if they underwent transplantation. In conclusion, there is a significantly higher survival for patients in which a PHS liver is accepted and used compared with those patients in which a PHS organ is declined. These data will help inform decisions about whether or not to accept a PHS donor liver for both patients and transplant professionals. Liver Transplantation 24 497–504 2018 AASLD.

AbstractGraft‐versus‐host disease (GVHD) is a rare, fatal complication following orthotopic liver transplantation (OLT). To date, several risk factors have been proposed, but reports on these factors have been inconclusive. This is a retrospective, case–control study of prospectively collected data from 2775OLTs performed at our institution. Eight cases ofGVHDafterOLTwere diagnosed on the basis of the patient's clinical characteristics, and the findings were confirmed with skin and colonic biopsies. Each case was matched to three controls based on the diagnosis of liver disease, recipient's age, and blood group. Univariate and multivariate analyses were performed to identify risk factors associated with the development ofGVHDafterOLT. The univariate and multivariate analyses identified two main risk factors associated with development ofGVHDinOLTrecipients, a difference between recipient and donor age of >20 yr, and any human leukocyte antigen classImatches. Taking these two risk factors into consideration while matching prospective donors and recipients may reduce further incidence ofGVHDinOLTpatients. However, further studies are recommended to validate these findings.

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 ( P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (H epatology 2015;62:1004‐1012)

Treatment with an all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non–liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3‐F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV‐based regimens) received treatment and were followed for a median of 30 weeks (range 12‐53 weeks). The median time from LT to treatment was 32 months (range 2‐317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%‐96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3‐F4 (71%) compared to those with F0‐F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug‐induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. Conclusion : An all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection. (H epatology 2015;61:1880–1886)

AbstractBackground & AimsNon‐ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition.MethodsA retrospective study was performed on patients undergoingLTat our institution from January 2005 to December 2012. Patients who developedNICwere identified. Data collected included demographic and clinical data.ResultsA total 1460 transplants were performed in this period and seventeen patients developedNIC. Pretransplant medianQTc interval was 459 (range, 405–530), and median E/A ratio was 1 (range, 0.71–1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post‐transplant (range, 0–20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50–81) pretransplant to a median of 21% (range, 15–32). Median raw model for end‐stage liver disease (MELD) score was 29 in patients withNICvs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients withNICvs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a medianEFof 44% (range, 25–65%) at the time of discharge. The last echocardiogram available showed a medianEFof 59% (range, 49–73%). One‐year survival of NIC patients was 94.1%.ConclusionNon‐ischaemic cardiomyopathy is a rare complication afterLT. Patients withNICare critically ill, with highMELDscore, and severe malnutrition.

AbstractBackgroundLiver biopsy has been the reference standard when evaluating fibrosis due to recurrent hepatitis after liver transplantation. Magnetic resonance elastography estimates liver stiffness, correlating to fibrosis.AimTo investigate the utility of elastography in staging liver fibrosis in transplant recipients with hepatitis C.MethodsFifty‐four patients, ≥12 months post‐transplant, underwent elastography within three months of biopsy. Discriminatory capability for METAVIR fibrosis stages F0–2 vs. F3–4 and receiver operating characteristic curve (ROC) analysis were determined.ResultsOn biopsy, 27 patients had METAVIR fibrosis score 0–1; 12 had a 3 or 4. There was significant correlation between histologic fibrosis and shear stiffness (R² = 0.588, p < 0.0001). Using a cutoff value of 3.5 kPa, elastography was 91% sensitive and 72% specific in differentiating fibrosis scores of ≥3 from 0 to 1. The AUC of elastography in predicting a fibrosis score of ≥3 was 0.92. Multivariate analysis revealed no correlation between the grade of histologic inflammation and liver stiffness measured by magnetic resonance elastography (R² = 0.265, p = 0.47).ConclusionMagnetic resonance elastography is an accurate non‐invasive technique for excluding stage ≥3 graft in recipients with hepatitis C.

AbstractBackgroundRecent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high‐risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined.MethodsA retrospective cohort study of 227 high‐risk first LTR who received primary anti‐CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post‐transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P‐values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant.ResultsCMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end‐stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance.ConclusionOur results suggest that interventions designed to prevent CMV infection and disease should be applied to all high‐risk LTR until more definitive predictors of these complications are identified.