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Background and aims Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy. Approach and results Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%. Conclusions TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.

BACKGROUND AND AIMS Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P

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Background & Aims Pre-treatment Tc-99m macroaggregated albumin (MAA) scans are routinely performed prior to transarterial radioembolization (TARE) to estimate lung shunt fraction (LSF) and lung dose. In this study, we investigate LSF observed in early hepatocellular carcinoma (HCC) and provide the scientific rationale for eliminating this step from routine practice. Methods Patients with HCC who underwent Y90 from 2004 to 2018 were reviewed. Inclusion criteria were early stage HCC (UNOS T1/T2/Milan criteria: solitary ≤5 cm, 3 nodules ≤3 cm). LSF was determined using MAA in all patients. Associations between LSF and baseline characteristics were investigated. A “no-MAA” paradigm was then proposed based on a homogenous group that expressed very low LSF. Results Of 1,175 patients with HCC treated with TARE, 448 patients met inclusion criteria. Mean age was 65.6 years and 303 (68%) were males. A total of 352 (79%) had solitary lesions and 406 (91%) unilobar disease. Two-hundred and forty-three (54%), 178 (40%) and 27 (6%) patients were Child-Pugh class A, B and C, respectively. Median LSF was 3.9% (IQR 2.4–6%). Median administered activity was 0.9 GBq (IQR 0.6–1.4), for a median segmental volume of 170 cm3 (range: 60–530). Median lung dose was 1.9 Gy (IQR: 1.0–3.3). The presence of a transjugular intrahepatic portosystemic shunt (TIPS; n = 38) was associated with LSF >10% (odds ratio 12.2; 95% CI 5.2–28.6; p Conclusion LSF is clinically negligible in patients with UNOS T1/T2 HCC without TIPS. When segmental injections are planned, this step can be eliminated, thereby reducing time-to-treatment, number of procedures, and improving convenience for patients traveling from faraway. Lay summary Transarterial radioembolization is a microembolic transarterial treatment for hepatocellular carcinoma. In our study, we found that early stage patients, where segmental injections are planned, exhibited low lung shunting, effectively eliminating the risk of radiation pneumonitis. We propose that the lung shunt study be eliminated in this subgroup, thus leading to fewer procedures, a cost reduction and improved convenience for patients.

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Malnutrition is increasingly being recognized as a poor prognostic factor in the realm of chronic liver disease, particularly among those individuals with end-stage liver disease undergoing transplant evaluation. The purpose of this review is to demonstrate how nutrition contributes to disease pathogenesis and whether improvements in nutrition can alter disease pathogenesis. Recent findings reveal that the role of nutrition is multifaceted, primarily due to alterations in gut microbiota and cytokine release. Additionally, there is increasing data demonstrating that those with gastric bypass are more susceptible to developing end-stage liver disease with lesser amounts of alcohol use. The role of nutrition as relates to liver disease is complex and involves not only global calorie replacement but also management of micronutrient deficiencies. Future research should focus on further tools to assess for malnutrition and prevention of sarcopenia.

Alcohol-associated hepatitis is associated with poor outcomes, especially when severe. Despite extensive study with a plethora of potential therapeutic agents, treatment options remain limited, with the current standard of therapy being corticosteroids. Granulocyte colony-stimulating factor is an alternate agent that seems promising, although further study in a more heterogenous patient population is needed before implementation. Adjuncts to therapy that are often overlooked are alcohol abstinence and adequate optimization of nutrition to improve outcomes. In select patients, early liver transplantation may be an option or enrollment in clinical trials.

Thrombocytopenia commonly occurs in patients with advanced liver disease and can be a contraindication in patients needing combined coronary artery bypass grafting (CABG) and liver transplant (LT). Thrombopoietin receptor agonists, including avatrombopag, are part of a novel drug class and stimulate platelet production. Avatrombopag is indicated in the perioperative setting to avoid platelet transfusions, which carry several disadvantages. Avatrombopag was shown to be safe and effective in patients with chronic liver disease. This study describes the successful use of avatrombopag in a patient with thromboembolic risks in preparation for a combined CABG and LT. Larger clinical trials are necessary to validate our results.

Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician diagnosis of AH at liver transplantation (LT) listing versus UNOS data entry of AH as listing diagnosis. In a prior study, consecutive early LT recipients transplanted for AH between 2012 and 2017 were identified by chart review at 10 ACCELERATE-AH sites. In this current study, these same LT recipients were identified in the UNOS database. The primary UNOS diagnostic code was evaluated for concordance with the chart-review assignment of AH. In cases where the primary listing diagnosis in UNOS was not AH, we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis of AH and alcoholic cirrhosis in the chart; 12 (15%) due to clinical uncertainty regarding the diagnosis of AH versus acute decompensated alcoholic cirrhosis; and 12 (15%) due to a data entry error. In conclusion, in a large cohort of LT recipients with AH, only 35% were documented as such in UNOS. Increased education and awareness for those performing UNOS data entry, the establishment of specific criteria to define AH in the UNOS database, and the ability to document dates of alcohol use would allow future research on ALD to be more informative.

To evaluate hepatocellular carcinoma (HCC) treatment allocation, deviation from BCLC first-treatment recommendation, and outcomes following multidisciplinary, individualized approach. Treatment-naive HCC discussed at multidisciplinary tumor board (MDT) between 2010 and 2013 were included to allow minimum 5 years of follow-up. MDT first-treatment recommendation (resection, transplant, ablation, transarterial radioembolization (Y90), transarterial chemoembolization, sorafenib, palliation) was documented, as were subsequent treatments. Overall survival (OS) analyses were performed on an intention-to-treat (ITT) basis, stratified by BCLC stage. Three hundred and twenty-one patients were treated in the 4-year period. Median age was 62 years, predominantly male (73%), hepatitis C (41%), and Y90 initial treatment (52%). There was a 76% rate of BCLC-discordant first-treatment. Median OS was not reached (57% alive at 10 years), 51.0 months, 25.4 months and 13.4 months for BCLC stages A, B, C and D, respectively. Deviation from BCLC guidelines was very common when individualized, MDT treatment recommendations were made. This approach yielded expected OS in BCLC A, and exceeded general guideline expectations for BCLC B, C and D. These results suggest that while guidelines are helpful, implementing a more personalized approach that incorporates center expertise, patient-specific characteristics, and the known multi-directional treatment allocation process, improves patient outcomes.

Background & Aims Early liver transplantation (LT) for alcoholic hepatitis (AH) is lifesaving but concerns regarding return to harmful alcohol use remain. We sought to identify distinct patterns of alcohol use post-LT to inform pre-LT candidate selection and post-LT addiction care. Methods Detailed post-LT alcohol use data was gathered retrospectively from consecutive patients with severe AH at 11 ACCELERATE-AH sites from 2006–2018. Latent class analysis identified longitudinal patterns of alcohol use post-LT. Logistic and Cox regression evaluated associations between patterns of alcohol use with pre-LT variables and post-LT survival. A microsimulation model estimated the effect of selection criteria on overall outcomes. Results Of 153 LT recipients, 1-, 3-, and 5-year survival were 95%, 88% and 82%. Of 146 LT recipients surviving to home discharge, 4 distinct longitudinal patterns of post-LT alcohol use were identified: Pattern 1 [abstinent](n = 103; 71%), pattern 2 [late/non-heavy](n = 9; 6.2%), pattern 3 [early/non-heavy](n = 22; 15%), pattern 4 [early/heavy](n = 12; 8.2%). One-year survival was similar among the 4 patterns (100%), but patients with early post-LT alcohol use had lower 5-year survival (62% and 53%) compared to abstinent and late/non-heavy patterns (95% and 100%). Early alcohol use patterns were associated with younger age, multiple prior rehabilitation attempts, and overt encephalopathy. In simulation models, the pattern of post-LT alcohol use changed the average life-expectancy after early LT for AH. Conclusions A significant majority of LT recipients for AH maintain longer-term abstinence, but there are distinct patterns of alcohol use associated with higher risk of 3- and 5-year mortality. Pre-LT characteristics are associated with post-LT alcohol use patterns and may inform candidate selection and post-LT addiction care.

Purpose To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile. Materials and Methods This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49–81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4–19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method. Results The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9–11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively. Conclusions Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.

Alcohol-related liver disease generally has been ascribed to men because men reportedly consume alcohol at an increased rate and quantity as compared to women. Recent literature has reported, however, that rates of liver disease attributed to alcohol use by women have increased, largely due, in part, to the increased number of women who consume alcohol regularly. This increase is a paramount concern, as women are more susceptible than men to the effects of alcohol-related liver injury. Health care providers should make efforts to counsel women on the risks of excess alcohol consumption to prevent further increase in alcohol-related liver disease and its associated complications.

Individuals with end-stage liver disease are susceptible to a myriad of highly morbid complications, including hepatorenal syndrome (HRS). This specific type of renal dysfunction in patients with underlying liver disease occurs in pathophysiologically normal kidneys and is a result of renal vasoconstriction secondary to diminished renal blood flow in the setting of worsening hepatic dysfunction. Liver transplantation is curative; shortage of available organs limits access to this beneficial therapy. Medical management of HRS has demonstrated increasing promise. Transjugular intrahepatic portosystemic shunt creation has also been shown to be efficacious in enhancing transplant-free survival, although further study is advisable before widespread implementation of this strategy.

Genotype 3 hepatitis C infection is the second most common genotype worldwide and accounts for most infections in Southeast Asia. It is a particularly ominous genotype because it has been linked to increased mortality, specifically increased late-stage liver events, accelerated development of hepatic fibrosis, and an increased risk of hepatocellular carcinoma. As new treatment regimens for hepatitis C have been emerging, treatment of genotype 3 often requires longer treatment duration with decreased response rates as compared with other genotypes.

A 33-year-old Caucasian female with relapsing-remitting multiple sclerosis presented with abdominal pain, nausea, and vomiting and was found to have acute liver injury. After thorough investigation, she was diagnosed with drug-induced liver injury (DILI) thought secondary to redosing of Natalizumab therapy.

Background Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW). Methods We used multivariable Cox regression to assess whether this "Hispanic paradox" applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database. Results Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease. Conclusions Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.

Background & aimsThe American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients.MethodsWe performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained.ResultsAmong 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P= .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P= .01).ConclusionsIn a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1year (94%) and 3 years (84%), similar to patients receiving livertransplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

Limited data regarding the optimal risk assessment strategy for evaluating candidates for orthotopic liver transplantation (OLT) exist. Our center has adopted a policy of performing cardiac catheterization (CATH) in patients with predefined risk factors, and this is followed by percutaneous coronary intervention (PCI) when it is indicated, even in the presence of negative stress test findings. The aim of this single-center, retrospective study of all patients who underwent OLT between 2000 and 2010 was to assess the effect of our policy on cardiovascular (CV) complications and survival rates after OLT. Data, including 1-year all-cause and CV mortality, postoperative myocardial infarctions (MIs), and frequencies of CATH and PCI, were abstracted. The study was divided into 3 subperiods to reflect the changes in policy over this period: (A) 2000-2004, (B) 2005-2008, and (C) 2009-2010. One thousand two hundred twenty-one patients underwent OLT between 2000 and 2010. The rate of catheterization increased during the 3 time periods (P

Although the MELDNa score is now used for liver transplant allocation in the United States, mortality prediction may be underestimated by the score. Using aggregated electronic health record data from 7,834 adult patients with cirrhosis, we determined whether the cause of cirrhosis/cirrhosis complications is associated with an increased risk of death among patients with a MELDNa ≤15 and whether patients with the greatest risk of death could benefit from liver transplantation (LT). Over a median follow-up of 2.3 years, 3,715 patients had a maximum MELDNa score ≤15. 3.4% were wait-listed for LT. Severe hypoalbuminemia, hepatorenal syndrome and hepatic hydrothorax conferred the greatest risk of death independent of MELDNa score with a 1 year predicted mortality >14%. Approximately 10% possessed these risk factors. Of these high risk patients, only 4% were wait-listed for liver transplantation despite no difference in non-liver comorbidities between patients wait-listed and those not listed. Also, risk factors for death among patients wait-listed were the same as those not wait-listed although the effect of malnutrition was significantly greater for wait-listed patients (HR 8.65 CI 2.57-29.11 versus HR 1.47 CI 1.08-1.98). Using the MELDNa score for allocation may continue to limit access to liver transplantation. This article is protected by copyright. All rights reserved.

Background and Aims The high level of circulating insulin in diabetic patients and the potential proliferative properties of insulin as a result of its cross interaction with insulin-growth factor-I (IGF-I) receptors suggest a proto-oncogenic role on the colonocyte. The aim of our study was to determine whether poor control of diabetes mellitus (DM) is associated with increased prevalence of colonic adenomatous polyps (APs), especially those that are advanced . Methods A retrospective review of all patients with type-2 DM diagnosed with APs from 1996 to 2006 was performed. Hemoglobin A1c (HbA1c) levels were evaluated as an index of glycemic control over the year that preceded the diagnosis of APs. A total of 33 factors were assessed in the patients grouped as well controlled (HbA1c

A 66-year-old man with HIV and recurrent thromboembolism presented with new-onset ascites with an extensive diagnostic work-up that was unremarkable. He was diagnosed with non-cirrhotic portal hypertension after a liver biopsy revealed mild fibrosis and hepatic venography revealed an elevated hepatic venous pressure gradient. The etiology of portal hypertension was attributed to didanosine therapy, a rare but noted side effect.

Data continue to emerge linking the gut-liver axis and nonalcoholic fatty liver disease (NAFLD). More than 500 bacterial species exist within the alimentary tract, the composition of which has been implicated in obesity and its downstream complications. Early animal studies showed that transplantation of gut microbial species from conventionally raised mice into germ-free mice led to increased fat storage and insulin resistance (1). In nonalcoholic steatohepatitis, small intestinal bacterial overgrowth and increased TNF-a production have also been observed. Elevated cytokine concentrations are thought to increase intestinal permeability via disruption of intracellular tight junctions, resulting in progressive inflammation and fibrosis within the liver (2, 3). Interestingly, the host’s interaction with the gut microbiome may be a 2-way street because recent studies have shown that the gut inflammatory response can also influence the components of the microbiota in mice (4). Modulating the gut microbiome via probiotics and prebiotics has been shown to be beneficial in NAFLD in both animal and human studies (5, 6). Probiotics, which are live commensal organisms, and prebiotics, which are nondigestible oligosaccharides and polysaccharides that can stimulate the growth of intestinal bacteria, can be used together in what is known as a synbiotic. A recent meta-analysis reported favorable results with the use of probiotics, specifically declines in concentrations of alanine aminotransferase, aspartate aminotransferase, and TNF-a and measures of insulin resistance (6). Of 4 randomized controlled trials conducted, 2 trials included the use of synbiotics by cotreatment with fructooligosaccharides (FOS), a prebiotic (7, 8). FOS can promote potentially beneficial growth of bifidobacteria, and a trial using FOS alone was reported to cause improvement in aminotransferases (9). Of note is that one of the previous trials in patients with nonalcoholic steatohepatitis included liver biopsies that showed improved liver histology after 6 mo of a synbiotic containing Bifidobacterium longum and FOS (7). In this issue of the Journal, Eslamparast et al (10) add to this evidence with the results of a study that used a synbiotic formulation in NAFLD in a double-blind, randomized, placebocontrolled trial. Fifty-two nondiabetic patients with newly diagnosed NAFLD by ultrasound and an alanine aminotransferase concentration .60 U/L were randomly assigned to receive a synbiotic formulation including Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophiles, Bifidobacterium breve, Lactobacillus acidophilus, B. longum, and Lactobacillus bulgaricus with FOS or placebo and were followed for 28 wk. Important findings of this study were improvements in aminotransferases as well as a decline in baseline mild fibrosis as estimated by FibroScan (echosens). Whereas this study did not include liver histology as an endpoint, the authors provided evidence that systemic inflammation decreased with a decline in circulating TNF-a concentrations and diminished nuclear transcription factor jB activation in circulating mononuclear leukocytes. These observations are consistent with previous findings with both probiotics and prebiotics (6). Whether these measures represent inflammation at the level of the gut, the liver, adipose tissue, or throughout the body remains to be determined. Without specific interventions to manipulate components of the inflammation (eg, anti–TNF-a therapies or other specific pharmacologic antiinflammatory approaches), which components of inflammation play a causal role and which are consequences of liver injury is yet to be sorted out. It is tempting to attribute causality to the inflammatory axis as the authors of this study did, but it may be premature to do so without confirmatory data. The use of FibroScan to measure liver stiffness in this trial yielded provocative data. There appeared to be a reduction in liver stiffness, but it is worth noting that both the preand posttreatment liver stiffness measures were near normal. Liver stiffness measures are also influenced by the degree of steatosis and other factors such as the fasting state of the subject (11). Without corresponding liver biopsies, it is difficult to know the meaning of improved liver stiffness values when the values are near the normal range. Although the number of subjects treated was relatively small, this study supports the safety of synbiotic use and corroborated the findings of previous trials with improvement in not only aminotransferases but also measures of fibrosis, cytokine concentrations, and insulin sensitivity. Future studies with long-term follow-up after stopping treatment to assess if the benefits of

Drug-induced liver injury (DILI) is a rare but potentially devastating adverse drug reaction. Its presentation can range from asymptomatic elevation in liver biochemistries to fulminant liver failure. Over the past decade, clinical and research interest in the field of idiosyncratic DILI has been intense, and several new findings have been reported. In this article, we provide an update on implicated agents, clinical features, outcomes, and the results of recently reported genetic studies.