1.Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index for Classification of Patients with Steatotic Liver Disease
Akash ROY ; Arka DE ; Anand V. KULKARNI ; Surabhi JAJODIA ; Usha GOENKA ; Awanish TEWARI ; Nikhil SONTHALIA ; Mahesh K. GOENKA
Journal of Obesity & Metabolic Syndrome 2024;33(3):222-228
Background:
Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum.
Methods:
In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled.Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140–350 g/week (or 20– 50 g/day) for females and 210–420 g/week (or 30–60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated.
Results:
Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, –3.7 [IQR, –7 to –1.6]; MetALD, – 1.45 [IQR, –2.4 to 0.28]; and AALD, 0.71 [IQR, –1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <–3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >–1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff = 0.004; P= 0.33).
Conclusion
AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.
2.Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index for Classification of Patients with Steatotic Liver Disease
Akash ROY ; Arka DE ; Anand V. KULKARNI ; Surabhi JAJODIA ; Usha GOENKA ; Awanish TEWARI ; Nikhil SONTHALIA ; Mahesh K. GOENKA
Journal of Obesity & Metabolic Syndrome 2024;33(3):222-228
Background:
Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum.
Methods:
In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled.Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140–350 g/week (or 20– 50 g/day) for females and 210–420 g/week (or 30–60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated.
Results:
Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, –3.7 [IQR, –7 to –1.6]; MetALD, – 1.45 [IQR, –2.4 to 0.28]; and AALD, 0.71 [IQR, –1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <–3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >–1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff = 0.004; P= 0.33).
Conclusion
AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.
3.Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index for Classification of Patients with Steatotic Liver Disease
Akash ROY ; Arka DE ; Anand V. KULKARNI ; Surabhi JAJODIA ; Usha GOENKA ; Awanish TEWARI ; Nikhil SONTHALIA ; Mahesh K. GOENKA
Journal of Obesity & Metabolic Syndrome 2024;33(3):222-228
Background:
Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum.
Methods:
In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled.Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140–350 g/week (or 20– 50 g/day) for females and 210–420 g/week (or 30–60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated.
Results:
Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, –3.7 [IQR, –7 to –1.6]; MetALD, – 1.45 [IQR, –2.4 to 0.28]; and AALD, 0.71 [IQR, –1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <–3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >–1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff = 0.004; P= 0.33).
Conclusion
AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.
4.Downstaging with atezolizumab-bevacizumab: a case series
Anand V. KULKARNI ; Parthasarathy KUMARASWAMY ; Balachandran MENON ; Anuradha SEKARAN ; Anuhya RAMBHATLA ; Sowmya IYENGAR ; Manasa ALLA ; Shantan VENISHETTY ; Sumana Kolar RAMACHANDRA ; Giri V. PREMKUMAR ; Mithun SHARMA ; P. Nagaraja RAO ; Duvvur Nageshwar REDDY ; Amit G. SINGAL
Journal of Liver Cancer 2024;24(2):224-233
Background:
s/Aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown.
Methods:
In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging.
Results:
Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection.
Conclusions
Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.
5.The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Cheng Han NG ; Kai En CHAN ; Yip Han CHIN ; Rebecca Wenling ZENG ; Pei Chen TSAI ; Wen Hui LIM ; Darren Jun Hao TAN ; Chin Meng KHOO ; Lay Hoon GOH ; Zheng Jye LING ; Anand KULKARNI ; Lung-Yi Loey MAK ; Daniel Q HUANG ; Mark CHAN ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J. SANYAL ; Mark MUTHIAH
Clinical and Molecular Hepatology 2022;28(3):565-574
Background/Aims:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods:
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results:
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.