Combined PEG3350 Plus Lactulose Results in Early Resolution of Hepatic Encephalopathy and Improved 28-Day Survival in Acute-on-Chronic Liver Failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality in those with hepatic encephalopathy (HE). Polyethylene glycol (PEG) 3350 electrolyte solution can ensure rapid gut catharsis, which may resolve HE more effectively than lactulose. In this open-label-randomized trial, we compared PEG+lactulose versus lactulose alone in ACLF with HE grade ≥2 for efficacy and outcome. PATIENTS AND METHODS: Patients were randomized to receive PEG (2 L q12 h) followed by lactulose (30 mL q8 h) or standard medical treatment [SMT, lactulose (titrated 30 mL q8 h)]. Endpoints were HE grade improvement at 24 hours, 48 hours, and 7 days using hepatic encephalopathy scoring algorithm (HESA), ammonia reduction, HE resolution, and survival benefit. RESULTS: Of 60 patients, 29 were randomized to PEG+lactulose arm and 31 to SMT. In the PEG arm, early reduction in HESA score was noted in more persons [18 (62.1%) vs. 10 (32.2%); P=0.021] with a shorter median time to HE resolution [4.5 (3 to 9) d vs. 9 (8 to 11) d; P=0.023]. On multivariate analysis, age [hazard ratio (HR),1.06 (1.00 to 1.13); P=0.03], HESA score [HR, 6.01 (1.27 to 28.5); P=0.024], and model for end-stage liver disease [HR, 1.26 (1.01 to 1.53); P=0.022] were predictors of mortality at 28 days. Ammonia level or reduction did not correlate with HE grades. Adverse events included excessive diarrhea (20.6% vs. 9.6%) in the PEG and SMT arms, albeit without dyselectrolytemia or worsened renal function. In the PEG versus SMT arm, survival at 28 days were 93.1% versus 67.7% (P=0.010) and at 90 days was 68.9% versus 48.3% (P=0.940), respectively, with fewer persons relapsing with HE in the PEG arm. CONCLUSIONS: PEG resulted in early and sustained HE resolution with improved short-term survival making, it a suitable and safe drug in patients with acute HE in ACLF.

Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C.

BACKGROUND AND AIM: Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our "real life" experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. METHODS: A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. RESULTS: Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. CONCLUSIONS: Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

Functional reconstitution of defective myeloid dendritic cells in chronic hepatitis C infection on successful antiviral treatment.

OBJECTIVE: Poor cellular trafficking and suboptimal T-cell responses in liver, the hall marks of chronic hepatitis C virus (CHC) infection, might be attributed to defective antigen presentation. Controversy exists regarding role of myeloid dendritic cells (DCs) in CHC and response to antiviral treatment. This study examines functional status of DCs before and after completion of treatment with the aim to find any modulatory effect. DESIGN: Frequency and functions of monocyte-derived DCs (mo-DCs) were evaluated in CHC (n = 25), before the start of therapy (CHC(0) ). These patients were then put on treatment with peg-interferon-α plus ribavirin for 24 or 48 weeks, and the mo-DC functions were evaluated after 6 months of completion of treatment (CHC(6) ) again, using multicolour flow cytometry, endocytosis assay, cytokine assay and mixed lymphocyte reaction. RESULTS: Pre-treatment frequency of mo-DCs in CHC(0) was lower than that in healthy controls, which became close to normal in patients who achieved virological response (SVR+, n = 20) but not in non-responders (SVR-, n = 5). Pre-treatment levels of CD83, CD80 and CD86 on mo-DC in SVR(0) +, but not SVR(0) -, got upregulated after lipopolysaccharide stimulation supporting the hypothesis that DCs play deciding role in response to therapy. Post-treatment allostimulatory and phagocytosing capacity of mo-DCs in SVR+ patients indicated regain in functional capacity in these patients but not in SVR- patients. CONCLUSIONS: Our results indicate that DCs in CHC patients exhibiting mature and functional phenotype prior to therapy achieve sustained virological response suggesting that functional modulation of defective DCs is directly associated with successful response to therapy.

Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin treatment in a patient with chronic hepatitis C.

Hepatitis C virus (HCV) infection has been associated with several cutaneous diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon alfa (PEG-INF) combined with rivabirin also leads to many skin side effects including injection site reaction, generalized skin rashes, pruritus, dry skin, alopecia, and exacerbation of autoimmune processes, particularly psoriasis, lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933-939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV in chronic hepatitis C both in dark-skined as well as Caucasian. We report the first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin administration in a non-Caucasian patient with genotype 4.

Treatment of chronic hepatitis C in end stage renal disease: experience at a tertiary care centre.

INTRODUCTION: Treatment of patients with chronic hepatitis C (CHC) is difficult in the setting of end stage renal disease (ESRD). The present study aimed to analyze the treatment outcome in patients with CHC and ESRD, being evaluated for kidney transplantation. METHODS: Data of 65 patients of ESRD with CHC (males: 53, mean age: 39.2 +/- 14.4 years) was analysed retrospectively. Patients were treated with either pegylated or conventional interferon (IFN) without ribavirin. Treatment response was assessed for rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR) and sustained virological response (SVR). RESULTS: All patients were receiving hemodialysis (duration 1-60 months). Sixteen patients (25%) (genotype 1: 11, genotype 3: 4, genotype 2: 1) agreed for treatment (13 pegylated IFN and 3 conventional IFN). RVR was achieved in 7 patients (44%) and out of 11 patients (69%) who achieved EVR, ETR was achieved in 7 (44%) patients. Seven patients (44%) dropped out during treatment (2 because of side effects). SVR could be demonstrated in one of 7 patients who achieved ETR (6 patients were lost to follow up after ETR). CONCLUSIONS: In our experience, dropouts before, during and after treatment are a major problem in patients with CHC and ESRD. Of those who complete treatment, around half of them are able to achieve the end of treatment response.

Association between nonalcoholic fatty liver disease and inflammatory periodontal disease: A case­control study.

BACKGROUND: Recent evidence suggests an interconnection between chronic periodontal disease and systemic diseases. AIM: The aim of this study is to evaluate the possible association between nonalcoholic fatty liver disease (NAFLD) and inflammatory periodontal disease among north Indian population. SETTINGS AND DESIGN: Tertiary health care center, cross-sectional case-control observational study. MATERIALS AND METHODS: A total of 40 cases, i.e., patients with NAFLD and 40 healthy volunteers were included over a period of 8 months and their periodontal status was compared. The status of their hepatic health was ascertained by anthropometric, imaging, and biochemical evaluation including ultrasound examination of abdomen and transient elastography. STATISTICAL DATA ANALYSIS: Paired t-test, multivariate logistic regression analysis using IBM SPSS STATISTICS (version 22.0, Armonk, NY: IBM Corp). RESULTS: The study revealed that only 11.9% and 20% of participants had periodontitis, in healthy controls and hepatic disease patients, respectively. A statistically significant difference was observed in clinical parameters of periodontal status, except for malocclusion. Comparative analysis of tumor necrosis factor-α (TNF-α), interleukin-6, C-reactive protein, and cytokeratin-18 revealed differences in mean scores, though statistically nonsignificant. Only aspartate transaminase, number of missing teeth, and bleeding on probing (BOP) were observed with higher odds ratios for hepatic disease patients. Spearman correlation analysis revealed significant positive correlations between TNF-α and BOP, for cases. CONCLUSION: Patients with hepatic disease showed a higher prevalence of periodontal disease, worse oral hygiene and periodontal health status compared to healthy individuals.