Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis.

Oral and topical zinc have been used for the treatment of acne, but there is a lack of definitive evidence for their efficacy. (a) To determine if mean serum zinc levels differ between acne patients and controls and (b) to determine the efficacy of zinc preparations in the treatment of acne. A systematic review and meta-analysis was performed according to recommended PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] guidelines. Subjects with acne had significantly lower serum zinc levels compared to controls. Patients who were treated with zinc had a significant improvement in mean inflammatory papule count compared to those who were not treated with zinc. There was no significant difference in the incidence of side effects in zinc supplementation vs comparators. Acne patients have decreased serum zinc levels. Zinc is effective for the treatment of acne, particularly at decreasing the number of inflammatory papules, when used as monotherapy or as an adjunctive treatment.

Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.

BACKGROUND: High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1. METHODS: We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I(2) statistic ≥50%. RESULTS: Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728). CONCLUSIONS: SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.

Tolerability and effectiveness of sofosbuvir and simeprevir in the post-transplant setting: systematic review and meta-analysis.

BACKGROUND: Outcome data on simeprevir and sofosbuvir (SMV+SOF) in patients with liver transplantation (LT) with hepatitis C virus genotype 1 (HCV-1) are limited with individual studies having a small sample size and limited SVR12 (sustained virological response) data. Our goal was to perform a meta-analysis to study the outcome of SMV+SOF±ribavirin (RBV) in recipients with LT. METHODS: In April 2015, we conducted a literature search for 'simeprevir' in MEDLINE/EMBASE and five major liver meetings. We included studies with SVR12 data in ≥5 post-LT mono-infected HCV-1 patients treated with SMV+SOF±RBV. We used random-effects models to estimate effect sizes, and the Cochrane Q-test (p value <0.10) with I(2) (>50%) to assess study heterogeneity. RESULTS: We included nine studies with a total of 325 patients with post-LT. Studies included mostly men (59-81%). Pooled SVR12 was 88.0% (95% CI 83.4% to 91.5%). In two studies, HCV-1a patients with mild fibrosis (n=108) had an SVR12 rate of 95.0% (95% CI 82.4% to 98.7%), which was significantly higher than that of HCV-1a patients with advanced fibrosis (n=49) with an SVR12 rate of 81.7% (95% CI 69.8% to 89.5%), OR 4.2 (95% CI 1.1 to 16.1, p=0.03). The most common pooled side effects were: fatigue 21% (n=48/237), headache 9% (n=23/254), dermatological symptoms 15% (n=38/254), and gastrointestinal symptoms 6% (12/193). CONCLUSIONS: SMV+SOF±RBV is safe and effective in recipients with LT with HCV-1 infection.

Re-treatment of patients with chronic hepatitis C virus genotype 4 infection with pegylated interferon and ribavirin: a meta-analysis.

BACKGROUND: An estimated 170 million people worldwide are infected with hepatitis C virus (HCV). HCV genotype 4 (HCV-4)-the most prevalent hepatitis C strain in the Middle East and Africa-is difficult to treat, with an estimated sustained virological response (SVR) of 53% when using pegylated interferon and ribavirin (P/R) in treatment-naïve patients with HCV-4 infection. In regions where access to direct-acting antivirals is limited, re-treatment of patients who failed therapy with another course of P/R may be an option if the success rate is acceptable. OBJECTIVES: We aimed to determine the SVR from retreatment with P/R in treatment-experienced patients with HCV-4 infection. METHODS: We performed a meta-analysis using MEDLINE and EMBASE searches, and by reviewing article bibliographies and abstracts from recent Liver Society Meetings. Original studies featuring at least 10 adult, treatment-experienced patients with HCV-4 infection failing prior interferon-based therapy and receiving subsequent re-treatment with P/R were included. RESULTS: 3 studies were included. Overall pooled SVR was 32.7%, or 41/126 patients. No significant heterogeneity existed among the studies. One study reported higher SVR of 50% in previous relapsers, compared with 23% in previous non-responders. CONCLUSIONS: As expected, treatment-experienced patients achieved lower rate of SVR compared with previously reported SVR for treatment-naïve patients with HCV-4 infection. The abysmal rate of success from re-treatment with P/R supports the use of direct-acting antivirals whenever re-treatment is considered, even in resource-limited regions.

Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis.

BACKGROUND: Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs. We performed a meta-analysis of SVR predictors in HCV-4 versus HCV-1, 2, and 3 patients treated with PEG-IFN+RBV. METHODS: In November 2013, we searched for 'genotype 4' in MEDLINE/EMBASE databases and scientific conferences. We included original articles with ≥25 treatment-naïve HCV-4 and comparisons to HCV-1, 2, and/or 3 patients treated with PEG-IFN+RBV. Random effects modelling was used with heterogeneity defined by Cochrane Q-test (p value<0.10) and I(2) statistic (>50%). RESULTS: Five studies with 20 014 patients (899 HCV-4; 12 033 HCV-1; and 7082 HCV-2/3 patients) were included. SVR was 53% (CI 43% to 62%) for HCV-4, 44% (CI 40% to 47%) for HCV-1; and 73% (CI 58% to 84%) for HCV-2/3. SVR with EVR (early virological response) was 75% (CI 61% to 86%) in HCV-4; 64% (CI 46% to 79%) in HCV-1; and 85% (CI 71% to 93%) in HCV-2/3. SVR without EVR was 10% (CI 6% to 17%) for HCV-4; 13% (CI 12% to 15%) for HCV-1; and 23% (CI 16% to 33%) for HCV-2/3. CONCLUSIONS: SVR rates are similar in HCV-4 (∼50%) and HCV-1 (∼40%). Lack of EVR is a good stopping rule for HCV-4 and HCV-1 since only 10% subsequently achieve SVR. In HCV-4 patients with EVR, three-quarters can expect to achieve SVR with PEG-IFN+RBV.

Treatment of Acute Hepatitis C Infection with Pegylated Interferon and Ribavirin in Patients Coinfected with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Of the 35 million human immunodeficiency virus (HIV)-positive patients worldwide, 10-40% are coinfected with chronic hepatitis C virus (HCV). Compared to HCV-monoinfected patients, those coinfected experience decreased spontaneous HCV clearance, accelerated liver fibrosis, and a decreased response to anti-HCV therapy. We conducted a meta-analysis to estimate the efficacy of treating acute HCV in HIV-positive patients with peginterferon and ribavirin combination therapy. METHODS: Two authors independently searched MEDLINE and EMBASE (2014) for English articles, and reviewed bibliographies and abstracts from major liver and HIV conferences (2011-2013). Original studies featuring at least 10 treatment-naive, HIV-positive adults infected with acute HCV and treated with peginterferon and ribavirin were included. Analyses were calculated using a random-effects model. Heterogeneity was assessed using the Cochrane Q test (p < 0.05) and the I(2) statistic (>50%). RESULTS: From 12 studies (450 patients), the pooled sustained virological response (SVR) was 71.4% (95% CI 64.7-77.4; Q statistic = 22.20, p = 0.023, I(2) = 50.44). The rapid virological response (RVR; 7 studies, 196 patients) was 47.4% (95% CI 40.6-54.7), and the early virological response (EVR; 9 studies, 283 patients) was 82.8% (95% CI 67.0-92.0). The probability of an SVR was 93.1% (95% CI 84.9-97.0) in those who obtained an RVR (6 studies, 82 patients) and 85.9% (95% CI 78.7-91.0) if an EVR (7 studies, 168 patients) was reached. CONCLUSION: Peginterferon with ribavirin is an effective option for treating acute HCV in HIV-positive patients, especially if they achieve an RVR or an EVR.

Sustained virologic response to standard interferon or pegylated interferon and ribavirin in patients with hepatitis C virus genotype 5: systematic review and meta-analysis of ten studies and 423 patients.

BACKGROUND: Interferon (IFN)-free therapy has vastly improved therapeutic options for those with hepatitis C virus infection (HCV). However, the lack of data and the expense limit its use for lesser known genotypes such as HCV-5, especially in countries with financial limitations. Previous reports estimate sustained virologic response (SVR) rates in HCV-5 to be ~40-70%. AIM: Our goal was to estimate pooled SVR rates for HCV-5 treatment-naïve patients treated with IFN or peginterferon (PEG IFN) and ribavirin (RBV) combination therapy for 48 weeks. METHODS: We conducted a literature search to identify articles with HCV-5 patients treated with IFN/PEG IFN + RBV. Pooled SVR rates were reported by random effects modeling with 95% confidence intervals. Heterogeneity was defined by the Cochrane Q-statistic p ≤ 0.05 and I(2) statistic ≥50%. RESULTS: A total of 423 patients from ten studies were included in the analysis. The pooled SVR rate for HCV-5 patients treated with IFN/PEG IFN + RBV for 48 weeks was 58.0% (CI 53.1%-62.7%). There was no evidence of heterogeneity (I(2) = 0, p = 0.61) or publication bias (Egger's test = 0.26). Pooled analysis of HCV-5 patients treated with PEG IFN + RBV was 55.0% (CI 49.4-61.5%). There was no evidence of heterogeneity (I(2) = 0.00, p = 0.75) or publication bias (Egger's test = 0.71). Combination therapy with IFN/PEG IFN + RBV had a pooled EVR of 90.2% (CI 76.8-96.2%). CONCLUSIONS: SVR for HCV-5 treated with combination therapy (IFN/PEG-IFN + RBV for 48 weeks) was approximately 60%. Current data are insufficient to evaluate variable duration of treatment (24 vs. 48 weeks), presence or absence of cirrhosis, effects of high versus low viral loads, or degree of fibrosis. The optimal treatment duration for HCV-5 patients with IFN-based combination remains to be established. Data and drug access are needed for treatment for HCV-5 in more resource-limited areas.

Meta-analysis: superior treatment response in Asian patients with hepatitis C virus genotype 6 versus genotype 1 with pegylated interferon and ribavirin.

OBJECTIVE: Our goal was to systematically and quantitatively assess treatment response between Asian patients with hepatitis C virus genotype 6 (HCV-6) and hepatitis C virus genotype 1 (HCV-1) treated for 48 weeks with pegylated interferon and ribavirin. METHODS: We performed a literature search in MEDLINE and EMBASE for 'genotype 6' in August 2013. Additional abstracts from major international scientific conferences from 2012 to 2013 were reviewed. Studies included were original articles with ≥10 treatment-naïve Asian HCV-6 patients. Exclusion criteria were coinfections with hepatitis B virus, HIV and/or other liver diseases. Heterogeneity was defined as a Cochrane Q test with a p value of 0.10 and an I(2) statistic of >50%. RESULTS of a random-effects model are reported. RESULTS: A total of 1,046 (503 HCV-6; 543 HCV-1) patients from 12 studies were included in the analysis. The pooled sustained virologic response (SVR) rate was 80.2% (95% CI 74.3-85.0, Q statistic = 20.87, p < 0.035; I(2) = 47.3%) for HCV-6 and 62.5% (95% CI 41.9-79.4, Q statistic = 52.41, p < 0.001; I(2) = 92.37) for HCV-1 patients. HCV-6 patients had a significantly higher SVR rate compared to HCV-1 patients (odds ratio 2.73, 95% CI 1.69-4.41, p < 0.001). Approximately one fourth of patients without early virologic response (EVR) achieved SVR, regardless of genotype (HCV-1, n = 6/23; HCV-6, n = 4/21). CONCLUSIONS: Asian patients with HCV-6 can expect higher SVR rates (∼80%) than HCV-1 patients (∼63%). EVR as a stopping rule is less clear in Asian patients with HCV-6 and HCV-1.

Crusted scabies of the scalp in a patient with systemic lupus erythematosus.

BACKGROUND: Crusted scabies is a severe, hyperkeratotic, psoriasiform disorder associated with immune suppression. Affected individuals typically present with crusted hyperkeratotic lesions in a variety of locations. This condition can lead to severe complications: institutional outbreaks and secondary bacterial infections associated with sepsis and high mortality. MAIN OBSERVATIONS: A 37-year-old woman with a 12-year history of systemic lupus erythematosus treated with prednisone, methotrexate, and plaquenil presented with a three-week history of a painful scalp rash with adherent yellow scale. Skin biopsy and tissue culture were consistent with a diagnosis of crusted scabies with superficial bacterial infection. The patient was treated with oral ivermectin and permethrin cream, as well as ciprofloxacin for the bacterial infection. At one-week follow-up, the scalp was no longer tender and hyperkeratotic plaques had significantly improved. At one-month follow-up, the affected scalp demonstrated further improvement with decreasing erythema and alopecia with follicular ostia. CONCLUSIONS: Our case highlights the atypical presentation of crusted scabies with primary scalp involvement and need for vigilance in recognizing and appropriately treating this condition to prevent the consequences of longstanding infection. Combination treatment with ivermectin and permethrin is appropriate management for this condition.

Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin.

The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11 102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ∼50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with pegylated interferon and ribavirin is superior to 24 weeks.

BACKGROUND: Hepatitis C virus genotype 6 (HCV-6) is common in patients from Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6 is unknown given the inconclusive evidence from studies with varying methodologies and small sample sizes. METHODS: A literature search for 'genotype 6' in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/liver conferences in 2012/2013. Inclusion criteria were original studies with ≥10 HCV-6 treatment-naïve patients treated with pegylated interferon + ribavirin (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV genotypes, and/or other liver diseases. Primary outcome was pooled sustained virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value of 0.10) and I (2) statistic (≥50 %). RESULTS: A total of 13 studies with 641 patients were included. The pooled SVR estimate was 77 % (CI 70-83 %) (Q value = 38.4, p value <0.001, I (2) = 68.7 %) overall, 79 % (CI 73-84 %) for the 48-week group and 59 % (CI 46-70 %) for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 versus 24 weeks, OR 1.9 (CI 1.08-3.2, p = 0.026). In studies with direct comparison of patients with rapid virologic response (RVR), there was no difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65-4.64, p = 0.27). CONCLUSION: Hepatitis C virus genotype 6 patients should be treated for 48 weeks, and those who achieve RVR may receive the shorter 24-week treatment duration. The high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective option for HCV-6 patients from resource-poor regions.