Effect of pentoxifylline on histological activity and fibrosis of nonalcoholic steatohepatitis patients: A one year randomized control trial

Abstract

Background and Objectives: To observe the effect of Pentoxifylline for 1 year on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis (NASH). Materials and Methods: A single center, open label Randomized Control Trial. Patients were included if they had ultrasonographic evidence of fatty liver and nonalcoholic fatty liver disease activity score (NAS) ≥ 5 on liver histology. A total of 35 patients were selected; 25 of PL (Experimental) group and 10 of L (Control) group. PL group received 400 mg pentoxifylline thrice daily along with lifestyle modification and there was only lifestyle modification for the L group. After one year, NAS and fibrosis was compared in both groups. Results: In PL group, NAS improved 2.10 ± 1.07; whereas in L group, NAS was 0.90 ± 0.99 (P = 0.006). As per the protocol analysis, NAS ≥ 2 improved in 15/20 (75%) in PL group and in 3/10 (30%) in L group (P = 0.018). In PL group, the individual component of NAS, steatosis improved from 2.30 ± 0.66 to 0.95 ± 0.76 (P = 0.000), lobular inflammation from 1.65 ± 0.59 to 1.05 ± 0.51 (P = 0.002) and hepatocyte ballooning from 1.50 ± 0.51 to 1.30 ± 0.57 (P = 0.258). In L group, steatosis improved from 2.30 ± 0.68 to 1.40 ± 1.08 (P = 0.01), lobular inflammation and hepatocyte ballooning did not improve. The fibrosis score did not improve in any group. In PL group, NAS improved significantly (P = 0.027; OR=22.76, CI=1.43-362.40) independent of weight reduction. Conclusion: Pentoxifylline for 1 year improves the hepatic histological activity but not fibrosis of NASH patients.

Fibrosis progression rate in a systematic review of placebo‐treated nonalcoholic steatohepatitis

“…The 35 trials included spanned the spectrum of those reported in NASH (Table 1). 18‐52 The median trial duration was 48 weeks, ranging from 24 to 96 weeks. The majority of these trials were small: 10 trials containing ≤20 placebo‐treated participants and 15 trials containing between 21 and 50 placebo‐treated participants.…”

Effect of weight reduction on histological activity and fibrosis of lean nonalcoholic steatohepatitis patient

“…[22] Various modalities of treatment are being tested for the management of NASH. [22] Among different drugs tested, [23] vitamin E, [24,25] pioglitazone, [25] liraglutide, [26] telmisartan, [27] pentoxifylline [28] were found to improve histological activity and fibrosis in different degrees. But these must be balanced with their potential adverse effects.…”

A structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH)

“…Two RCTs (n = 60 and n = 35) and a narrative review reported that PTX improved histological features of NASH, but showed no significant benefit in improving fibrosis (see Table ) . The first Phase II RCT (n = 35) examined PTX vs PBO, with PTX showing significant improvements in liver histology with minimal side effects, including abdominal pain .…”

“…Two RCTs (n = 60 and n = 35) and a narrative review reported that PTX improved histological features of NASH, but showed no significant benefit in improving fibrosis (see Table ) . The first Phase II RCT (n = 35) examined PTX vs PBO, with PTX showing significant improvements in liver histology with minimal side effects, including abdominal pain . The other Phase II RCT (n = 60) examined PTX vs PIO and while both treatments showed significant improvements in hepatic steatosis, the authors concluded that due to greater improvements in patients with NASH, PIO should be used ahead of PTX …”