Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M

doi:10.4254/wjh.v8.i35.1547

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 8, Issue 35

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Supplementary Materials of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (10413)

All Articles published online

The chart showing PDF series, WORD series, HTML series, Figures (1-2) series, Tables (1-4) series.

Item

Count

PDF

388

WORD

298

HTML

4401

Figures (1-2)

154

Tables (1-4)

166

Sum=5407

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

664

Download

1045

Sum=1709

Publishing Process of This Article

Item

Count

Browse

1265

Download

2032

Sum=3297

Dec 18, 2016 (publication date) through Apr 24, 2024

Times Cited of This Article

Times Cited (20)

Journal Information of This Article

Publication Name

World Journal of Hepatology

ISSN

1948-5182

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Hepatol. Dec 18, 2016; 8(35): 1547-1556
Published online Dec 18, 2016. doi: 10.4254/wjh.v8.i35.1547

Table 1 Patient characteristics before and after alcohol withdrawal

Parameters	Before withdrawal(n = 521)	After withdrawal(n = 370)
Demographic characteristics
Male (%)	72.1
Age (yr)	50.2 ± 11.3
Risk factors
BMI (kg/m²)	25.2 ± 4.6
H/W ratio	1.0 ± 0.1
Alcohol consumption (g/d)	192.1 ± 139.7
Duration (yr)	19.9 ± 13.3
Smoker (%)	70.9
Diabetes (%)	10.0
Coronary heart disease (%)	5.1
RR (%)	34.5
Ascites (%)	9.0
F0 (%)	47.4
F1-2 (%)	17.1
F3 (%)	10.8
F4 (%)	24.7
Noninvasive parameters
Hepatic steatosis (0-3, US)	1.9 ± 0.9
Liver stiffness (kPa)	15.8 ± 21.1	12.6 ± 18.1
Laboratory parameters
AST (U/L)	101 ± 108	54 ± 48
ALT (U/L)	70 ± 79	52 ± 46
GGT (U/L)	398 ± 577	268 ± 360
AP (U/L)	109 ± 76	88 ± 55
Bilirubin (mg/dL)	1.3 ± 2.8	0.9 ± 2.3
Albumin (g/dL)	5.0 ± 6.0
INR	1.2 ± 3.4	1.2 ± 5.1
Urea (mg/dL)	22.6 ± 16.6	23.7 ± 12.5
Creatinine (mg/dL)	0.7 ± 0.3	0.8 ± 0.2
Hemoglobin (g/dL)	14.2 ± 2.2	13.8 ± 1.8
Platelets (/nL)	209 ± 87	215 ± 82
Glucose (mg/dL)	109.1 ± 36.4
HbA1C (%)	5.6 ± 1.0
Triglycerides (mg/dL)	195.7 ± 206.6
Cholesterol (mg/dL)	215.9 ± 58.2
HDL cholesterol (mg/dL)	72.3 ± 36.9
LDL cholesterol (mg/dL)	112.6 ± 45.6
Lipase (U/L)	63.6 ± 164.8	60.7 ± 56.3
Ferritin (ng/mL)	580.6 ± 650.5
CRP (mg/dL)	6.1 ± 15.9	7.1 ± 12.5

Data are presented as mean ± SD or in %. BMI: Body mass index; H/W ratio: Hip to waist ratio; RR: Hypertension; F: Fibrosis stage; AST: Aspartate transaminase; ALT: Alanine transaminase; GGT: Gamma-glutamyl-transpeptidase; AP: Alkaline phosphatase; INR: International normalized ratio (Prothrombin); HDL: High-density lipoprotein; LDL: Low-density lipoprotein; CRP: C-reactive protein; US: Ultrasound.

Table 2 Characteristics of alcoholic liver disease sub-cohorts (n = 521) based on genotype distribution of rs738409 polymorphism

Parameters	PNPLA3 CC (n = 204)	PNPLA3 CG (n = 274)	PNPLA3 GG (n = 43)	PNPLA3 CG + GG (n = 317)
Demographic characteristics
Patients (%)	39.2	52.6	8.2	60.8
Age (yr)	49.5 ± 11.0	50.7 ± 11.8	50.1 ± 9.7	50.7 ± 11.5
Risk factors
BMI (kg/m²)	25.4 ± 4.9	25.1 ± 4.5	25.6 ± 3.9	25.2 ± 4.4
H/W ratio	1.0 ± 0.1	1.0 ± 0.1	1.0 ± 0.1	1.0 ± 0.1
Alcohol consumption (g/d)	194.0 ± 136.1	190.8 ± 146.2	181.2 ± 116.1	189.4 ± 142.0
Duration (yr)	18.3 ± 13.3	20.9 ± 13.1	17.2 ± 14.2	20.4 ± 13.3
Smoker (1 = yes)	0.7 ± 0.4	0.7 ± 0.5	0.6 ± 0.5	0.7 ± 0.5
Diabetes (1 = yes)	0.1 ± 0.3	0.1 ± 0.3	0.0 ± 0.2	0.1 ± 0.3
Coronary heart disease (1 = yes)	0.1 ± 0.2	0.1 ± 0.3	0.0 ± 0.0	0.1 ± 0.3
Noninvasive parameters
Hepatic steatosis (0-3, US)	1.8 ± 0.9	2.0 ± 0.8	1.9 ± 0.8	2.0 ± 0.8
Liver stiffness (kPa)	13.1 ± 17.7	17.6 ± 23.0^a	17.2 ± 22.2	17.5 ± 22.9^a
Laboratory parameter
AST (U/L) before detox	95.2 ± 100.8	102.8 ± 111.4	113.1 ± 116.8	104.0 ± 111.9
AST (U/L) after detox	47.8 ± 32.9	52.6 ± 46.0	82.8 ± 89.5^a	56.2 ± 53.5
ALT (U/L) before detox	66.0 ± 59.4	71.9 ± 93.0	76.4 ± 60.4	72.5 ± 89.2
ALT (U/L) after detox	47.5 ± 35.9	52.4 ± 50.9	67.7 ± 55.0^a	54.2 ± 51.5
GGT (U/L) before detox	406.3 ± 572.2	365.9 ± 516.1	537.7 ± 869.6	389.6 ± 578.9
GGT (U/L) after detox	254.8 ± 290.9	261.7 ± 347.3	389.7 ± 671.6	276.9 ± 399.6
AP (U/L) before detox	105.5 ± 76.2	111.6 ± 75.8	112.7 ± 72.6	111.8 ± 75.3
AP (U/L) after detox	83.3 ± 45.1	90.5 ± 59.2	97.5 ± 68.4	91.3 ± 60.2
Bilirubin (mg/dL)	1.2 ± 2.8	1.4 ± 3.0	0.9 ± 1.1	1.3 ± 2.8
Albumin (g/dL)	4.7 ± 4.7	5.3 ± 7.2	4.5 ± 0.5	5.2 ± 6.7
INR	1.4 ± 5.4	1.0 ± 0.4	0.9 ± 0.2	1.0 ± 0.4
Urea	20.6 ± 10.8	24.6 ± 20.2^a	20.1 ± 9.9	24.0 ± 19.2^a
Creatinine	0.7 ± 0.2	0.7 ± 0.3	0.7 ± 0.2	0.7 ± 0.3
Hemoglobin (g/dL)	14.2 ± 1.8	14.2 ± 2.5	14.6 ± 2.0	14.2 ± 2.4
Platelets (/nL)	216.7 ± 92.7	201.1 ± 80.0^a	224.2 ± 91.4	204.5 ± 82.0
Glucose (mg/dL)	112.0 ± 46.2	107.7 ± 28.5	110.7 ± 34.6	108.1 ± 29.3
HbA1C (%)	5.6 ± 1.1	5.6 ± 0.8	5.8 ± 1.3	5.6 ± 0.9
Triglycerides (mg/dL)	190.6 ± 202.2	192.0 ± 205.8	240.9 ± 230.4	198.7 ± 209.6
Cholesterol (mg/dL)	219.9 ± 55.0	213.1 ± 61.1	222.9 ± 53.4	214.4 ± 60.1
HDL cholesterol (mg/dL)	73.2 ± 35.9	71.4 ± 37.6	75.6 ± 37.3	71.9 ± 37.5
LDL cholesterol (mg/dL)	113.5 ± 46.3	112.4 ± 45.5	118.0 ± 44.7	113.0 ± 45.3
Lipase (U/L)	48.5 ± 45.9	75.9 ± 216.5	45.3 ± 26.0	72.0 ± 202.7
Ferritin (ng/mL)	546.1 ± 611.6	599.6 ± 668.3	685.2 ± 708.2	610.8 ± 673.1
CRP (mg/dL)	4.7 ± 11.1	7.1 ± 18.9	6.0 ± 12.0	7.0 ± 18.1

Data are presented as mean ± SD or in %; significant paired T tests (^aP < 0.05) with CC. BMI: Body mass index; H/W ratio: Hip to waist ratio; AST: Aspartate transaminase; ALT: Alanine transaminase; GGT: Gamma-glutamyl-transpeptidase; AP: Alkaline phosphatase; INR: International normalized ratio (Prothrombin); HDL: High-density lipoprotein; LDL: Low-density lipoprotein; CRP: C-reactive protein; US: Ultrasound; PNPLA3: Adiponutrin.

Table 3 Risk factors associated with F4 cirrhosis

Factor	OR	95%CI	P value
PNPLA3 G (CG + GG)	1.295	0.787-2.131	> 0.05
Gender	0.855	0.496-1.475	> 0.05
Age	1.040	1.017-1.064	< 0.001
BMI	1.037	0.983-1.093	> 0.05

BMI: Body mass index; OR: Odds ratio; PNPLA3: Adiponutrin.

Table 4 Spearman rank correlation of PNPLA3 carrier status and liver stiffness with histological parameters

Parameter (n = 80)	PNPLA3 CC (n = 43)	PNPLA3 CG (n = 29)	PNPLA3 GG (n = 8)	Liver stiffness (kPa)
Steatohepatitis (score 0-2)	-0.163	-0.099	0.404^b	0.391^b
Microgranulomas (score 0-1)	-0.095	-0.139	0.357^b	0.387^b
Ballooning (score 0-2)	-0.221^a	0.020	0.319^b	0.516^b
Glycogenated nuclei (score 0-1)	-0.124	-0.080	0.316^b	0.335^b
Steatosis (score 0-3)	-0.125	-0.045	0.264^a	0.096
Lobular inflammation (score 0-3)	-0.142	-0.003	0.227^a	0.420^b
Megamitochondria (score 0-1)	-0.121	-0.005	0.198	0.278^b
Large lipogranulomas (score 0-1)	0.134	-0.238^a	0.145	0.144
Acidophil bodies (score 0-1)	-0.016	-0.072	0.133	0.285^b
Pericellular fibrosis (score 0-3)	-0.224	0.141	0.131	0.567^b
Chevallier fibrosis score (SSS)	-0.189	0.112	0.131	0.828^b
Ballooning k8/18 stain (score 0-2)	-0.537^b	0.490^b	0.089	0.692^b
Kleiner fibrosis score (score 0-4)	-0.163	0.148	0.035	0.745^b
Mallory Denk Bodies (score 0-1)	-0.121	0.110	0.026	0.530^b
Apoptosis M30 stain (score 0-3)	-0.039	0.031	0.014	0.490^b
Pigmented macrophages (score 0-1)	0.003	0.012	-0.022	-0.009
Portal inflammation (score 0-1)	-0.027	0.099	-0.106	0.427^b
Liver stiffness (kPa)	-0.045	0.017	0.037	1.000

Liver stiffness primarily correlates with fibrosis and liver damage but not significant with steatosis. In contrast, GG carrier status is tightly associated with liver injury and weakly with steatosis.

^aP < 0.05 vs

^bP < 0.01. PNPLA3: Adiponutrin.

Citation: Rausch V, Peccerella T, Lackner C, Yagmur E, Seitz HK, Longerich T, Mueller S. Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148M. World J Hepatol 2016; 8(35): 1547-1556
URL: https://www.wjgnet.com/1948-5182/full/v8/i35/1547.htm
DOI: https://dx.doi.org/10.4254/wjh.v8.i35.1547