Browsing by Author "Vuppalanchi, Raj"
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Item Assessment and management of comorbidities (including cardiovascular disease) in patients with nonalcoholic fatty liver disease(Wiley, 2012-09-25) Corey, Kathleen E.; Vuppalanchi, Raj; Medicine, School of MedicineNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Nonalcoholic steatohepatitis, the progressive form of NAFLD, can lead to end‐stage liver disease and hepatocellular carcinoma. However, the consequences of NAFLD are not confined to the liver. NAFLD is associated with an increased risk of cardiovascular disease (CVD) and is frequently associated with metabolic syndrome. Thus, there is a pressing need for the diagnosis and management of the comorbidities of NAFLD, including CVD. This review will guide clinicians in the assessment and management of metabolic disease and CVD in patients with NAFLD.Item Behaviors, symptoms, and outcomes of North American patients with autoimmune hepatitis during the COVID-19 pandemic(BMJ, 2021-12) Vuppalanchi, Vahin; Gelow, Kayla; Vuppalanchi, Raj; Lammert, Craig; Green, Kelsey; Medicine, School of MedicineThe management of patients with autoimmune hepatitis (AIH) in the era of SARS-CoV-2 is challenging given minimal published clinical data. We used a large cohort of patients with AIH across the USA to investigate the differences in known risk factors for severe SARS-CoV-2 and AIH characteristics among patients who experienced symptoms consistent with COVID-19 illness versus those who did not. Additionally, we explored the effect of living through the SARS-CoV-2 pandemic on the extrahepatic symptoms and behaviors of patients with AIH. An invitation to complete a COVID-19-specific questionnaire was publicized in well-established social media cohorts of patients with AIH. Eligibility criteria were age ≥18 years, US residency, and an AIH diagnosis by a physician. A total of 420 individuals were eligible for the study. Symptoms consistent with COVID-19 were reported in 11% (n=48) with 3 patients requiring hospitalizations. Body mass index (BMI) >40 kg/m2 (23% vs 10%, p=0.01) and exposure to house (33% vs 3%, p=0.0001) or work (38% vs 17%, p=0.02) contacts with COVID-19 were factors found higher in those with symptoms. Cirrhosis or steroid use or immunosuppression was not significantly different between symptomatic and non-symptomatic groups. Worsening fatigue (45% vs 30%, p=0.06), anxiety (89% vs 70%, p=0.08), and itch (40% vs 18%, p=0.03) were more common among those reporting COVID-19 symptoms compared with those without. BMI >40 kg/m2 and exposure to contacts with COVID-19 illness but not cirrhosis or immunosuppression were associated with increased risk of COVID-19 illness in patients with AIH.Item Cannabidiol (CBD) Consumption and Perceived Impact on Extrahepatic Symptoms in Patients with Autoimmune Hepatitis(Springer, 2019-07-30) Mathur, Karan; Vuppalanchi, Vahin; Gelow, Kayla; Vuppalanchi, Raj; Lammert, Craig; Medicine, School of MedicineBackground and Aims Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile. Methods An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey. Results In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations. Conclusion CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms.Item Clinical and histologic features of azithromycin-induced liver injury(Elsevier, 2015-02) Martinez, Melissa A.; Vuppalanchi, Raj; Fontana, Robert J.; Stolz, Andrew; Kleiner, David E.; Hayashi, Paul H.; Gu, Jiezhun; Hoofnagle, Jay H.; Chalasani, Naga; Department of Medicine, IU School of MedicineBACKGROUND & AIMS: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. METHODS: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6-month outcomes were examined. RESULTS: Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. CONCLUSIONS: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (ClinicalTrials.gov identifier, NCT00345930).Item Cost Effectiveness of Different Strategies for Detecting Cirrhosis in Patients With Non-alcoholic Fatty Liver Disease Based on United States Health Care System(Elsevier, 2020) Vilar-Gomez, Eduardo; Lou, Zhouyang; Kong, Nan; Vuppalanchi, Raj; Imperiale, Thomas F.; Chalasani, Naga; Medicine, School of MedicineBackground & Aims Several strategies are available for detecting cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD), but their cost effectiveness is not clear. We developed a decision model to quantify the accuracy and costs of 9 single or combination strategies, including 3 noninvasive tests (fibrosis-4 [FIB-4], vibration controlled transient elastography [VCTE], and magnetic resonance elastography [MRE]) and liver biopsy, for detection of cirrhosis in patients with NAFLD. Methods Data on diagnostic accuracy, costs, adverse events, and cirrhosis outcomes over a 5-y period were obtained from publications. The diagnostic accuracy, per-patient cost per correct diagnosis of cirrhosis, and incremental cost-effectiveness ratios (ICER) were calculated for each strategy for base cirrhosis prevalence values of 0.27%, 2%, and 4%. Results The combination of the FIB-4 and VCTE identified patients with cirrhosis in NAFLD populations with a 0.27%, 2%, and 4% prevalence of cirrhosis with the lowest cost per person ($401, $690, and $1024, respectively) and highest diagnostic accuracy (89.3%, 88.5%, and 87.5% respectively). The combination of FIB-4 and MRE ranked second in cost per person ($491, $781, and $1114, respectively) and diagnostic accuracy (92.4%, 91.6%, 90.6%, respectively). Compared to the combination of FIB-4 and VCTE (least costly), the ICERs were lower for the combination of FIB-4 and MRE ($2864, $2918, and $2921) than the combination of FIB-4 and liver biopsy ($4454, $5156, and $5956) at the cirrhosis prevalence values tested. When goal was to avoid liver biopsy, FIB-4+VCTE and FIB-4+MRE had similar diagnostic accuracies, ranging from 87.5% to 89.3% and 90.6% to 92.4% for cirrhosis diagnosis, although FIB-4+MRE had a slightly higher cost. Conclusions In our cost effectiveness analysis based on United States health care system, we found that results from FIB-4, followed by either VCTE, MRE, or liver biopsy, detect cirrhosis in patients with NAFLD with a high level of accuracy and low cost. Compared to FIB-4 + VCTE which was the least costly strategy, FIB-4+MRE had lower ICER than FIB-4+LB.Item Development and Validation of Model Consisting of Comorbidity Burden to Calculate Risk of Death Within 6 months for Patients With Suspected Drug-Induced Liver Injury(Elsevier, 2019-11) Ghabril, Marwan; Gu, Jiezhun; Yoder, Lindsay; Corbito, Laura; Ringel, Amit; Beyer, Christian D.; Vuppalanchi, Raj; Barnhart, Huiman; Hayashi, Paul H.; Chalasani, Naga; Medicine, School of MedicineBackground & Aims: Patients with drug-induced liver injury (DILI) frequently have comorbid conditions, but the effects of non-liver comorbidities on outcome is not well understood. We investigated the association between co-morbidity burden and outcomes of patients with DILI, and developed and validated a model to calculate risk of death within 6 months. Methods: A multiple logistic regression model identified variables independently associated with death within 6 months of presenting with suspected DILI (6-month mortality) for 306 patients enrolled in the DILIN prospective study at Indiana University (discovery cohort). The model was validated using data from 247 patients with suspected DILI enrolled in the same study at the University of North Carolina (validation cohort). Medical comorbidity burden was calculated using the Charlson comorbidity index—patients with scores higher than 2 were considered to have significant comorbidities. Results: Six-month mortality was 8.5% in the discovery cohort and 4.5% in the validation cohort. In the discovery cohort, significant comorbidities (odds ratio [OR], 5.4; 95% CI 2.1 – 13.8), model for end-stage liver disease score (OR, 1.11; 95% CI, 1.04–1.17), and serum level of albumin at presentation (OR, 0.39; 95% CI, 0.2–0.76) were independently associated with 6-month mortality. A model based on these 3 variables identified patients who died within 6 months with c-statistic values of 0.89 (95% CI, 0.86–0.94) in the discovery cohort and 0.91 (95% CI, 0.83–0.99) in the validation cohort. We developed a web-based calculator to determine risk of death within 6 months for patients with suspected DILI for use in the clinic. Conclusions: We developed and validated a model based on comorbidity burden, model for end-stage liver disease score, and serum level of albumin that predicts 6-month mortality in patients with suspected DILI.Item Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension(Elsevier, 2020-04) Chalasani, Naga; Abdelmalek, Manal F.; Garcia-Tsao, Guadalupe; Vuppalanchi, Raj; Alkhouri, Naim; Rinella, Mary; Noureddin, Mazen; Pyko, Maxmillan; Shiffman, Mitchell; Sanyal, Arun; Allgood, Adam; Shlevin, Harold; Horton, Rex; Zomer, Eliezer; Irish, William; Goodman, Zachary; Harrison, Stephen A.; Traber, Peter G.; Medicine, School of MedicineBackground & Aims Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies. We performed a phase 2b, randomized trial of the safety and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension. Methods Patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) from 36 centers were randomly assigned, in a double-blind manner, to groups that received biweekly infusions of belapectin 2 mg/kg (n = 54), 8 mg/kg (n = 54), or placebo (n = 54) for 52 weeks. The primary endpoint was change in HVPG (Δ HVPG) at the end of the 52-week period compared with baseline. Secondary endpoints included changes in liver histology and development of liver-related outcomes. Results We found no significant difference in ΔHVPG between the 2 mg/kg belapectin group and placebo group (–0.28 mm HG vs 0.10 mm HG, P = 1.0) or between the 8 mg/kg belapectin and placebo group (–0.25 mm HG vs 0.10 mm HG, P = 1.0). Belapectin had no significant effect on fibrosis or nonalcoholic fatty liver disease activity score, and liver-related outcomes did not differ significantly among groups. In an analysis of a subgroup of patients without esophageal varices at baseline (n = 81), 2 mg/kg belapectin was associated with a reduction in HVPG at 52 weeks compared with baseline (P = .02) and reduced development of new varices (P = .03). Belapectin (2 mg/kg) was well tolerated and produced no safety signals. Conclusions In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with significant reduction in HVPG or fibrosis compared with placebo. However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce HVPG and development of varices.Item Eight‐Fold Increase in Dietary Supplement–Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States(Wiley, 2022-02) Ghabril, Marwan; Ma, Jiayi; Patidar, Kavish R.; Nephew, Lauren; Desai, Archita P.; Orman, Eric S.; Vuppalanchi, Raj; Kubal, Shekhar; Chalasani, Naga; Medicine, School of MedicineWe investigated the trends in listing and outcomes of drug-induced acute liver failure (DIALF) over the last quarter century in the United States using the United Network for Organ Sharing (UNOS) database. We examined waitlisted patients in the UNOS database between 1995 and 2020 with a diagnosis of DIALF and assessed trends in etiologies, demographic and clinical characteristics, and outcomes over 3 periods: 1995-2003, 2004-2012, and 2013-2020. Patients with DIALF and cirrhosis were classified as drug-induced acute-on-chronic liver failure. Implicated agents including acetaminophen (APAP) and herbal or dietary supplements (HDSs) were ascertained. There were 2146 individuals with DIALF during the study period. The observed demographic trends between the earliest and latest period included fewer pediatric patients (18.8% to 13.5%) but with an increasing number of males in non-APAP DIALF (31.8% to 41.4%) and increased racial diversity in APAP DIALF. Antimicrobials remained the most common non-APAP agents across all periods, but antiepileptics, propylthiouracil, and mushroom poisoning decreased, while HDSs markedly increased from 2.9% to 24.1% of all non-APAP DIALF patients. The overall 5-year post-liver transplantation (LT) patient survival improved significantly over the 3 periods (69.9% to 77.4% to 83.3%) and was evident for both APAP and non-APAP DIALF. Over the last quarter century, there has been an 8-fold increase in HDS-related liver failure necessitating waitlisting for liver transplantation in the United States. There are other important temporal trends during the study period, including improved survival following LT among both APAP and non-APAP DIALF patients.Item Enhanced Liver Fibrosis Score Can Be Used to Predict Liver-Related Events in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis(Elsevier, 2020) Are, Vijay S.; Vuppalanchi, Raj; Vilar-Gomez, Eduardo; Chalasani, Naga; Medicine, School of MedicineItem Faecal Microbiota Transplantation plus selected use of antibiotics for severe-complicated Clostridium difficile infection: description of a protocol with high success rate(Wiley, 2015-08) Fischer, Monika; Sipe, Brian W.; Rogers, Nicholas A.; Cook, Gwen K.; Robb, Bruce W.; Vuppalanchi, Raj; Rex, Douglas K.; Department of Medicine, IU School of MedicineBackground Severe and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality. Aim To evaluate safety and efficacy of a sequential faecal microbiota transplantation (FMT) and antibiotic protocol in severe and severe/complicated CDI patients who are at high risk for colectomy. Methods All patients with severe and severe/complicated CDI refractory to oral vancomycin ± rectal vancomycin and intravenous metronidazole therapy were offered FMT. Treatment consisted of sequential FMTs via colonoscopy with the need for repeat FMT and continued vancomycin guided by clinical response and pseudomembranes at colonoscopy. Results A total of 29 patients underwent FMT between July 2013 and August 2014. The overall treatment response of endoscopic sequential FMT was 93% (27/29), with 100% (10/10) for severe CDI and 89% (17/19) for severe/complicated CDI. A single FMT was performed in 62%, two FMTs were performed in 31% and three FMTs in 7% of patients. The use of non-CDI antibiotics predicted repeat FMT (odds ratio = 17.5). The 30-day all-cause mortality after FMT was 7%, and the cumulative 3-month survival was 76%. Of the two patients who died within 30 days, one underwent colectomy and succumbed to sepsis; the other died from septic shock related to CDI. Conclusion The success of a treatment protocol for severe and severe/complicated involving faecal microbiota transplantation and continued vancomycin in selected patients was high, and it warrants further evaluation.