Fanpu Ji

Dilated cardiomyopathy and hypothyroidism associated with pegylated interferon and ribavirin treatment for chronic hepatitis C: case report and literature review

Pegylated interferon alpha (Peg IFN-α) in combination with ribavirin is the backbone of treatment in chronic hepatitis C (CHC). Cardiotoxicity due to interferon therapy is rare. The most frequent cardiovascular complications are arrhythmias and ischemic manifestations. Cardiomyopathy is extremely rare but can be life threatening. We present the case of a 41-year-old female patient with CHC in whom Peg IFN-α induced dilated cardiomyopathy and hypothyroidism. Chest radiography showed an enlarged and globular cardiac silhouette and pulmonary congestion. Echocardiography showed decreased left ventricular systolic function with an ejection fraction of 32% and fractional shortening of 15%. Cardiomyopathy had a complete remission after cessation of antiviral therapy with short-term heart failure medications and supportive care. Then we review the current literature about interferon induced cardiomyopathy in patients with HCV infection, as well as share our clinical experience in diagnosing and managing this rare complication.

Baicalein protect pancreatic injury in rats with severe acute pancreatitis by inhibiting pro-inflammatory cytokines expression

BACKGROUND/AIM Inflammatory cytokines is a key point in the development of pathogenesis of SAP. Inflammatory mediators TNF-α and IL-6 are up-regulated in serum of patients with SAP and become good discriminators of SAP severity. MATERIALS AND METHODS In this study, we investigated the treatment effectiveness of Baicalein on SAP rat model. Baicalein was intravenously injected immediately after SAP induction in rats. The mortality, histopathology score, ascites fluid volume, and pro-inflammatory cytokine production were evaluated at 12 h after SAP induction. RESULTS Baicalein decreased the pancreatic histopathology score, reduced ascites fluid production, protected against pancreatic injury, and improved survival in rats with SAP. The serum IL-6 and TNF-α concentrations were also down-regulated by Baicalein. CONCLUSION Baicalein demonstrated a well curative capability on rats with SAP. The mechanism may be alleviateing pancreatic injury and inhibiting pro-inflammatory cytokines expression.

Splenectomy prior to antiviral therapy in patients with hepatitis C virus related decompensated cirrhosis

Patients with hepatitis C virus-related decompensated cirrhosis can benefit from interferon-based antiviral therapy, but the common complication of cytopenia is a contraindication for this treatment. Splenectomy prior to interferon therapy may alleviate this problem. To investigate whether splenectomy improves the efficacy of antiviral therapy, 13 interferon-naïve hepatitis C virus decompensated cirrhotic patients underwent splenectomy between January 2008 and January 2011, followed 1-3 months later by an interferon-based therapeutic regimen (pegylated/standard interferon-α combined with ribavirin for 48 weeks). Ten (76.9%) of the patients developed postoperative complications, which included minor portal vein thrombosis (2/13, 15.4%) and transient ascites (8/13, 61.5%). At one-month post-splenectomy, the patients showed significantly increased platelet (pre-surgery: 48.2±15.9 vs. 186.0±70.6×10(3)μL(-1), p<0.001) and leukocyte (2.1±0.5 vs. 5.7±1.4×10(3)μL(-1), p<0.001) counts. Eight (61.5%) of the patients achieved sustained virological response, including all HCV genotype 2a-infected patients (4/4, 100%) and some of the genotype 1b-infected patients (4/9, 44.4%). Temporary interferon-α suspension was required for one patient to address severe intestinal infection. These results indicate that splenectomy prior to interferon-based therapy was safe and may facilitate adherence to subsequent antiviral therapy in selected HCV cirrhotic patients with portal hypertension and hypersplenism.

Predictive factors for adverse dermatological events during pegylated/interferon alpha and ribavirin treatment for hepatitis C

BACKGROUND Treatment of chronic hepatitis C (CHC) with pegylated interferon-alpha/ribavirin is associated with well-characterized dermatological adverse events (AEs), which can lead to premature discontinuation of treatment. OBJECTIVE To investigate the incidence and spectrum of dermatological AEs during CHC treatment with interferon-alpha plus ribavirin and analyzed factors predisposing patients to such reactions. STUDY DESIGN Between January 2008 and December 2012, 152 CHC patients who had received interferon/pegylated interferon plus ribavirin therapy were enrolled in this retrospective study. To determine which factors were associated with dermatological AE development, a Cox proportional-hazards regression analysis was performed. RESULTS Thirty dermatological AEs were recorded in 28 (18.4%) patients. These reactions included 14 (9.2%) patients with eczematous reactions, four (2.6%) patients with xerosis, three (2.0%) patients with new-onset or exacerbation of psoriasis, two (1.3%) patients with lichenoid eruption, two (1.3%) patients with diffuse folliculitis and one patient with lichen planus, alopecia areata, hypermelanosis, and necrosis of the skin and toenails. Application of the Cox proportional-hazards model revealed that age older than 60 years (HR=1.070; 95% CI: 1.043-1.096), pre-existing anaphylaxis/skin disease (HR=2.612; 95% CI: 1.593-3.324), cirrhosis (HR=1.863; 95% CI: 1.047-3.013), and treatment with pegylated interferon formulations (HR=1.930; 95% CI: 1.052-3.687) were associated with occurrence of dermatologic AEs. Twenty-seven (90%) skin conditions were classified as mild to moderate, while one case (3.3%) warranted premature discontinuation of treatment. CONCLUSION Dermatological AEs resulting from interferon-alpha/ribavirin treatment of CHC contribute to a wide spectrum involve the skin, mucous membrane, hair, and nails. These dermatological AEs correlated with older age, previous skin condition, cirrhosis, and use of pegylated interferon formulations.

Eltrombopag for Thrombocytopenic Patients With Hepatitis C Virus Infection and Cirrhosis

Dear Editor: We read with great interest the paper by Afdhal and colleagues, which was recently published by Gastroenterology. In their large-scale, multicenter, phase 3 randomized, controlled studies, the authors presented important data regarding the ability of eltrombopag to increase platelet numbers in thrombocytopenic patients with hepatitis C virus (HCV) and advanced fibrosis and cirrhosis; this therapeutic effect led to significantly increased rates of sustained virological response (SVR) in the eltrombopag treatment groups (vs placebo groups) of both the ENABLE-1 and ENABLE-2 study cohorts (SVR rates: 23% vs 14% and 19% vs 13%, respectively). Although we agree that these findings support the potential use of eltrombopag as an adjunct for pegylated-interferon alfa (PEG-IFNa) and ribavirin combination antiviral therapy in patients with cirrhosis and thrombocytopenia, we have several comments on the study. Firstly, the SVRs achieved by PEG-IFNa and ribavirin therapy in previous studies of HCV patients with portal hypertension were 35.1% (16.0% with genotype 1⁄4, and 56.8% with genotype 2 ⁄3) and 26% (14% with genotype 1 and 48 % with genotype 2). These SVR rates are noticeably higher than those reported for the eltrombopag and placebo groups (even including 15%–19% patients from south-east Asia in their study), but not a comparable low SVR rate of 13% in placebo group as described in the Discussion section. One possible explanation for the higher SVR rates may be that the researchers did not reduce the dose of or discontinue PEG-IFNa in accordance with product labels; in fact, low baseline platelet count made considerable patients ineligible or marginal candidates for PEG-IFNa therapy before included in the studies. Secondly, the approval of the HCV protease inhibitors telaprevir and boceprevir in 2011 represents a major breakthrough in the treatment of chronic hepatitis C. Studies of telapreviror boceprevir-based combination therapies with PEG-IFNa and ribavirin have shown significantly higher SVR rates achieved in patients with HCV genotype 1 infection and advanced fibrosis/cirrhosis. Afdhal et al suggested that eltrombopag should be evaluated in the treatment regimens with triple therapies or quadruple therapies in patients with cirrhosis and thrombocytopenia. However, the reported safety profile of the triple therapy is poor; platelet count <100,000/ mm3 was identified as a risk factor of death or severe complications, leading to a recommendation against cirrhotic patients with platelet count <100,000/mm3

Simultaneous occurrence of pleural effusion and interstitial pneumonitis after treatment with pegylated interferon for hepatitis C virus infection.

Combination of pegylated interferon and ribavirin has been the standard program for hepatitis C virus (HCV) infection. Pulmonary complications, although uncommon, have been reported in association with the use of interferon, and pleural effusion is rare. We report the second case of pleural effusion and interstitial pneumonitis in a patient treated with pegylated interferon and ribavirin for chronic HCV infection. The respiratory symptoms of our patient continued to progress even though the treatment with pegylated interferon had been withdrawn, but the symptoms improved dramatically following treatment with steroids.

Hypogenesis of the right hepatic lobe and associated Chilaiditi sign

Agenesis or hypogenesis of the right liver lobe is an extremely rare congenital anomaly and one of the rare causes of Chilaiditi sign or syndrome. We report a case of Chilaiditi sign associated with the congenital anomaly. A 45-year-old male patient with a 15-year history of hepatitis B virus (HBV) infection was admitted for fatigue. He had no abdominal surgery or trauma history, nor any medications history. The physical examination was unremarkable. Apart from positive serum HBV markers, the laboratory values were normal. The chest radiograph showed a distended loop of large intestine below an elevated right hemidiaphragm (Fig. 1a). Abdominal computed tomography showed hepatodiaphragmatic colonic interposition, segmental agenesis of the right lobe of the liver with enlarged left hepatic lobe, isolated portal vein (Fig. 1b, arrow), and the inferior vena cava pass through caudate lobe and the remains right hepatic lobe (Fig. 1c, arrow). Agenesis or hypogenesis of the right liver lobe is considered to be causedbya failureof the rightportalvein todevelop,oranerrorofmutual induction between the primitive diaphragm and the endodermal diverticulum representing the primitive liver. Hepatodiaphragmatic interposition of the intestine, known as Chilaiditi sign or syndrome, was first described by Demetrius Chilaiditi in 1910, with an incidence of 0.025– 0.28%. Patients with Chilaiditi sign are asymptomatic, while patients present symptoms such as abdominal pain, bloating, nausea, vomiting, changes in intestinal habits, substernal pain, even dyspnoea and cardiac arrhythmias, named Chilaiditi syndrome. Predisposing factors include absence of the normal suspensory ligaments of the transverse colon, redundant colon, right hemidiaphragm elevation, atrophy or hypogenesis of the right hepatic lobe, etc. The differential diagnoses of Chilaiditi syndrome include pneumoperitoneum, diaphragmatic hernia, subdiaphragmatic abscess, bowel obstruction and volvulus. No intervention is required for an asymptomatic patient with Chilaiditi sign, as well as congenital anomaly of the liver. The hallmark of therapy of Chilaiditi syndrome is conservative, and rarely has surgical intervention been indicated.

Individual surveillance using model-based hepatocellular carcinoma risk estimates in chronic hepatitis C patients after antiviral treatment

To the Editor: We read with interest the article by Ioannou and colleagues in which they discussed using a risk-based model to estimate the risk of hepatocellular carcinoma (HCC) after antiviral treatment for hepatitis C virus (HCV) infection. A shortened surveillance interval (6-month vs. 3-month) after sustained virologic response (SVR) has been suggested in order to diagnose HCC-related tumors at a lower stage and a smaller size, allowing for curative treatment which improves survival and reduces recurrence rates after treatment of HCC. However, the cost-effectiveness of frequent HCC surveillance for individuals after antiviral treatment remains unclear, particularly during the era of direct-acting antiviral therapy when the number of HCV-infected patients who achieve SVR has increased dramatically. Therefore, it is very important to accurately stratify the risks of HCC development in patients who received antiviral treatments using a simple and noninvasive method to guide individualized monitoring. In this article, Ioannou and colleagues have performed an excellent study using data obtained from a US cohort of the Veterans Affairs Health Care System to develop and internally validate 4 models to predict HCC following antiviral treatment based on cirrhosis and SVR status. Their study showed that using model-based HCC risk estimates to determine whether to recommend screening/surveillance or not demonstrated a higher net benefit compared to the screen-all or screen-none strategies recommended by current HCC guidelines. These models are very important and will potentially help clinicians to customize HCC surveillance strategies in individual patients; however, the risk of HCC is complex and requires additional considerations. Firstly, to predict HCC in patients after antiviral treatment, the use of post-treatment laboratory measurements would be better than using pre-treatment measurements. This point has been discussed in previous studies which showed that posttreatment aspartate aminotransferase-to-platelet ratio index (APRI) and alpha-fetoprotein (AFP) better reflected the actual liver diseases status and risk of HCC development. Thus, we suggest that post-treatment AFP and APRI levels are more reliable surrogate markers to predict HCC. Secondly, the authors suggested risk-based HCC surveillance among patients even without cirrhosis who had additional ‘‘adverse characteristics”. We agree with the authors recommendation of using age as a variable for a surveillance decision, since older age is one of the risk factors of HCC development. However, HCV-infected individuals without cirrhosis had a much lower HCC risk, especially in the younger patients. In the model for no cirrhosis/no SVR subgroup, the high estimated risk of HCC may be attributable to pre-treatment parameters (low platelets and high aspartate/alanine aminotransferase

Seasonality of cellulitis: evidence from Google Trends

Introduction According to our clinical experience, cellulitis is common in summer; however, very few studies have mentioned this trend. Methods Using Google Trends, we analyzed the monthly data of Google searches for “cellulitis” from 31 countries on 6 continents. Results Seasonality explained 34%–92% of the variability in search volume, with peaks occurring in summer months. Conclusion The analyses offered new insights into the epidemiology of cellulitis on national and international scales. Clinical data are needed to validate the Internet search data.

Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four pregnant Chinese women

Hantavirus infection during pregnancy can influence both maternal and fetal outcomes. Here, we describe four cases of hemorrhagic fever with renal syndrome (HFRS) in pregnant Chinese women. The HFRS put these women at increased risk for severe illness, despite the patients’ symptomologies in the onset phase were similar to those observed in non‐pregnant HFRS patients, such as fever, headache, nausea, and thrombocytopenia. Pregnant women appeared to have a more severe status, presenting with severe complications, such as hypervolemia and pulmonary edema. Nevertheless, with appropriate management, mothers with HFRS may carry to full‐term and breastfeeding maybe safe and feasible.