小分床处理工艺与发电机定冷水处理

发电机定冷水水质与发电机的对地绝缘性能和铜线棒的腐蚀速率密切相关,定冷水处理工艺的优劣直接影响机组的运行安全。随着《大型发电机内冷却水质及系统技术要求(DL/T801—2010)》在2011年5月发布和执行,对大型机组发电机定冷水系统非密闭运行时的定冷水水质提出了更高的要求:p H 8.0~9.0,电导率0.4~2.0μS/cm(25℃),铜离子浓度低于20μg/L。采用小分床处理工艺SZSY-3发电机定冷水处理装置,能满足大型机组定冷水质要求。

定冷水小分床处理工艺再生探索

发电机定冷水水质与发电机的对地绝缘性能和铜线棒的腐蚀速率密切相关,定冷水处理工艺的优劣直接影响机组的运行安全。随着《大型发电机内冷却水质及系统技术要求(DL/T801-2010)》在2011年5月发布和执行,对大型机组发电机定冷水系统非密闭运行时的定冷水水质提出了更高的要求,pH值8.0~9.0,电导率0. 4~2. 0μS/cm (2 5℃),铜离子浓度低于2 0μg/L。采用小分床处理工艺SZSY-3发电机定冷水处理装置能满足大型机组pH值8.0~8.9,电导率0.4~2.0μS/cm(25℃),铜离子浓度低于20μg/L。而定冷水小分床再生装置可对小分床内树脂进行体外再生,从而实现树脂的重复利用,提高小分床的使用寿命。

Differentiation of Crohn’s disease from intestinal tuberculosis in India in 2010

Differentiating intestinal tuberculosis from Crohn’s disease (CD) is an important clinical challenge of considerable therapeutic significance. The problem is of greatest magnitude in countries where tuberculosis continues to be highly prevalent, and where the incidence of CD is increasing. The final clinical diagnosis is based on a combination of the clinical history with endoscopic studies, culture and polymerase chain reaction for Mycobacterium tuberculosis, biopsy pathology, radiological investigations and response to therapy. In a subset of patients, surgery is required and intraoperative findings with pathological study of the resected bowel provide a definitive diagnosis. Awareness of the parameters useful in distinguishing these two disorders in each of the different diagnostic modalities is crucial to accurate decision making. Newer techniques, such as capsule endoscopy, small bowel enteroscopy and immunological assays for Mycobacterium tuberculosis, have a role to play in the differentiation of intestinal tuberculosis and CD. This review presents currently available evidence regarding the usefulness and limitations of all these different modalities available for the evaluation of these two disorders.

Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines

AIM： To evaluate determinants of infammatory mark-ers in chronic renal failure patients according to the level of glomerular fltration rate. METHODS： One hundred ffty four patients （Age： 44 ± 06 years; male/female： 66/88） with chronic renal fail-ure （CRF） were divided into 6 groups according to the National Kidney Foundation （NKF） classification. They included 28 primary stage renal failure patients （CRF 1）, 28 moderate stage renal failure patients （CRF 2）,28 severe stage renal failure patients （CRF 3）, 18 end-stage renal failure patients （CRF 4）, 40 hemodialysis （HD） patients, and 12 peritoneal dialysis （PD） patients. Tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, interleukin-6 （IL-6） and C-reactive protein （CRP） were analyzed by immunosorbent assay kit （ELISA） （Cayman Chemical’s ACETM EIA kit）. Immunoassay methods were used for total homocysteine （tHcy） （fuorescence polarization immunoanalysis HPLC, PerkinEmer 200 series）, transferrin （MININEPHTM human transferin kit： ZK070.R）, ferritin （ADVIA Centaur ） and fbrinogen analysis （ACL 200）. Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.RESULTS： Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD （16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P 〈 0.001） and PD （14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P 〈 0.001）. IL-1β levels were increased in HD （9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P 〈 0.001） and CRF 4 （7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P 〈 0.001） patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD （32.27 ± 12.08 μmol/L） and PD （28.37 ± 4.98 μmol/L） patients compared to the other groups of CRF （P 〈 0.001）. The serum CRP level was signifcantly increased in HD （18.17 ± 6.38 mg/L） and PD （17.97 ± 4.85 mg/L） patients compared to the other groups of CRF patients （P 〈 0.001）. The plasma fbrinogen level was more elevated in HD （6.86 ± 1.06 g/L） and CRF 4 （6.05 ± 0.57 g/L） than in the other groups （ P 〈 0.001）. Furthermore; the ferritin level was higher in HD （169.90 ± 62.16 ng/mL） and PD （90.08 ± 22.09 ng/mL） pa-tients compared to the other groups of CRF （P 〈 0.001）. The serum transferrin value was signifcantly decreased especially in PD （1.78 ± 0.21 g/L） compared to the oth-er groups （P 〈 0.001）. We found a negative correlation between glomerular fltration rate （GFR）, TNF-α levels （ r = -0.75, P 〈 0.001）, and tHcy levels （ r = -0.68, P 〈 0.001）. We observed a positive correlation between GFR and transferrin levels （ r = 0.60, P 〈 0.001）. CONCLUSION： CRF was associated with elevated in-flammatory markers. The inflammation was observed at the severe stage of CRF and increases with progres-sion of renal failure.

Therapeutic target for nephrotic syndrome: Identification of novel slit diaphragm associated molecules

The slit diaphragm bridging the neighboring foot pro-cesses functions as a fnal barrier of glomerular capil-lary wall for preventing the leak of plasma proteins into primary urine. It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases. Neph-rin, a gene product of NPHS1, a gene for a congenital nephrotic syndrome of Finnish type, constitutes an ex-tracellular domain of the slit diaphragm. Podocin was identified as a gene product of NPHS2 , a gene for a familial steroid-resistant nephrotic syndrome of French. Podocin binds the cytoplasmic domain of nephrin. After then, CD2 associated protein, NEPH1 and transient re-ceptor potential-6 were also found as crucial molecules of the slit diaphragm. In order to explore other novel molecules contributing to the development of protein-uria, we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside ne-phropathy, a mimic of a human minimal change type nephrotic syndrome. Then we have found that synaptic vesicle protein 2B, ephrin-B1 and neurexin were already downregulated at the early stage of puromycin aminonucleoside nephropathy, and that these molecules were localized close to nephrin. It is conceivable that these molecules are the slit diaphragm associated molecules, which participate in the regulation of the barrier func-tion. These molecules could be targets to establish a novel therapy for nephrotic syndrome.

Primary glomerular diseases in the elderly

Primary glomerular diseases in the elderly population are a frustrating topic due to difficulties in both the diagnosis and decision making about treatment. The most frequent type of primary glomerular disease in elderly is membranous nephropathy; while its counterpart in younger population is Ig A nephropathy. The most frequent cause of nephrotic syndrome in the elderly is also membranous nephropathy. Pauci-immune crescentic glomerulonephritis(GN) rate increases both in elderly and very elderly population. Pauci-immune crescentic GNs should be regarded as urgencies in elderly patients as in their younger counterparts due to potential for causing end-stage renal disease in case of delayed diagnosis and treatment, and also causing mortality due to alveolar hemorrhage in patients with pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the elderly as in all other age groups. Renal biopsy prevents unnecessary treatments and provides prognostic data. So advanced age should not be the sole contraindication for renal biopsy. The course of primary glomerular diseases may differ in the elderly population. Acute kidney injury is more frequent in the course and renal functions may be worse at presentation. These patients are more prone to be hypertensive. The decision about adding immune suppressive therapies to conservative methods should be made considering many factors like co-morbidities, drug side effects and potential drug interactions, risk of infection, patient preference, life expectancy and renal functions at the time of diagnosis.

Searching for a treatment for Alport syndrome using mouse models

Alport syndrome （AS） is a hereditary nephritis caused by mutations in COL4A3, COL4A4 or COL4A5 encod-ing the type IV collagen α3, α4, and α5 chains, which are major components of the glomerular basement membrane. About 20 years have passed since COL4A3, COL4A4, and COL4A5 were identifed and the frst Al-port mouse model was developed using a knockout ap-proach. The phenotype of Alport mice is similar to that of Alport patients, including characteristic thickening and splitting of the glomerular basement membrane. Alport mice have been widely used to study the patho-genesis of AS and to develop effective therapies. In this review, the newer therapies for AS, such as pharma-cological interventions, genetic approaches and stem cell therapies, are discussed. Although some stem cell therapies have been demonstrated to slow the renal disease progression in Alport mice, these therapies demand continual refnement as research advances. In terms of the pharmacological drugs, angiotensin-con-verting enzyme inhibitors have been shown to be effec-tive in Alport mice. Novel therapies that can provide a better outcome or lead to a cure are still awaited.

Update on immunoglobulin A nephropathy, Part I: Pathophysiology

Immunoglobulin A （IgA） nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identifed even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 （IgA1） with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarifed. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarifed.

Reclassification of membranoproliferative glomerulonephritis:Identification of a new GN:C3GN

This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

Hepcidin-25 negatively predicts left ventricular mass index in chronic kidney disease patients

AIM： To assess the correlation between the serum hep-cidin-25 level and left ventricular mass index.METHODS： This study was a cross-sectional study conducted between March 2009 and April 2010. Demo-graphic and biochemical data, including the serum hep-cidin-25 level, were collected for chronic kidney disease （CKD） patients. Two-dimensional echocardiography was performed to determine the left ventricle mass （LVM）, left ventricular mass index （LVMI）, interventricular septum thickness （IVSd）, left ventricle posterior wall thickness （LVPW）, right ventricular dimension （RVD）, left atrium （LA） and ejection fraction （EF）.RESULTS： A total of 146 patients with stage 1 to 5 CKD were enrolled. Serum hepcidin-25 levels were 16.51 ± 5.2, 17.59 ± 5.32, 17.38 ± 6.47, 19.98 ± 4.98 and 22.03 ± 4.8 ng/mL for stage 1 to 5 CKD patients, respectively. Hepcidin-25 level was independently pre-dicted by the serum ferritin level （β = 0.6, P = 0.002） and the estimated glomerular fltration rate （β = -0.48, P = 0.04）. There were negative correlations between the serum hepcidin level and the LVM and LVMI （ P = 0.04 and P = 0.005, respectively）. Systolic blood pressure （BP） was positively correlated with the LVMI （ P = 0.005）. In the multivariate analysis, a decreased serum hepci-din-25 level was independently associated with a higher LVMI （β = -0.28, 95%CI： -0.48 - -0.02, P = 0.006） after adjusting for body mass index, age and systolic BP.CONCLUSION： A lower serum hepcidin level is associ-ated with a higher LVMI in CKD patients. Low hepcidin levels may be independently correlated with unfavor-able cardiovascular outcomes in this population.

Pathogenesis of glomerular haematuria

Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidneydisease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells （RBCs） with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological fndings.

Urgent call for reconsideration of chronic kidney disease

Circulating toxins namely： free radicals, cytokines and metabolic products induce glomerular endothelial dys-function, hemodynamic maladjustment and chronic ischemic state;this leads to tubulointerstitial fbrosis in chronic kidney disease （CKD）. Altered vascular homeo-stasis observed in late stage CKD revealed defective angiogenesis and impaired nitric oxide production ex-plaining therapeutic resistance to vasodilator treatment in late stage CKD. Under current practice, CKD patients are diagnosed and treated at a rather late stage due to the lack of sensitivity of the diagnostic markers avail-able. This suggests the need for an alternative thera-peutic strategy implementing the therapeutic approachat an early stage. This view is supported by the normal or mildly impaired vascular homeostasis observed in early stage CKD. Treatment at this early stage can potentially enhance renal perfusion, correct the renal ischemic state and restore renal function. Thus, this alternative therapeutic approach would effectively pre-vent end-stage renal disease.

Regulatory roles of nitric oxide and angiotensin Ⅱ on renal tubular transport

Renal tubules regulate blood pressure and humoral homeostasis. Mediators that play a significant role in regulating the transport of solutes and water include angiotensin Ⅱ （AngⅡ） and nitric oxide （NO）. AngⅡcan signifcantly raise blood pressure via effects on the heart, vasculature, and renal tubules. AngⅡ generally stimulates sodium reabsorption by triggering sodium and fuid retention in almost all segments of renal tu-bules. Stimulation of renal proximal tubule （PT） trans-port is thought to be essential for AngⅡ-mediated hy-pertension. However, AngⅡ has a biphasic effect on in vitro PT transport in mice, rats, and rabbits： stimulation at low concentrations and inhibition at high concentra-tions. On the other hand, NO is generally thought to inhibit renal tubular transport. In PTs, NO seems to be involved in the inhibitory effect of AngⅡ. A recent study reports a surprising fnding： AngⅡ has a mono-phasic stimulatory effect on human PT transport. De-tailed analysis of signalling mechanisms indicates that in contrast to other species, the human NO/guanosine 3’,5’-cyclic monophosphate/extracellular signal-regulat-ed kinase pathway seems to mediate this effect of Ang Ⅱ on PT transport. In this review we will discuss recent progress in understanding the effects of AngⅡ and NO on renal tubular transport.

Collapsing focal segmental glomerulosclerosis: Current concepts

Collapsing focal segmental glomerulosclerosis （cFSGS）, also known as collapsing glomerulopathy is currently classified under the rubric of FSGS. However, its de-fining morphological features are in stark contrast to those observed in most other variants of FSGS. During the early stage of the disease, the lesion is character-ized pathologically by an implosive segmental and/or global collapse of the glomerular capillary tufts, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. With advancement of the disease, segmental and/or global glomerulosclerosis is also observed in association with the collapsing le-sions. The etiology of this enigmatic disorder is still elusive, but a growing list of diseases/conditions is being reported in association with this morphological pattern of renal parenchymal injury. The pathogenesis of cFSGS involves discreet epithelial cell injury leadingto cell cycle dysregulation and a proliferative cellularphenotype. From the clinical perspective, cFSGS is no-torious for its propensity to affect black people, a highincidence and severity of nephrotic syndrome, markedresistance to empirical therapy, and rapid progressionto end-stage renal disease. The lesion has also beenreported in transplanted kidneys either as recurrent orde novo disease, frequently leading to graft loss. Mostcases have been reported in western countries, but the lesion is also being increasingly recognized in the tropi-cal regions. The recent increase in reporting of cFSGS partly refects a true increase in the incidence and part-ly a detection bias. There is no specifc treatment for the disorder at present. Newer insights into the patho-genesis may lead to the development of targeted and specifc therapy in near future. There is an urgent need to increase awareness of the lesion among pathologists and nephrologists, especially those from developing countries, to ensure accurate diagnosis and appropriate managment. With the accumulation of more and more data, it is hoped that the prevailing confusion about the nosological identity of the lesion will also be resolved in a more logical way.

INSTRUCTIONS TO AUTHORS

Podocytes covering the glomerular basement mem-brane over the glomerular capillary consist of three morphologically and functionally different segments, the cell body, major processes and extending finger-like foot processes （FPs）. The FPs of neighboring podo-cytes are connected by a continuous adherent junction structure named the slit diaphragm （SD）. The extracel-lular SD is linked to the intracellular, a highly dynamic, cytoskeleton through adaptor proteins. These adaptor proteins, such as CD2-associated protein, zonula oc-cludens 1, β-catenin, Nck and p130Cas, located at the intracellular SD insertion area near lipid rafts, have important structural and functional roles. Adaptor pro-teins in podocytes play important roles as a structural component of the podocyte structure, linking the SD to the cytoskeletal structure and as a signaling platform sending signals from the SD to the actin cytoskeleton. This review discusses the roles of adaptor proteins in the podocyte cytoskeletal structure and signaling from the SD to the actin cytoskeleton.

Wavelet analysis of pressure fluctuation signals in a gas-solid fluidized bed

It has been shown that much dynamic information is hidden in the pressure fluctuation signals of a gas-solid fluidized bed. Unfortunately, due to the random and capricious nature of this signal, it is hard to realize reliable analysis using traditional signal processing methods such as statistical analysis or spectral analysis, which is done in Fourier domain. Information in different frequency band can be extracted by using wavelet analysis. On the evidence of the composition of the pressure fluctuation signals, energy of low frequency (ELF) is proposed to show the transition of fluidized regimes from bubbling fluidization to turbulent fluidization. Plots are presented to describe the fluidized bed's evolution to help identify the state of different flow regimes and provide a characteristic curve to identify the fluidized status effectively and reliably.

Fanconi-Bickel syndrome as an example of marked allelic heterogeneity

Renal tubular acidosis （RTA） encompasses many re-nal tubular disorders characterized by hyperchloremic metabolic acidosis with a normal anion gap. Untreated patients usually complain of growth failure, osteoporo-sis, rickets, nephrolithiasis and eventually renal insuff-ciency. Fanconi-Bickel syndrome （FBS） is an example of proximal RTA due to a single gene disorder; it is caused by defects in the facilitative glucose transporter 2 gene that codes for the glucose transporter protein 2 ex-pressed in hepatocytes, pancreatic β-cells, enterocytes and renal tubular cells. It is a rare inherited disorder of carbohydrate metabolism manifested by huge hepa-tomegaly [hence it is classified as glycogen storage disease （GSD） type XI; GSD XI], severe hypophospha-temic rickets and failure to thrive due to proximal renal tubular dysfunction leading to glucosuria, phosphaturia, generalized aminoaciduria, bicarbonate wasting and hy-pophosphatemia. The disorder has been reported from all parts of Europe, Turkey, Israel, Arabian countries, Ja-pan and North America. Many mutant alleles have been described, its exact frequency is unknown and there is no single mutation found more frequently than the oth-ers. The presence of consanguinity in affected families suggests an autosomal recessive pattern of inheritance. New cases of FBS have been recently reported in the Middle and Far East in collaboration with specialized centers. Two novel mutations have been discovered in two unrelated Egyptian families. The first was two bases deletion, guanine and adenine, （c.253_254delGA） causing a frameshift mutation （p. Glu85fs） and the sec-ond is mutation in exon6 in splicing acceptor site with intron5 （c.776-1G〉C or IVS5-1G〉A）. Moreover, a new different mutation was described in a 3 year old Indian boy.

Species differences in regulation of renal proximal tubule transport by certain molecules

Renal proximal tubules （PTs） play important roles in the regulation of acid/base, plasma volume and blood pressure. Recent studies suggest that there are substantial species differences in the regulation of PT transport. For example, thiazolidinediones （TZDs） are widely used for the treatment of type 2 diabetes mellitus, but the use of TZDs is associated with fluid overload. In addition to the transcriptional enhancement of sodium transport in distal nephrons, TZDs rapidly stimulate PT sodium transport via a non-genomic mechanism depending onperoxisome proliferator activated receptor g/Src/epidermal growth factor receptor （EGFR）/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT transport probably due to constitutive activation of Src/EGFR/ERK pathway. This unique activation of Src/ERK may also affect the effect of high concentrations of insulin on mouse PT transport. On the other hand, the effect of angiotensin Ⅱ （Ang Ⅱ） on PT transport is known to be biphasic in rabbits, rats, and mice. However, Ang Ⅱ induces a concentration-dependent, monophasic transport stimulation in human PTs. The contrasting responses to nitric oxide/guanosine 3’,5’-cyclic monophosphate pathway may largely explain these different effects of Ang Ⅱ on PT transport. In this review, we focus on the recent fndings on the species differences in the regulation of PT transport, which may help understand the species-specific mechanisms underlying edema formation and/or hypertension occurrence.

Use of eltrombopag in thrombocytopenia of liver disease

Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.