Nightshade Vegetables: A Dietary Trigger for Worsening Inflammatory Bowel Disease and Irritable Bowel Syndrome?

The Solanaceae family of plants, commonly known as Nightshade vegetables or Nightshades, contains a diverse range of crops of over 2000 members with significant culinary, economic, and cultural importance. Familiar edible Nightshades include tomatoes, peppers, eggplants, and white potatoes. Many pharmacologically active compounds used in traditional medicine, including atropine and hyoscyamine, are derived from Nightshades. In addition to these beneficial pharmacologic agents, Nightshade-derived glycoalkaloid compounds, a key defense mechanism against predation, have been shown to disrupt intestinal epithelium and to potentially activate mast cells in the gut mucosa, leading to adverse symptoms in humans. There is a new appreciation that mast cell activation is an allergic inflammatory mechanism contributing both to pain in irritable bowel syndrome (IBS) and to gut inflammation in inflammatory bowel disease (IBD). Given their ubiquity in Western diets and their shared glycoalkaloid active compounds, edible Nightshades are attracting new interest as a potential trigger for worsening gut symptoms in functional and inflammatory gastrointestinal disorders. Here, we review the limited existing literature on the adverse effects of Nightshade consumption, including the effects of Nightshade-derived glycoalkaloids on IBD gut inflammation, and the under-recognized contribution of Nightshades to food allergies and allergic cross-reactivity. We then highlight new evidence on the contributions of mast cell activation to GI disorder pathogenesis, including potential linkages between Nightshade antigens, intestinal mast cells, and GI dysfunction in IBS and IBD.

Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth.

There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.

Cannabis Use in Patients with Gastroparesis.

Aim: The primary aim was to determine the prevalence of cannabis use among patients hospitalized for gastroparesis. The secondary aim was to identify independent variables associated with cannabis use compared with noncannabis-related gastroparesis hospitalization. Methods: We use the nationwide inpatient sample database from January 2012 to December 2014. The patients included in this study were the ones with primary diagnosis of gastroparesis and cannabis use. The analysis was performed using the Statistical Package for the Social Sciences 27 (SPSS) and a multivariable regression was conducted to identify independent variables. Results: We found 50,170 patients with a primary diagnosis of gastroparesis. The prevalence of cannabis use among patients hospitalized for gastroparesis was 4.2%. Multivariate regression analysis was performed, adjusting for confounders. The variables found to increase the odds of cannabis use in gastroparesis populations independently were age interval of 18-35 and 36-50 years, male, Black and Asian, median household income 1-25th percentile, Medicaid insurance, no charge hospitalization, and smoking. Cannabis use was associated with lower odds of vomiting. Conclusion: Patients who used cannabis were younger and of African American, Asian, or Pacific Islander descent. They had Medicaid insurance and a lower median household income.

Gastric Electrical Stimulation for the Treatment of Gastroparesis or Gastroparesis-like Symptoms: A Systemic Review and Meta-analysis.

BACKGROUND: The effects of gastric electrical stimulation are not fully understood. We aimed to assess the efficacy of gastric electrical stimulation (GES) for patients with gastroparesis and gastroparesis-like symptoms. MATERIALS AND METHODS: We searched PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct to identify controlled trials and cohort studies. We used random effects models to estimate pooled effects. A total of nine studies met the criteria and were included for the final qualitative synthesis and the quantitative analysis. We examined the mean absolute differences (MD) and 95% CIs. RESULTS: Nine studies (n = 730) met the criteria and were included for the final qualitative synthesis and the quantitative analysis. There was significant improvement in gastrointestinal (GI) total symptom score (TSS) with the GES group compared with controls during the randomized blind trials. This effect was sustained at 12 months after treatment compared with before treatment (MD = -6.07; 95% CI, -4.5 to -7.65; p < 0.00001). The pooled effect estimate showed a significant improvement in frequency of weekly vomiting episodes at 12 months compared with before treatment (MD = -15.59; 95% CI, -10.29 to -20.9; p < 0.00001). CONCLUSION: GES appears beneficial, with significant improvement in GI TSS, weekly vomiting frequency, gastric emptying study, and quality of life.

Paravertebral anesthetic nerve block for pain control after peroral endoscopic myotomy.

BACKGROUND: Excess post-operative opioid medication use can delay recovery and is associated with long-term misuse, addiction, and overdose. We aimed to explore the effect of pre-procedural thoracic paravertebral nerve block (PNB) on pain-related outcomes after POEM. METHODS: In this retrospective cohort study, consecutive patients who did and did not receive a PNB prior to POEM were compared. The outcomes were peak and cumulative pain scores, total opioid use during hospitalization, and length of stay. After adjusting for confounders, the associations between nerve block and the outcomes of interest were explored. RESULTS: Forty-nine consecutive patients were enrolled; 25 patients received a block whereas the subsequent 24 did not. There were no differences in baseline characteristics between the study groups. In unadjusted analyses, there was no significant difference between patients who did and did not undergo PNB in peak pain score (7.8 vs. 8.7, p=0.14), cumulative pain score in the first 12 hours (area under curve 66.5 vs. 75.8, p=0.22), median total opioid use (38.9 mg morphine equivalent dosing vs. 42, p=1.00), and median length of hospitalization (26.5 hours vs. 24, p=0.35). In multivariable regression models, PNB was not associated with a reduction in pain scores, opioid use, or hospitalization. There were no adverse events related to the block. CONCLUSIONS: In this exploratory, observational study, paravertebral nerve block immediately before POEM did not result in a statistically significant reduction in pain-related outcomes or hospitalization. Additional observational studies may elucidate whether higher anesthetic doses or longer acting formulations would be of value.

A Coached Digital Cognitive Behavioral Intervention Reduces Anxiety and Depression in Adults With Functional Gastrointestinal Disorders.

INTRODUCTION: Traditional cognitive behavioral interventions (CBIs) improve mood and gastrointestinal symptom severity in patients with functional gastrointestinal disorders (FGIDs) but face substantial barriers to implementation. Integrating behavioral health technology into medical clinic workflows could overcome these barriers. We evaluated the feasibility and impact of a coached digital CBI (dCBI) as a first-line intervention in a prospective cohort of emotionally distressed patients with FGID. METHODS: Patients with anxiety and/or depressive symptoms were offered a dCBI (an app called RxWell) during routine clinic visits. RxWell provides cognitive behavioral techniques enhanced by within-app text messaging with a health coach. Both gastroenterology and behavioral health-care providers electronically prescribed RxWell. We tracked patient interactions with RxWell, and patients completed anxiety (General Anxiety Disorder-7) and depression (Personal Health Questionniare Depression Scale) measures through the app. Our primary study outcome was the change in General Anxiety Disorder-7 and Personal Health Questionniare Depression Scale scores. RESULTS: Of 364 patients with FGID (mean age 43 years [SD 16 years]; 73.1% women) prescribed the dCBI, 48.4% enrolled (median use, 3 techniques [interquartile range 1-14]). About half of RxWell enrollees communicated with health coaches. The mean baseline anxiety score was 11.4 (SD 5.5), and the depression score was 11.5 (SD 6.1). RxWell users experienced improvements in anxiety (mean change 2.71 [t = 3.7, df = 58; P < 0.001]) and depression (mean change 2.9 [t = 4.2, df = 45; P < 0.001]) at 4 months. DISCUSSION: Patients with FGIDs and moderately severe anxiety and depressive symptoms are willing to use dCBI tools recommended by their providers. Our pilot data demonstrate that dCBI usage is associated with clinically and statistically significant mood symptom reductions.

Characteristics of patients who underwent gastric electrical stimulation vs. surgical pyloric interventions for refractory gastroparesis.

BACKGROUND: There has been recent debate comparing the efficacy of gastric electrical stimulation (GES) with pyloric intervention, but medical literature lacks clear indications for when to perform GES or pyloric intervention. This study aims to assess the effect of sociodemographic factors and hospital characteristics on the surgical technique chosen for the treatment of gastroparesis. METHODS: Data was extracted from the National Inpatient Sample between the years 2012 and 2014, using any discharge diagnosis of gastroparesis. For comparison of analysis between GES and pyloric surgical intervention, pyloroplasty, endoscopic pyloric dilation, and pyloromyotomy were considered to be pyloric interventions. The study population was divided into two groups, one which received GES and the other receiving pyloric intervention, to compare socioeconomic factors and hospital characteristics. RESULTS: In total, 737,930 hospitalizations had a discharge diagnosis of gastroparesis between 2012 and 2014. On weighted multivariant analysis of patients undergoing GES or pyloric intervention for gastroparesis, being female (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.25-1.78; P < 0.001), being Hispanic (OR 1.75, 95%CI; P < 0.001), being in urban teaching (OR 1.41, 95%CI 1.15-1.72; P < 0.001), and nonteaching hospitals (OR 2.93, 95%CI 2.4-3.58; P < 0.001), early satiety (OR 6.70, 95%CI 1.54-31.25; P = 0.01), and diabetes mellitus (OR 2.14, 95%CI 1.78-2.56; P < 0.001) were each statistically significantly correlated with receiving GES intervention compared to pyloric intervention. CONCLUSION: The racial difference, payer source, and hospital location affected the surgical intervention (GES or pyloric intervention) that patients with gastroparesis would receive.

Incidence of Hepatocellular Carcinoma in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.

BACKGROUND: The risk and determinants of HCC in patients with primary biliary cholangitis (PBC) are unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and risk factors associated with HCC risk among patients with PBC. METHODS: We searched PubMed, EMBASE, MEDLINE, Cochrane databases and reference lists from relevant articles to identify cohort studies that examined incidence of HCC in patients with PBC from inception through November 2019. RESULTS: A total of 29 studies including 22,615 patients met the eligibility criteria. The median cohort size was 292 patients followed for an average of 76 months. The pooled incidence rate for patients with PBC was 4.17 per 1000 patient-years (95% CI 3.17-5.47). On subgroup analysis, the incidence of HCC in patients with PBC cirrhosis was 15.7 per 1000 patient-years (95% CI 8.73-28.24). The HCC incidence rate was 9.82 per 1000 person-years (95% CI 5.92-16.28) in men and 3.82 per 1000 person-years (95% CI 2.85-5.11) in women. CONCLUSIONS: Cirrhosis is the strongest risk factor for HCC in patients with PBC. Male gender was also a risk factor. Our meta-analysis supports current recommendations of HCC surveillance in patients with PBC cirrhosis. Further studies are needed to evaluate risk factors in this population.

Risk Trajectories for Readmission and Death After Cirrhosis-Related Hospitalization.

INTRODUCTION: Patients hospitalized for cirrhosis are at high risk for readmission and death for the first 30 days following discharge. However, there is no information on how these risks dynamically change over a full year after discharge. Our aim was to determine the absolute risks of first readmission and death and characterize these changes in the first year following hospital discharge. METHODS: We conducted a retrospective cohort study of patients who were hospitalized with cirrhosis at all Veterans Affairs hospitals and discharged home between 01/01/2010 and 12/31/2013. We used separate survival models to determine risk of first readmission and death after hospital discharge. We also examined the absolute daily risks for first readmission and death by day and identified the time required for risks of readmission and death to decline 50% and 75% from maximum values. RESULTS: Of the 38,955 patients who survived index hospitalization for cirrhosis, 23,318 patients (59.9%) had at least one readmission and 11,567 patients (29.7%) died within the first year. Daily risk of readmission was the highest on day 1 (1.23%) and declined 50% by day 71 and 75% by day 260. After 1 year, daily risk of readmission did not plateau. Daily risk of death was the highest on day 1 (0.78%) and declined 50% by day 31 and 75% by day 64. CONCLUSION: The risk of readmission and death after cirrhosis-related hospitalization remains elevated for prolonged periods. Patients and providers should remain vigilant for clinical health deterioration beyond the first 30 days following hospitalization.

Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US. We aimed to study the prevalence and risk factors associated with the development and short term mortality in a large cohort of patients in the US. METHODS: Using the US Department of Veterans Affairs (VA) Corporate Data Warehouse, we identified patients with ACLF during hospitalisation for decompensated cirrhosis at any of the 127 VA hospitals between January 1, 2004, and December 31, 2014. We examined the prevalence of ACLF and variables associated with 28- and 90-day mortality in ACLF, and trends in prevalence and survival over time. RESULTS: Of 72,316 patients hospitalised for decompensated cirrhosis, 19,082 (26.4%) patients met the criteria of ACLF on admission. Of these, 12.8% had 1, 10.1% had 2, and 3.5% had 3 or more organ failures. Overall, 25.5% and 40.0% of ACLF patients died within 28 days and 90 days of admission, respectively. Older age, White race, liver cancer, higher model for end-stage liver disease sodium corrected score, and non-liver transplant centre were associated with increased risk of death in ACLF. Over the study period, the prevalence of ACLF decreased, and all grades but ACLF-3 had improvement in survival. CONCLUSIONS: In a US cohort of hospitalised patients with decompensated cirrhosis, ACLF was common and associated with high short-term mortality. Over a decade, ACLF prevalence decreased but survival improvement of ACLF-3 was not seen. Early recognition and aggressive management including timely referral to transplant centres may lead to improved outcomes in ACLF. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is a condition marked by multiple organ failures in patients with cirrhosis and associated with a high risk of death. In this study of US patients hospitalised with cirrhosis, 1 in 4 patients developed ACLF. In total, 25% of patients with ACLF died within 1 month and 40% died within 3 months. Thus, early recognition of ACLF is important for the initiation of aggressive management, which is required to save these patients' lives.

Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI. METHODS: We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis. RESULTS: We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives). CONCLUSIONS: In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.

A Randomized Trial of Off-Site Collaborative Care for Depression in Chronic Hepatitis C Virus.

OBJECTIVE: To test the effectiveness of a collaborative depression care model in improving depression and hepatitis C virus (HCV) care. DATA SOURCES/STUDY SETTING: Hepatitis C virus clinic patients who screened positive for depression at four Veterans Affairs Hospitals. STUDY DESIGN: We compared off-site depression collaborative care (delivered by depression care manager, pharmacist, and psychiatrist) with usual care in a randomized trial. Primary depression outcomes were treatment response (≥50 percent decrease in 20-item Hopkins Symptoms Checklist [SCL-20] score), remission (mean SCL-20 score, <0.5), and depression-free days (DFDs). Primary HCV outcome was receipt of HCV treatment. DATA COLLECTION: Patient data were collected by self-report telephone surveys at baseline and 12 months, and from electronic medical records. PRINCIPAL FINDINGS: Baseline screening identified 292 HCV-infected patients with depression, and 242 patients completed 12-month follow-up (82.9 percent). Intervention participants were more likely to report depression treatment response, remission, and more DFDs than usual care participants. Intervention participants were more likely to receive antiviral treatment; however, the difference was not statistically significant. CONCLUSION: Off-site depression collaborative care improved depression outcomes in HCV patients and may serve as a model for collaboration between mental health and specialty physical health providers in other high co-occurring conditions.

Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In-Tube Test in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The QuantiFERON-Tuberculosis Gold In-Tube (QFT-GIT) (QIAGEN Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QFT-GIT test among patients with IBD. METHODS: We conducted a case-control study among eligible adults with QFT-GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary referral center from 2011 through 2013. We compared patients with IBD with indeterminate and determinate (positive or negative) results from the QFT-GIT test. We collected data on patient demographics, clinical features, laboratory parameters, and medication use from medical charts. We calculated odds ratios (OR) and 95% CIs using multivariate logistic regression models. RESULTS: A total of 400 patients with IBD (265 Crohn's disease and 135 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 11.5% of patients. At the time of testing, a higher proportion of patients with indeterminate results from the QFT-GIT test were on systemic corticosteroid therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had levels of C-reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear test results; P = .005), had an erythrocyte sedimentation rate above 15 mm/h (55.6% vs 35.8% of patients with clear test results; P = .01), had serum levels of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P < .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear test results; P = .001). In multivariable analysis, corticosteroid use (adjusted OR, 2.92; 95% CI, 1.44-5.88; P = .003) and serum levels of albumin below 3.5 g/dL (adjusted OR, 3.62; 95% CI, 1.36-9.60; P = .009) were independently associated with increased risk of indeterminate QFT-GIT test results. We did not identify a dose-related effect with corticosteroid therapy and the odds of indeterminate QFT-GIT test results. CONCLUSIONS: In a case-control study of patients with IBD, we associated systemic corticosteroid therapy and low levels of albumin with an increased likelihood of having indeterminate QFT-GIT test result.

Interchangeable Use of Proton Pump Inhibitors Based on Relative Potency.

Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.

Trends in 30-Day and 1-Year Mortality Among Patients Hospitalized With Cirrhosis From 2004 to 2013.

OBJECTIVES: Recent data suggest decreasing in-patient mortality in patients hospitalized with cirrhosis. We sought to determine if improvements in short-term outcomes for patients with cirrhosis are associated with changes in longer-term outcomes. METHODS: We examined temporal trends in 30 days and 1-year postdischarge mortality among patients hospitalized with cirrhosis at any of the 126 Veterans Administration hospitals from 2004 and 2013. We adjusted for a range of demographic, liver disease severity, and comorbidity-related factors to account for differences in patient cohorts over time. RESULTS: We identified 109,358 unique patients who were hospitalized with cirrhosis between 2004 and 2013. In-hospital mortality decreased from 11.4 to 7.6%, whereas 1-year mortality decreased from 34.5 to 33.2%. Over a third of out-of-hospital deaths occurred within the first 30 days after discharge; 30-day mortality increased from 9.3 to 10.1%. After adjusting for patient factors, the odds of in-hospital mortality in 2013 were 30% lower (adjusted odds ratio (OR)=0.70, 95% confidence interval (CI), 0.64-0.78), 1-year mortality were 13% lower (adjusted OR=0.87, 95% CI=0.82-0.93), whereas the 30-day mortality were 10% higher than 2004 (adjusted OR=1.10, 95% CI=0.99-1.21), although the latter did not reach statistical significance. CONCLUSIONS: In patients admitted with cirrhosis, reduction in in-hospital mortality was associated with less marked reduction in 1-year mortality, and an unchanged, if not higher, 30-day mortality following discharge. Our data suggest that some of the burden of mortality in cirrhosis has shifted from in-hospital to the immediate postdischarge period.

Incidence and Determinants of Hepatocellular Carcinoma in Autoimmune Hepatitis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta-analysis of the incidence of HCC and associated risk factors among patients with AIH. METHODS: We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis. The between-study heterogeneity was assessed using I2 statistic. RESULTS: A total of 25 studies (20 papers and 5 abstracts), including 6528 patients, met the eligibility criteria. The median cohort size was 170 patients with AIH (range, 25-1721 patients), followed for a median of 8.0 years (range, 3.3-16.0 years). The pooled incidence rate for HCC in patients with AIH was 3.06 per 1000 patient-years (95% confidence interval, 2.22-4.23; I2 = 51.5%; P = .002). The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 10.07 per 1000 patient-years (95% confidence interval, 6.89-14.70; I2 = 48.8%; P = .015). In addition, 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their HCC diagnosis. The risk of HCC seems to be lower in patients with AIH and cirrhosis than that reported for patients with cirrhosis from hepatitis B, hepatitis C, or primary biliary cholangitis. CONCLUSIONS: Based on the increased risked of HCC shown in this meta-analysis, there may be a role for HCC surveillance in patients with AIH and cirrhosis.