Improvement Of Hepatic Fibrosis Research Articles

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years.

Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line treatments for chronic hepatitis B (CHB). We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase (ALT) improvement, but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis. To assess the benefits of TDF switching to TAF for 3 years on ALT, aspartate aminotransferase (AST), and hepatic fibrosis improvement in patients with CHB. A single center retrospective study on 53 patients with CHB who were initially treated with TDF, then switched to TAF to determine dynamic patterns of ALT, AST, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE) reading improvement at switching week 144, and the associated factors. The mean age was 55 (28-80); 45.3%, males; 15.1%, clinical cirrhosis; mean baseline ALT, 24.8; AST, 25.7 U/L; APRI, 0.37; and FIB-4, 1.66. After 144 weeks TDF switching to TAF, mean ALT and AST were reduced to 19.7 and 21, respectively. From baseline to switching week 144, the rates of ALT and AST < 35 (male)/25 (female) and < 30 (male)/19 (female) were persistently increased; hepatic fibrosis was also improved by APRI < 0.5, from 79.2% to 96.2%; FIB-4 < 1.45, from 52.8% to 58.5%, respectively; mean APRI was reduced to 0.27; FIB-4, to 1.38; and mean SWE reading, from 7.05 to 6.30 kPa after a mean of 109 weeks switching. The renal function was stable and the frequency of patients with glomerular filtration rate > 60 mL/min was increased from 86.5% at baseline to 88.2% at switching week 144. Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4 scores, as well as SWE reading, the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile. This is a retrospective study of a prospectively collected registry of patients with MASLD and compensated advanced chronic liver disease (cACLD) who underwent EGR. Patients were categorized as (1) monotherapy: EGR alone and (2) combination therapy: GLP-1RA prescribed within 6months prior to or after EGR. Outcomes included changes in noninvasive tests of hepatic fibrosis, weight profile, and insulin resistance status at 12months. Thirty patients (body mass index 40.7 ± 9.3kg/m2) were included. Of these, 12 patients (40%) underwent EGR monotherapy, and 18 patients (60%) underwent EGR + GLP-1RA combination therapy. Combination therapy group experienced greater improvements in fibrosis compared to monotherapy group (alanine aminotransferase: reduction by 55 ± 23% vs 29 ± 22% (p = 0.008), NAFLD fibrosis score: reduction by 181 ± 182% vs 30 ± 83% (p = 0.04), liver stiffness measurement on transient elastography: reduction by 54 ± 12% vs 14 ± 45% (p = 0.05)). There were greater reductions in hemoglobin A1c and homeostatic model assessment for insulin resistance in combination therapy compared to monotherapy (p < 0.05). At 12months, the combination therapy group experienced 18.2 ± 6.6% TWL, while monotherapy group experienced 9.6 ± 3.3% TWL (p = 0.004). In patients with MASLD and cACLD, combination of EGR with GLP-1RA is associated with greater improvements in hepatic fibrosis, weight profile, and insulin resistance compared to EGR alone.

Effect of Transoral Outlet Reduction on Hepatic Fibrosis in Roux-en-Y Gastric Bypass Patients with Weight Regain and Non-alcoholic Fatty Liver Disease.

Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with worsening of liver outcomes. However, the effect of transoral outlet reduction (TORe) on liver fibrosis in RYGB patients with weight regain and possible advanced fibrosis remains unknown. This was a retrospective analysis of prospectively collected data of RYGB patients who underwent TORe for weight regain. Only patients with possible advanced fibrosis were included. TORe was performed using either an endoscopic suturing device (S-TORe) or plication device (P-TORe) to reduce the gastrojejunal anastomosis (GJA) and pouch sizes. Primary outcomes included changes in non-invasive tests (NITs) for fibrosis at 6-12months. Secondary outcomes included weight loss and changes in insulin resistance and lipid profile at 6-12months. Fifty RYGB patients were included. Baseline age and BMI were 55 ± 11years and 40.1 ± 7.3kg/m2. Baseline GJA and pouch sizes were 20 ± 7mm and 5 ± 2cm, respectively. Thirty patients (60%) underwent S-TORe and 20 patients (40%) underwent P-TORe. At 12months following TORe, there were statistically significant improvements in NITs for fibrosis, including ALT, AST and FIB-4. There was a trend towards significant improvement in liver stiffness measurement on transient elastography. Patients experienced 8.8 ± 11.2% total weight loss (TWL) (p < 0.0001), with 60% experiencing at least 10% TWL. Additionally, there was a significant improvement in HbA1c and a trend toward significant improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), suggestive of improved insulin sensitivity. TORe is associated with an improvement in hepatic fibrosis in patients with NAFLD and possible advanced fibrosis.

Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice

Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

S1335 Tenofovir Disoproxil Fumarate Switching to Tenofovir Alafenamide for Three Years Resulted in Improvement of Hepatic Fibrosis by APRI and FIB-4 Score as Well as Shear Wave Elastography in Patients With Chronic Hepatitis B

Introduction: Tenofovir Alafenamide (TAF) is one of the first-line treatments (Rx) for chronic hepatitis B (CHB) with comparable antiviral effects, better safety profile than Tenofovir Disoproxil Fumarate (TDF). We have showed switching from TDF to TAF Rx for 96 weeks resulted in further ALT improvement, but data remain lacking on its long-term effects on hepatic fibrosis. The present study assessed effects of TDF switching to TAF for 3 years (144 weeks) on AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE). Methods: A single center retrospective study on 53 CHB patients initially treated with TDF, then switched to TAF to determine patterns of ALT, AST, APRI, FIB-4 scores, SWE improvement at Rx week (Rx wk) 144, and the associated factors. Results: Mean age 55 (28-80); 7.7%, spleen size >12 cm; 11.3%, platelets < 120 x109/L; mean baseline ALT, 24.8 (7-108); AST, 25.7 (15-89) IU/L; APRI, 0.37 (0.13-0.92); FIB-4, 1.66 (0.49-5.33). After switching, means of ALT, AST, APRI, and FIB-4 were all improved persistently. Mean ALT was reduced to 20.8 (8-106), 19.1 (7-40), 19.5 (9-42), 19.7 (8-42) (Fig. 1A); mean AST, 21.4 (13-59), 20.3 (14-38), 21.2 (13-41), 21 (13-39) (Fig. 1B); mean APRI, 0.29 (0.09-0.78), 0.28 (0.12-0.69), 0.28 (0.13-0.64), 0.27 (0.11-0.51) (Fig. 1C); mean FIB-4, 1.43 (0.39-3.94), 1.46 (0.49-3.68), 1.43 (0.50-3.33), 1.38 (0.39-2.76) (Fig. 1D); at Rx wk 24, 48, 96, 144, respectively. Mean SWE reading was improved from 7.05 to 6.30 kilopascal (kPa), improvement rate to fibrosis stage 0-1 was increased from 32/50 (64%) to 43/50 (86%) after a mean of 108 wks switching (4-240). Univariate analysis showed pre-Rx spleen >12 cm (p=0.031); platelet < 120 x109/L (p=0.018), APRI < 0.5 (p=0.047), but not FIB-4 < 1.45 (p=0.055), ALT < 40 (p=0.460), AST < 40 (p=0.460) at Rx wk 24 were associated with SWE improvement. Multivariate analysis showed hepatic fibrosis improvement by SWE was negatively associated with pre-Rx spleen >12 cm (p=0.016), independently to platelet < 120 x109/L (p=0.250), APRI < 0.5 (p=0.448), and FIB-4 < 1.45 (p=0.244) at Rx wk 24. Conclusion: Our data confirmed switching from TDF to TAF for 3 years results in not only persistent ALT, AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4, as well as by SWE reading. SWE improvement was significantly negatively associated with pre-Rx spleen >12 cm, independent to platelet < 120 x109/L, APRI < 0.5, and FIB-4 < 1.45 at Rx wk 24.Figure 1.: Dynamic changes in mean reduction of ALT, AST, APRI, and FIB-4 scores from baseline to treatment week 144 after TDF switching to TAF

Further Insights Into the Impact of Bariatric Surgery on the Progression of Nonalcoholic Fatty Liver Disease

Seeberg KA, Borgeraas H, Hofsø H, et al. Gastric bypass versus sleeve gastrectomy in type 2 diabetes: effects on hepatic steatosis and fibrosis: a randomized controlled trial. Ann Intern Med 2022;175:74–83. Bariatric surgery has an increasingly recognized role in treating metabolic syndrome, and benefits nonalcoholic fatty liver disease (NAFLD) specifically (Gastroenterology 2020;159:1290–1301). However, the extent to which bariatric surgery might impact NAFLD progression and whether various bariatric approaches affect this differently remain relatively unexplored. Seeberg et al undertook a single-center randomized trial in which 100 participants with type 2 diabetes mellitus (T2DM) and obesity were randomized 1:1 to either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and followed up to 1 year postoperatively. Although the primary trial outcomes related to T2DM remission have been published (Lancet Diabetes Endocrinol 2019;7:912–924), this present study described predefined outcomes related to hepatic steatosis (assessed via liver fat fraction on magnetic resonance imaging), enhanced liver fibrosis test (as a proxy of hepatic fibrosis), and other noninvasive NAFLD markers. At 1-year follow-up, there was a 20% reduction (95% CI, 23% to 17%) in liver fat fraction in the SG group and 22% (95% CI, 24% to 19%) observed in the RYGB group, with no significant difference between groups. Almost all patients—94% of the SG group and 100% of the RYGB group—had no or low-grade steatosis at 1 year (compared with ∼25% of participants at baseline). The enhanced liver fibrosis score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. Weight loss, improvements in lipid profile, and remission rates for T2DM favored RYGB compared with SG. Collectively, these data demonstrate that both evaluated forms of bariatric surgery are of comparable high efficacy in improving hepatic steatosis, although this may not translate into short-term improvements in hepatic fibrosis. Study limitations include it being a single-center trial, possible underpowering for NAFLD-related outcomes (given the primary outcome relating to T2DM), and the reliance on a noninvasive marker (enhanced liver fibrosis) as the main measure of hepatic fibrosis, with no liver biopsies obtained. Given that steatohepatitis typically progresses to fibrosis over the course of years rather than months in NAFLD, results of the already planned longer-term follow-up will be of great pertinence for gauging the full impact of bariatric surgery. Splitting Hairs: Folliculin Parts the Good From the Bad in mTORC1 Control Over Lipid MetabolismGastroenterologyVol. 163Issue 2PreviewGosis BS, Wada S, Thorsheim C, et al. Inhibition of nonalcoholic fatty liver disease in mice by selective inhibition of mTORC1. Science 2022;376(6590):eabf8271. Full-Text PDF

1333-P: Therapeutic Potential of DA-1726, a Novel Oxyntomodulin Analogue, in a Diet-Induced NASH Mouse Model

DA-1726 is a novel balanced long-acting GLP-1/glucagon receptor dual agonist, which is under preclinical development for the treatment of obesity. DA-1726 represented a superior efficacy to semaglutide (SEMA) in weight loss in various animal studies. In this study, we evaluated the therapeutic potential of DA-1726 for the treatment of nonalcoholic steatohepatitis (NASH) . To induce NASH, male mice were given a diet containing 40% total fat, 20% fructose, and 2% cholesterol for 30-week. After then DA-1726 and SEMA were subcutaneously injected every three days for 8-week. At the end of treatment, vehicle control, DA-1726 (100 or 200 nmol/kg) and SEMA (250 nmol/kg) significantly reduced body weight compared to baseline (+10.4%, -8.9%, -17.2%, and -12.9%, respectively) . Plasma clinical chemistry parameters (ALT, AST, ALP and T-BIL) and hepatic fat accumulation were significantly decreased by DA-1726. The reduction of plasma glucose and total cholesterol induced by DA-1726 200 nmol/kg was superior to that of SEMA. In a histopathological analysis of steatosis, lobular inflammation, and ballooning in the liver, DA-1726 showed an excellent improvement in NAFLD Activity Score compared to SEMA (NAS: 6.75 for vehicle control, 3.88 and 3.63 for DA-1726, and 5.00 for SEMA) . Liver fibrosis was assessed by Masson Trichrome stain. Improvement of hepatic fibrosis by DA-1726 was also observed (fibrosis score: 1.88 for vehicle control, 1.25 and 1.13 for DA-1726, and 1.50 for SEMA) . In the liver tissue, the expression of inflammatory (Tnfa, Il-1β, and Ccl2) and fibrotic (Acta2, Timp1, Col1a1, Col3a1, and Mmp9) genes were significantly decreased by DA-1726 treatment. In particular, the DA-1726 low-dose group showed a higher efficacy despite lower weight loss compared to SEMA. This is thought to be a result of the dual actions of DA-1726 to GLP-1 and glucagon receptors. Taken together, our findings suggest that DA-1726 has a therapeutic potential for NASH in addition to obesity and type 2 diabetes. Disclosure I.Jung: None. T.Kim: None. M.Goo: None. M.Kim: None. Y.Chae: None.

Improvement in hepatic fibrosis estimated by Fibrosis-4 index in pegloticase treated chronic refractory gout patients.

To determine whether lowering serum urate (SU) affects the course of non-alcoholic fatty liver disease (NAFLD). Retrospective data analysis from chronic refractory gout patients who participated in two 6-month pegloticase randomised clinical trials compared patients who received pegloticase biweekly to those who received placebo. Patients with persistent urate-lowering to <1 mg/dL in response to biweekly pegloticase (responders, n=36) were compared to those who received placebo (n=43). NAFLD was assessed using the Fibrosis-4 (Fib-4) index. Comparisons between groups were carried out using 2 sample Wilcoxon tests or regression analysis. At baseline the mean (standard deviation [SD]) Fib-4 values were 1.40 (0.86) in pegloticase responders, and 1.04 (0.53) in patients receiving placebo. Patients receiving placebo exhibited a change of 0.26 (0.41) in Fib-4 score over 6 months vs 0.13 (0.62) for pegloticase responders (p=0.048). When only patients with a Fib-4 value >1.3 were considered (n=27), a significant difference in the change in the Fib-4 values between pegloticase responders vs. placebo was observed (-0.15 [0.67] vs. 0.7 [0.42], p=0.04). The correlation between the SU area under the curve (AUC) over the 6-month trial period and the change in Fib-4 value was R=0.33 (p=0.0004). Multivariable analysis indicated SU AUC was the only significant contributor to the change in Fib-4 values (p=0.018). Persistent lowering of SU significantly reduced Fib-4 scores, implying a possible effect on NAFLD progression. These results support the consideration of a complete analysis of the impact of profound urate-lowering on NAFLD as measured by the Fib-4 index.

S1190 Hepatic Fibrosis Improvement Does Not Differ Between Type of Antiviral Therapy in Chronic Hepatitis B Patients

Introduction: Chronic Hepatitis B infection (HBV) is the most common viral hepatitis infection worldwide. HBV can result in progressive liver injury culminating in significant inflammation and fibrosis. The aim of this study is to assess the effectiveness of various antiviral therapies on hepatic fibrosis in chronic HBV infection using noninvasive markers in a community setting. Methods: A retrospective study was conducted in chronic HBV patients seen at the Liver Associates of Texas Hepatology clinics in Houston, Texas, seen from 1/2018 to 5/2021. Epidemiological and clinical data of HBV patients treated with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide were analyzed. APRI and FIB-4 scores, which are noninvasive markers of fibrosis, were calculated for all patients at baseline (before treatments) and 6 months post sustained virologic response (SVR). A repeated measures ANOVA analysis was used to assess fibrosis trends between the three treatments and within a single treatment group. Results: A total of 123 patients were reviewed. 64.2% of patients were male, with the mean age of 54.0 years. The ethnic breakdown was: 56.9% Asian, 24.4% African-American, 8.1% White, 4.9% Hispanic, 0.8% Native Hawaiian/Pacific Islander, and 4.9% Unknown. 85 patients received treatment, with 20 patients receiving entecavir, 29 tenofovir alafenamide, and 36 tenofovir disoproxil fumarate. Both APRI and FIB-4 scores showed a statistically significant difference from before treatment to 6 months post treatment independent of treatment type(APRI: p= 0.035; FIB-4: p= 0.037). Post-hoc analysis showed a statistical significant decrease from baseline to 5 months post initiation of treatment for both APRI (Mean difference = 0.229, pbonferroni = 0.035) and FIB4 (mean difference = 0.168, pbonferroni = 0.037). There was no statistical significant interactions between treatment type and FIB4 or APRI scores. Conclusion: This study demonstrated that in patients with Hepatitis B, there was a statistically significant improvement in hepatic fibrosis within 6 months of antiviral therapy initiation and that there is no significant difference in using any of the three types of antiviral treatments: entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide in this population of HBV patients.Figure 1.: Title: APRI scores over time in patients treated with Entecavir, Viread, and Vemlidy. Legend: Blue = entecavir. Gray = tenofovir alafenamide, Yellow = tenofovir disoproxil fumarate.Table 1.: GIST characteristics of patients with both abscess and GIST.

Nonalcoholic fatty liver disease: another leap forward.

In 2020, there have been substantial advances in nonalcoholic fatty liver disease mechanisms, diagnostics and treatment. Key developments include the identification of a cellular and tissue signature to provide new insights into pathophysiology, advancements in non-invasive diagnostics and publication of interim results of the first phase III trial to demonstrate improvement in hepatic fibrosis.

Effect of Successful Direct Acting Antivirals Therapy on Liver Stiffness in Patients with Chronic HCV Infection

Background: Achievement of sustained virological response [SVR] and improvement of hepatic fibrosis are the essential goals for therapy of chronic hepatitis C [CHC] with direct acting antivirals [DAAs] therapy. Early detection and management of hepatic fibrosis can significantly improve the prognosis of CHC in clinical practice. Aim of the work: To assess the effect of successful DAAs therapy on liver stiffness in patients with CHC. Methods: This study included 100 patients with chronic HCV-related liver disease. All were treated with Sofosbuvir-based regimen for 12 weeks on outpatient base. HCV treatment applied according to the protocol designed by the Egyptian National Committee for Control of Viral Hepatitis. Follow up continued for 12 weeks [after the end of treatment [EOT]] to estimate effect of successful DAAS therapy on liver stiffness using Shear Wave Elastography [SWE], aminotransferase-to platelet ratio index [APRI] and Fib-4 score before initiation of antiviral therapy, at end of treatment [EOT] and 12 weeks after EOT [SVR12]. Results: Platelets significantly increased, ALT and AST decreased and mean values of APRI, Fib-4 score and Liver stiffness assessment were significantly reduced in all patients at SVR12. Hemoglobin levels significantly reduced in patients receiving ribavirin 12 weeks after EOT. Conclusions: Elimination of HCV after successful DAAS treatment was associated with a significant improvement of the liver stiffness at both EOT and 12 weeks afterwards EOT as evidenced by SWE, Fib-4 score and APRI index

RhizomaParidis saponins ameliorates hepatic fibrosis in rats by downregulating expression of angiogenesis‑associated growth factors.

Previously, we demonstrated that Rhizoma Paridis saponins (RPS), the major active component of Rhizoma Paridis, may exhibit hepatoprotective effects. The present study aimed to identify the potential mechanism of RPS on hepatic injury and improvement in hepatic fibrosis (HF). A HF model was created in Sprague-Dawley rats by administration of carbon tetrachloride. RPS was administered for treatment following creation of the HF model. The protein and mRNA expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), extracellular signal-regulated kinase (ERK)1/2 and α-smooth muscle actin (SMA) was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. RPS was demonstrated to improve hepatic inflammation and decrease HF severity according to hematoxylin and eosin and Masson trichrome staining. Following RPS treatment, the level of alanine aminotransferase, aspartate aminotransferase and malondialdehyde, and expression levels of the mRNA and protein of VEGF, ERK1/2, PDGF and α-SMA in the model group was decreased. By contrast, the content of glutathione-PX and superoxide dismutase was increased. These data suggest that RPS may treat HF primarily through downregulation of the expression levels of the mRNA and phosphorylated VEGF, ERK1/2, PDGF and α-SMA proteins.

Study the Effect of Weight Loss in Improvement of Hepatic Fibrosis in Patients with Chronic HCV

Study the Effect of Weight Loss in Improvement of Hepatic Fibrosis in Patients with Chronic HCV

EFFICIENCY OF DAA ON HCV-INFECTED KIDNEY TRANSPLANT PATIENTS AT CHO RAY HOSPITAL – VIETNAM

Purposes:To evaluate the efficiency of DAA (Direct Antiviral Agent), in particular sofosbuvir, ledipasvir in Hepatitis C treatment for patients with kidney transplants. Take note in the side effects and drug interactions during the treatment processes. Method:Intervention, prospective, cohort, case studies, non-randomized, open on to all kidney transplant cases with chronic Hepatitis C tested positive HCV RNA (+); the patients from the cases above had agreed to be the research’s subjects from 11/2015 to 8/2018 at Cho Ray hospital. Two regimens Sofosbuvir/Ribavirin and Sofosbuvir/Ledipasvir have been used for treatments, which depend on HCV genotype and liver cirrhosis levels. Results:In 440 patients who had been observed after kidney transplants, 44 cases anti HCV (+), 29 cases HCV RNA(+) and 4 cases HBV/HCV Confection. There were 15 cases with chronic Hepatitis C participated in study. Males made up 66.6% of the group with the average age 49± 7.06 yrs. There were 6.7% of them not taking full-course treatments. 80% of the patients were infected with only C virus, while 20% of the patients were co-infected with B and C virus. 40% of them had histories of previous blood transfusions. The ratio of patients with elevated liver enzymes was 33.3%. Genotype 1 (a and b) was 33.3%, genotype 2 was 6.7%, genotype 6 was 53.3% and 6.7% unidentifiable genotype. There were 2 cases which were treated with Sofosbuvir/Ribavirin regimen and 13 cases which were treated with Sofosbuvir/Ledipasvir regimen. Rapid virologic response (RVR) is 100%. Sustained virologic response (SVR) within 12 weeks and 24 weeks is 100%. Relapse ratio 0%. In regimen using Sofosbuvir / Ledipasvir, the side effects are mild and transient, including skin irritation, digestive disorders which account for 7.7%. In regimen using Sofosbuvir / Ribavirin, side effects including severe anemia, fatigue, loss of appetite related to Ribavirin occur in 50% of cases (1/2) which lead to stopping treatment termination after 10 weeks and being replaced with treatment regimens using sofosbuvir / daclatasvir with good results. No major interactions are recorded when being used simultaneously with immunosuppressive drugs such as Prograf, Sandimmum Neoral, Mycophenolate Mofetil, Prednisone in this research. No renal failure occurs. Liver enzymes are improved during and after treatment. There is improvement scale of fibroscan after treatment. Conclusion: Sofosbuvir/ Ledipasvir regimen have proven their effectiveness in treating chronic Hepatitis C genotype 1, 2 and 6 on kidney-transplanted patient, with RVR at 100%, SRV 12 and SRV 24 at 100%. Sofosbuvir/ ribavirin regimen have proven to be effective in eliminating virus and be economical in treating chronic hepatitis C genotype 2, however, the anemia side effect of ribavirin need to be considered in case it become serious and now the first-line regimens are Sofosbuvir/daclatasvir or sofosbuvir/ Velpatasvir. There is improvement of hepatic fibrosis after treatment DAA.

The Role of Vitamin E in the Treatment of NAFLD.

There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect.

The Role of Cannabinoids in the Setting of Cirrhosis.

Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

364 - Increased Angiotensin II/Angiotensin-(1-7) Levels in Chronic Hepatitis C Patients Who had Sustained Virologic Response with Direct-Acting Antiviral Drugs Suggest their Role in the Improvement of Hepatic Fibrosis

364 - Increased Angiotensin II/Angiotensin-(1-7) Levels in Chronic Hepatitis C Patients Who had Sustained Virologic Response with Direct-Acting Antiviral Drugs Suggest their Role in the Improvement of Hepatic Fibrosis

Long-Term Follow-Up Study of Liver-Related Outcome After Bilio-Pancreatic Diversion in Patients with Initial, Significant Liver Damage.

Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis. To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage. This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score. During a median follow-up of 78months, median weight decreased from 119 to 78kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0kg/m2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from -0.929 (-1.543 to -0.561) to -1.609 (-2.056 to -1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%). Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion.

FRI-381 - Sustained and continued improvement in hepatic fibrosis beyond the first year following hepatitis C virus treatment

FRI-381 - Sustained and continued improvement in hepatic fibrosis beyond the first year following hepatitis C virus treatment

PS-092 - Improvement of hepatic fibrosis in patients with non-alcoholic steatohepatitis treated with selonsertib is associated with improvement of patient-reported outcomes (PROS)

PS-092 - Improvement of hepatic fibrosis in patients with non-alcoholic steatohepatitis treated with selonsertib is associated with improvement of patient-reported outcomes (PROS)