Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis

Table 1 Characteristics of the studies

Ref.	Year	Patients number	Country	Mean age (yr)	Male		Study design	Etiology	Median follow-up time (mo)	Endpoint event	MELD score/Child-Pugh score (Non-T2DM vs T2DM)	Glucose regulation o
Bianchi et al[14]	1994	382	Italy	54.6		229	Retrospective cohort	Alcohol, HBV, PBC, autoimmune, and cryptogenic	37	Mortality	Child-Pugh score: 7.31 ± 2.28 vs 7.35 ± 2.20 (P > 0.05)	Not described
Quintana et al[5]	2011	110	Mexico	56.6		57	Prospective cohort	Alcohol, HBV, HCV, autoimmunity, and cryptogenic	41	Mortality	MELD score: 10.3 ± 3.7 vs 11.9 ± 4.7 (P = 0.07)	Not described
Ahn et al[4]	2020	8631	Australia	Not mentioned		5813	Retrospective cohort	Alcohol, cryptogenic, NAFLD, HBV, metabolic liver disease, autoimmune liver disease, inflammatory liver disease, and unspecified	24	Mortality	Not described	Not described
										Ascites
										Gastrointestinal bleeding
										Hepatic encephalopathy
										SBP
										HCC
Wlazlo et al[6]	2013	226	Netherlands	59.2		129	Retrospective cohort	Alcoholic, NASH, viral, autoimmune, and others	74.4	Mortality	MELD score: 12.2 ± 7.5 vs 11.8 ± 7.3 (P = 0.681)	Median non-fasting glucose of 9.8 mmol/L
										SBP
Holstein et al[10]	2002	52	Germany	58.3		Not mentioned	Prospectively cohort	Alcohol, hepatitis C, hepatitis B, cryptogenic, primary biliary cirrhosis, hemosiderosis, and hemochromatosis	42	Mortality	Child-Pugh score: 44% of patients had stage A cirrhosis, 37% had stage B, and 19% had stage C	Basal C-peptide of 1.66 ± 0.85 nmol/L
Liu et al[8]	2016	72731	United States	Not mentioned		39065	Retrospective cohort	Alcoholic, nonalcoholic, and biliary	18	Ascites	Not described	Not described
										Gastrointestinal bleeding
										Hepatic encephalopathy
										SBP
										HCC
Ioannou et al[19]	2007	2120	United States	Not mentioned		2069	Retrospective cohort	HBV, HCV, alcohol, and others	43.4	HCC	Not described	Not described
N’kontchou et al[20]	2006	771	France	61.4		431	Retrospective cohort	HCV and alcoholic cirrhosis	50.4	HCC	Not described	Not described
Wang et al[12]	2020	207	China	53.1		140	Retrospective cohort	Not described	6	Gastrointestinal rebleeding	MELD score: 7.22 ± 3.98 vs 8.29 ± 2.35 (P = 0.141)	Not described
Nishida et al[15]	2006	56	Japan	41		34	Prospective cohort	HBV, HCV, alcohol, and unknown	44	Mortality	Child-Pugh score: 6.8 ± 2.4 vs 6.9 ± 2.3 (P > 0.05)	HbA1c (%) of 5.6 ± 1.6%
Yang et al[17]	2016	739	United States	57		433	Retrospective cohort	HCV	38	Mortality	MELD score: 12.4 ± 5.7 vs 11.6 ± 5.1 (P = 0.04)	HOMA2-IR2: 8.3 ± 4.9
										HCC
Elkrief et al[7]	2014	342	France	59		236	Retrospective cohort	HCV	24	Mortality	Median MELD score of 10	Not described
Veldt et al[13]	2008	541	Netherlands	50		370	Prospective cohort	HCV	48	HCC	Not described	Not described
Yin et al[11]	2019	436	China	55		278	Prospective cohort	Alcoholic, viral, AIH, and others	12	Hepatic encephalopathy	MELD score: 9.1 ± 2.1 vs 9.2 ± 1.9 (P = 0.537)	Not described
Labenz et al[21]	2020	240	German	60		137	Prospective cohort	Alcohol, viral hepatitis, NAFLD, autoimmune, and cryptogenic	17	Hepatic encephalopathy	MELD score: 10 (8, 15) vs 9 (7, 13) (P = 0.043); Child-Pugh B/C: 42.3% vs 36.9% (P = 0.453)	HbA1c (%) of 5.1 (4.6, 5.5)
Torisu et al[16]	2007	47	Japan	54		47	Retrospective cohort	Alcoholic	81.6	HCC	Not described	Not described
Braia et al[18]	2016	2556	Romania	Not mentioned			Prospective cohort	Not described	48	HCC	Not described	Not described

HBV: Hepatitis B virus; HCV: Hepatitis C virus; PBC: Primary biliary cirrhosis; MELD: Model for End Stage Liver Disease; HCC: Hepatocellular carcinoma; NAFLD: Non-alcoholic fatty liver disease; SBP: Spontaneous bacterial peritonitis; NASH: Nonalcoholic steatohepatitis; AIH: Autoimmune hepatitis; T2DM: Type 2 diabetes mellitus.

Table 2 Newcastle-Ottawa Scale score

Ref.	Year	Type of study	Selection	Comparability	Outcome	Score
Bianchi et al[14]	1994	Retrospective cohort	4	1	3	8
Quintana et al[5]	2011	Prospective cohort	4	2	2	8
Ahn et al[4]	2020	Retrospective cohort	4	0	2	6
Wlazlo et al[6]	2013	Retrospective cohort	3	0	3	6
Holstein et al[10]	2002	Prospective cohort	4	2	2	8
Elkrief et al[7]	2014	Retrospective cohort	3	0	3	6
Liu et al[8]	2016	Retrospective cohort	3	0	3	6
Veldt et al[13]	2008	Prospective cohort	3	0	3	6
Yin et al[11]	2019	Prospective cohort	3	1	3	7
Wang et al[12]	2020	Retrospective cohort	3	1	2	6
Nishida et al[15]	2006	Prospective cohort	4	2	2	8
Ioannou et al[19]	2006	Retrospective cohort	3	2	3	8
N’kontchou et al[20]	2006	Retrospective cohort	3	0	3	6
Labenz et al[21]	2020	Prospective cohort	3	1	3	7
Torisu et al[16]	2007	Retrospective cohort	3	0	3	6
Braia et al[18]	2016	Prospective cohort	4	0	2	6
Yang et al[17]	2007	Retrospective cohort	4	0	3	7