Ranjeeta Bahirwani M.D.

Sarmast, N., G. O. Ogola, M. Kouznetsova, M. Leise, R. Bahirwani, R. Maiwall, E. Tapper, J. Trotter, J. Bajaj, L. R. Thacker, P. Tandon, F. Wong, R. Reddy, J. G. O’Leary, A. Masica, A. M. Modrykamien, P. S. Kamath and S. K. Asrani (2020). “Model for End-stage Liver Disease-Lactate and Prediction of Inpatient Mortality in Patients with Chronic Liver Disease.” Hepatology Feb 21. [Epub ahead of print].

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BACKGROUND & AIMS: As compared to other chronic diseases, patients with chronic liver disease (CLD) have significantly higher inpatient mortality; accurate models to predict inpatient mortality are lacking. Serum lactate (LA) may be elevated in patients with CLD due to both tissue hypoperfusion as well as decreased lactate clearance. We hypothesized that a parsimonious model consisting of Model for End-stage Liver Disease (MELD) and LA at admission may predict inpatient mortality in patients with CLD. APPROACH & RESULTS: We examined all CLD patients in two large and diverse healthcare systems in Texas (North Texas, NTX and Central Texas, CTX) between 2010-2015. We developed (n=3,588) and validated (n=1,804) a model containing MELD and LA measured at time of hospitalization. We further validated the model in a second cohort of 14 tertiary care hepatology centers that prospectively enrolled non-elective hospitalized patients with cirrhosis (n=726). MELD-LA was an excellent predictor of inpatient mortality in development (c-statistic =0.81, 95% CI 0.79-0.82) and both validation cohorts (CTX cohort, c=0.85, 95% CI 0.78-0.87; multicenter cohort c=0.82, 95% CI 0.74-0.88). MELD-LA performed especially well in patients with specific cirrhosis diagnoses (c=0.84, 95% CI 0.81-0.86) or sepsis (c=0.80, 95% CI 0.78-0.82). For MELD score 25, inpatient mortality was 11.2% (LA=1 mmol/L), 19.4% (LA=3 mmol/L), 34.3% (LA=5 mmol/L) and >50% (LA >8 mmol/L). A linear increase (p<0.01) was seen in MELD-LA and increasing number of organ failures. Overall, use of MELD-LA improved the risk prediction in 23.5% of the patients as compared to MELD model alone. CONCLUSION: MELD-LA is an early and objective predictor of inpatient mortality and may serve as a novel model for risk assessment and guide therapeutic options.

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2019). “A Model for Glomerular Filtration Rate Assessment in Liver Disease (GRAIL) in the Presence of Renal Dysfunction.” Hepatology 69(3): 1219-1230.

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR < 30 mL/min/1.73 m(2) . Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001-2015). GRAIL had less bias and was more accurate and precise as compared with CKD-EPI, MDRD-4, and MDRD-6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m(2) as compared with CKD-EPI: 8.70 (18.24) mL/min/1.73 m(2) , MDRD-4: 8.82 (17.38) mL/min/1.73 m(2) , and MDRD-6: 6.53 (14.42) mL/min/1.73 m(2) . Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m(2) versus 36.1% (CKD-EPI), 36.1% (MDRD-4), and 52.8% (MDRD-6) (P < 0.01). An eGFR < 30 mL/min/1.73 m(2) by GRAIL predicted development of CKD (26.9% versus 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% versus 22.0% CKD-EPI versus 23.1% MDRD-4 versus 48.3% MDRD-6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Alsahhar, J. S., R. Idriss and R. Bahirwani (2019). “A Rare Case of Cutaneous Metastases Secondary to Hepatocellular Carcinoma.” Clin Gastroenterol Hepatol 17(3): e17.

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A 54-year-old man presented with a 2-month history of an abdominal rash, initially small papules over the epigastrium that spread medially and subsequently becoming painful. His past medical history included decompensated hepatitis C cirrhosis with hepatocellular carcinoma (HCC) BCLC stage B diagnosed 1 year before presentation (3 lesions, largest measuring 5 cm). He underwent chemoembolization followed by cyberknife radiation 6 months before the current presentation. Physical examination revealed a Sister Mary Joseph nodule surrounded by erythematous tender subcutaneous nodules. His serum α-fetoprotein was 1000 ng/mL. Given the high suspicion for metastases, punch biopsy of a nodule was performed revealing anastomosing cords of highly atypical cells with enlarged hyperchromatic pleomorphic nuclei and atypical mitoses, consistent with high-grade adenocarcinoma of hepatobiliary origin. The patient died of liver failure 2 weeks after presentation. Extrahepatic metastases occur in up to a third of HCC cases, lung being the most common metastatic site. Metastases to skin are rare , primarily occurring because of direct seeding of the tumor at sites of biopsies or biliary drains. Our case highlights an atypical presentation of HCC cutaneous metastases and the importance of biopsy to differentiate HCC from other malignancies with similar presentations. (Text of this image study, p. e17.)

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2018). “A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction.” Hepatology Oct 19. [Epub ahead of print].

Full text of this article.

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in presence of renal dysfunction. We developed a model for GFR Assessment In Liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction. Measured GFR (mGFR) by iothalamate clearance (n=12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR<30ml/min/1.73m(2) . Prediction of development of chronic kidney disease (mGFR < 20ml/min/1.73m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n=785) and external validation (n=68,217, 2001-2015). GRAIL had less bias, was more accurate and precise as compared to CKD-EPI, MDRD-4 and MDRD-6 at time points before/after LT for low GFR. For mGFR<30ml/min/1.73m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 [9.65] ml/min/1.73m(2) as compared to CKD-EPI: 8.70 [18.24]ml/min/1.73m(2) , MDRD-4: 8.82 [17.38]ml/min/1.73m(2) , and MDRD-6: 6.53[14.42] ml/min/1.73m(2) . Prior to LT, GRAIL correctly classified 75% as having mGFR<30ml/min/1.73m(2) vs. 36.1% (CKD-EPI), 36.1%(MDRD-4), and 52.8%(MDRD-6).(p<0.01) An eGFR<30ml/min/1.73m(2) by GRAIL predicted development of CKD (26.9% vs. 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% vs. 22.0% CKD-EPI vs. 23.1% MDRD-4 vs. 48.3% MDRD-6, p<0.01) in national data within 5 years after LT. CONCLUSION: GRAIL may serve as an alternative model to estimate GFR amongst patients with liver disease before and after LT at low GFR.

Alsahhar, J. S., R. Idriss and R. Bahirwani (2018). “A Rare Case of Cutaneous Metastases Secondary To Hepatocellular Carcinoma.” Clin Gastroenterol Hepatol. Jan 15. [Epub ahead of print].

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A 54-year-old man presented with a 2-month history of an abdominal rash, initially small papules over the epigastrium that spread medially and subsequently becoming painful. His past medical history included decompensated hepatitis C cirrhosis with hepatocellular carcinoma (HCC) CLC stage B diagnosed one year prior to presentation (3 lesions, largest measuring 5 cm). He underwent chemoembolization followed by cyberknife radiation 6 months prior to current presentation. Physical examination revealed a Sister Mary Joseph’s nodule surrounded by erythematous tender subcutaneous nodules (Figure a). His serum alpha-fetoprotein (AFP) was 1000 ng/ml. Given the high suspicion for metastases, punch biopsy of a nodule was performed revealing anastomosing cords of highly atypical cells with enlarged hyper-chromatic pleomorphic nuclei and atypical mitoses, consistent with high grade adenocarcinoma of hepatobiliary origin (Figure b+c). The patient died of liver failure two weeks after presentation. [Excerpt from text.]