A natural language processing algorithm accurately classifies steatotic liver disease pathology to estimate the risk of cirrhosis.

BACKGROUND: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. METHODS: From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. RESULTS: The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. CONCLUSIONS: The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.

Controversies in terlipressin and transplantation in the United States: How do we MELD the two?

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss the proposed next steps for studying terlipressin implementation in the United States. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.

Improving the Consent Process With an Informed Consent Video Prior to Outpatient Colonoscopy.

BACKGROUND AND AIMS: Informed consent should allow patients the appropriate time and conditions to make decisions about their care. However, consent is often obtained immediately prior to a colonoscopy. We conducted a quality improvement study to assess how a preprocedure consent video 2 days prior to an outpatient colonoscopy impacts patient satisfaction. METHODS: Patients undergoing outpatient colonoscopy at a large academic medical center opted in to a text messaging platform for procedural information. Our intervention was an informed consent video 2 days before the colonoscopy. Our primary outcome was a composite patient satisfaction score. Pre and postintervention scores were compared using ordinal or multinomial logistic models to calculate odds ratios (OR) or relative risk ratios and 95% confidence intervals (CI), adjusting for age and sex. RESULTS: 1109 and 1452 patients completed ≥1 survey question in the pre and postintervention phases, respectively. Overall patient satisfaction did not differ between groups [OR for a 1-point increment in satisfaction score between post- vs pre-intervention groups = 1.05; 95% CI: 0.90-1.22; P = .51]. Compared to preintervention, postintervention respondents were more likely to report higher satisfaction with time available to talk with their physician (OR of a 1-point increase in individual question response = 1.29; 95% CI: 1.09-1.54; P = .004). Compared to preintervention, more physicians in the postintervention phase rated satisfaction with consent process efficiency as "very satisfied" or "satisfied" (P < .001). CONCLUSION: An informed consent video prior to colonoscopy resulted in similar overall patient satisfaction. However, post-intervention, patients were more likely to report sufficient time to talk with their physician, and physicians reported higher satisfaction with consent efficiency.

Unmet Needs in the Post-Direct-Acting Antiviral Era: Hepatocarcinogenesis After Hepatitis C Virus Eradication.

Infection with chronic hepatitis C virus (HCV) is an important risk factor for hepatocellular carcinoma (HCC). Direct-acting antiviral therapy has transformed care for patients with HCV and reduces the risk of HCC. Despite HCV cure, a residual HCC risk remains in patients with advanced fibrosis and cirrhosis, with multiple mechanisms underlying subsequent hepatocarcinogenesis. Transcriptomic and proteomic signatures demonstrate the capacity for HCC risk stratification, and chemoprevention strategies are emerging. For now, pending more precise stratification, HCC surveillance of patients with cured HCV and advanced fibrosis or cirrhosis should continue.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Serum Fibroblast Growth Factor-21 Discriminates Between Decompensated Alcohol-Associated Cirrhosis and Severe Alcohol-Associated Hepatitis.

INTRODUCTION: We hypothesized that fibroblast growth factor-21 (FGF-21) would be highly expressed in patients with alcohol-associated hepatitis (AH) and could be a novel and biologically relevant predictive biomarker to reliably distinguish severe AH and decompensated alcohol-associated cirrhosis (AC). METHODS: We identified a discovery cohort of 88 subjects with alcohol-associated liver disease (ALD) of varying disease severity from our ALD repository. Our validation cohort consisted of 37 patients with a biopsy-proven diagnosis of AH, AC, or absence of ALD with Model for End-Stage Liver Disease scores ≥10. Serum from both groups during index hospitalization was assayed for FGF-21 by ELISA. We performed receiver operating characteristic analysis and prediction modeling in both cohorts to discriminate between AH and AC in high Model for End-Stage Liver Disease (≥20) patients. RESULTS: In both cohorts, FGF-21 concentrations were highest in subjects with moderate to severe AH compared with those having alcohol use disorder or AC (mean: 2,609 pg/mL, P < 0.0001). The discovery cohort area under the curve of FGF-21 between AH and AC was 0.81 (95% confidence interval: 0.65-0.98, P < 0.01). In the validation cohort, FGF-21 levels were higher in severe AH compared with AC (3,052 vs 1,235 pg/mL, P = 0.03), and the area under the curve was 0.76 (95% confidence interval: 0.56-0.96, P < 0.03). A survival analysis showed that patients with FGF-21 serum levels in the second interquartile had the highest survival compared with all other quartiles. DISCUSSION: FGF-21 performs well as a predictive biomarker to distinguish severe AH from AC and may be helpful in the management and clinical investigation of patients with severe alcohol-associated liver diseases.

Psychotherapy for Alcohol Use Disorder Is Associated With Reduced Risk of Incident Alcohol-Associated Liver Disease.

BACKGROUND & AIMS: Alcohol-associated liver disease (ALD) is a devastating complication of alcohol use disorder (AUD). Once it develops, ALD is exceedingly difficult to treat; it therefore is critical to identify ways to prevent ALD. By treating the causes of increased alcohol consumption, psychotherapy may offer prophylactic benefit against the development of ALD for patients with AUD. METHODS: In this retrospective cohort study, we used International Classification of Diseases, 9th and 10th revision, codes to identify 9635 patients with AUD in the Mass General Brigham Biobank. The mean follow-up period from AUD diagnosis was 9.2 years. We used Cox regression models to generate hazard ratios (HR) for the development of ALD given the receipt or nonreceipt of psychotherapy, adjusting for a range of other contributors including the receipt of medication-assisted treatment. RESULTS: In our cohort, 60.4% of patients were men, 83.5% of patients were white, the median age was 57.0 years, and 3544 patients (36.8%) received psychotherapy. ALD developed in 1135 patients (11.8%). In multivariable analysis, psychotherapy was associated with a reduced rate of ALD (HR, 0.59; 95% CI, 0.50-0.71; P < .001). This association held for both individual psychotherapy (HR, 0.70; 95% CI, 0.56-0.86; P < .001) and group psychotherapy (HR, 0.76; 95% CI, 0.61-0.94; P = .01). Among patients with cirrhosis, psychotherapy was associated with a lower rate of hepatic decompensation (HR, 0.68; 95% CI, 0.48-0.95; P = .03). CONCLUSIONS: The receipt of psychotherapy in the setting of AUD is associated with reduced incidence and progression of ALD. Given the safety and potential benefit of psychotherapy, clinicians should consider using it to prevent the development of ALD.

Iron-biofortified pearl millet consumption increases physical activity in Indian adolescent schoolchildren after a 6-month randomised feeding trial.

Fe deficiency has negative effects on voluntary physical activity (PA); however, the impact of consuming Fe-biofortified staple foods on voluntary PA remains unclear. This study compared the effects of consuming Fe-biofortified pearl millet or a conventional pearl millet on measures of voluntary PA in Indian schoolchildren (ages 12-16 years) during a 6-month randomised controlled feeding trial. PA data were collected from 130 children using Actigraph GT3X accelerometers for 6 d at baseline and endline. Minutes spent in light and in moderate-to-vigorous PA were calculated from accelerometer counts using Crouter's refined two-regression model for children. Mixed regression models adjusting for covariates were used to assess relationships between intervention treatment or change in Fe status and PA. Children who consumed Fe-biofortified pearl millet performed 22·3 (95 % CI 1·8, 42·8, P = 0·034) more minutes of light PA each day compared with conventional pearl millet. There was no effect of treatment on moderate-to-vigorous PA. The amount of Fe consumed from pearl millet was related to minutes spent in light PA (estimate 3·4 min/mg Fe (95 % CI 0·3, 6·5, P = 0·031)) and inversely related to daily sedentary minutes (estimate -5·4 min/mg Fe (95 % CI -9·9, -0·9, P = 0·020)). Consuming Fe-biofortified pearl millet increased light PA and decreased sedentary time in Indian schoolchildren in a dose-dependent manner.

Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. METHODS: This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. RESULTS: NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. CONCLUSIONS: Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease.

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Iron status is associated with worker productivity, independent of physical effort in Indian tea estate workers.

Iron deficiency is the most common nutrient deficiency in the world, affecting roughly 40% of women in nonindustrialized countries. Iron is the essential element in hemoglobin, the major carrier of blood oxygen and oxidative metabolism that supports physical and cognitive performance. The relationship between iron and physical work capacity suggests that iron deficient individuals could experience reduced work output. Participants were 138 experienced tea pluckers aged 18-55 years from the Panighatta Tea Estate in Darjeeling District of northern West Bengal, India. Hemoglobin, serum ferritin, and soluble transferrin receptor were measured from venous blood. Energy expenditure was estimated from accelerometry and heart rate, and plucking productivity was measured as amount of tea plucked during the morning work session when temperature and rainfall conditions are optimal. At a given level of energy expenditure, iron deficient, anemic, and iron deficient anemic women plucked less tea during a 3-h period. The results warrant further research as to whether interventions providing supplemental iron might improve worker productivity and work efficiency. Further study should examine evidence of economic incentives for policies and programs targeting nutritional deficiencies. Novelty Anemia predicts up to 2.02 kg (9.1%) less tea plucked per 3 h, or 4.0% lower wage per 3 h, compared with nonanemic women, controlling for physical effort. An increase of 1.0 g/L in hemoglobin concentration predicts 0.71 kg (3.3%) more tea plucked over 3 h. An increase of 1.0 g/L in hemoglobin concentration predicts a 1.6% wage increase.

Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation in Children.

BACKGROUND: Despite high survival in pediatric living donor liver transplantation (LDLT), only 10% of liver transplants in children in the United States are from living donors, reflecting reluctance to embrace this approach. In addition to optimal timing and graft quality, LDLT may offer immunologic benefit because most donors are haploidentical parents. We sought to quantify the benefit of LDLT compared to deceased donor liver transplantation (DDLT) using granular clinical and immunologic outcomes over the long term. METHODS: A retrospective cohort of children (age <18 years) surviving 1 year or longer posttransplant was evaluated to determine the impact of donor type on graft survival and immunologic outcomes. RESULTS: Two hundred forty-one children (177 DDLT and 64 LDLT) were assessed. In multivariable analysis, LDLT was associated with a lower rate of acute cellular rejection (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98; P = 0.04), a lower rate of chronic rejection (HR, 0.12; 95% CI, 0.03-0.56; P = 0.007), better graft survival on monotherapy immunosuppression at 3 years posttransplant (87.7% vs 46.7%; odds ratio, 7.41; 95% CI, 2.80-19.66; P < 0.001), and a lower rate of graft loss (HR, 0.29; 95% CI, 0.10-0.88; P = 0.03). Graft type was not an independent predictor of posttransplant mortality (LDLT HR, 0.57; 95% CI, 0.16-2.01; P = 0.38). Maternal graft LDLT was associated with a lower rate of acute cellular rejection (HR, 0.13; 95% CI, 0.03-0.64; P = 0.01) and posttransplant lymphoproliferative disorder (HR, 0.04; 95% CI, 0.004-0.44; P = 0.008) compared with paternal grafts. CONCLUSIONS: This study demonstrates the potential benefit of LDLT, particularly with maternal grafts, for pediatric liver transplant recipients on multiple clinical parameters over long-term follow-up.

Leaning to the Left: Increasing the Donor Pool by Using the Left Lobe, Outcomes of the Largest Single-center North American Experience of Left Lobe Adult-to-adult Living Donor Liver Transplantation.

OBJECTIVE: Centers offering adult living donor liver transplantation (LDLT) mostly use right lobe grafts due to fears of providing recipients with insufficient hepatic volume, and the technical challenges presented by using left lobe grafts (LLGs). LLGs therefore represent approximately 5% of adult LDLTs performed in the United States. Here we present the largest North American experience with the use of LLG for adult LDLT. METHODS: Analysis of a prospectively maintained database of LDLTs performed from 1998 to 2015 at our institution. RESULTS: A total of 214 adult LDLTs were studied. Fifty-six patients (26%) received LLG. LLG recipients were more likely to be women, had significantly lower BMI, graft weight, and graft-weight-recipient-weight ratios (P < 0.05 for all). There were no significant differences in vascular or biliary complication between the groups. No significant differences existed in patient or graft survival at 1, 3, and 5 years (P = 0.747 and P = 0.398 respectively). Despite significantly increased risk of small-for-size syndrome in LLG, there was no increased risk of retransplant within 90-days or perioperative mortality in LLG recipients (P = 0.308 and P = 0.932 respectively). Graft type did not predict patient or graft outcomes on regression analysis (P = 0.857 and 0.399 respectively). CONCLUSIONS: Despite smaller graft sizes, outcomes of adult LDLT using LLG are comparable to right lobe grafts transplants. Left lobes can provide an important resource in an era of severe organ shortages, and these data should serve to allay the concerns of the transplant community in the United States.

A Randomized Trial of Iron-Biofortified Pearl Millet in School Children in India.

BACKGROUND: Iron deficiency is the most widespread nutritional deficiency in the world. OBJECTIVE: The objective of this randomized efficacy trial was to determine the effects of iron-biofortified pearl millet (Fe-PM) on iron status compared with control pearl millet (Control-PM). METHODS: A randomized trial of biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was conducted in 246 children (12-16 y) for 6 mo in Maharashtra, India. Iron status [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total body iron (TBI)], inflammation (C-reactive protein and α-1 acid glycoprotein), and anthropometric indices were evaluated at enrollment and after 4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe-PM on iron status compared with commercially available Control-PM. Linear and binomial regression models were used to evaluate the effects of Fe-PM on iron status and incidence of anemia and iron deficiency, compared with Control-PM. RESULTS: At baseline, 41% of children were iron deficient (SF <15 µg/L) and 28% were anemic (hemoglobin <12.0 g/dL). Fe-PM significantly increased SF concentrations and TBI after 4 mo compared with Control-PM. Among children who were iron deficient at baseline, those who received Fe-PM were 1.64 times more likely to become iron replete by 6 mo than were those receiving Control-PM (RR: 1.64, 95% CI: 1.07, 2.49, P = 0.02). The effects of Fe-PM on iron status were greater among children who were iron deficient at baseline than among children who were not iron deficient at baseline. CONCLUSIONS: Fe-PM significantly improved iron status in children by 4 mo compared with Control-PM. This study demonstrated that feeding Fe-PM is an efficacious approach to improve iron status in school-age children and it should be further evaluated for effectiveness in a broader population context. This trial was registered at clinicaltrials.gov as NCT02152150.