Multistep approach for treatment of non-alcoholic fatty liver disease – the impact of diet and pioglitazone

Aims: Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, potentially progressing to steatohepatitis, cirrhosis, and hepatocellular cancer. The metabolic syndrome is present in most cases of NAFLD.

Methods: We included patients with elevation of at least 2 liver enzymes (ALAT or ASAT and g-GT) >1.5x UNL. All had liver biopsy and aminopyrine breath testing at baseline. They were subject to undergo a six months intervention period receiving a calory-reduced diet (aiming at max. 1200 Kcal/d) and lifestyle modification. In addition, if necessary, all had to limit their alcohol consumption to 40g/week. If liver enzymes did not improve, patients received pioglitazone 30mg/d for at least 3 months, thereafter individually adjusted if responding. If they still did not respond, pravastatin 40mg/d either replaced pioglitazone or was added after 6 months.

Results: 447 patients with NAFLD were screened. 267 underwent liver histology and had a full workup for exclusion of other chronic liver diseases. 15/115 (13%) had weight loss >5% and normalisation of liver enzymes due to diet only. 50/100 agreed to be treated with pioglitazone alone and returned for follow-up at 12 and 24 weeks, their median histological degree of steatosis was 60%. 17 and 14 patients now have been followed up for 72 and 100 weeks, respectively. For biochemical results see below.

Median values [UNL]	Baseline	12 Weeks	24 Weeks	p-value
ALAT [<0.60 umol/l]	1.53	0.60	0.75	<0.0001
ASAT [<0.60 umol/l]	1.0	0.59	0.59	<0.0001
AP [<1.74 umol/l]	1.6	1.1	1.16	=0.004
g-GT [<0.65 umol/l]	1.81	0.81	0.82	=0.022
Uric Acid [<340 umol/l]	377	337	307	=0.05
Fasting Glucose [<6.4 mmol/l]	4.9	5.3	4.8	NS
Glucose (OGTT, 2hrs)	7.3	n.a.	5.9	=0.03
Fasting Insulin [ng/ml]	85.5	n.a.	81.5	NS
Insulin [ng/ml], 2hrs post OGTT	703	n.a.	428	=0.0008

No changes until 24 weeks were seen for BMI, cholesterol, triglycerides, bilirubine, BSR, CrP, creatinine, prothrombine time. Total body fat composition decreased from 40.4% to 34.9% (p<0.05). The cum. dose of the aminopyrine breath test increased from 6.2% to 8.5% (p<0.05).

Conclusions: Most patients could not achieve a clinically sufficient weight loss by non-medical treatment only in contrast to pioglitazone.