Advances in understanding and treating liver diseases during pregnancy:A review

Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal survival.It includes pre-eclampsia;eclampsia;haemolysis,elevated liver enzymes,and low platelets syndrome;acute fatty liver of pregnancy;hyperemesis gravidarum;and intrahepatic cholestasis of pregnancy.Recent basic researches have shown the various etiologies involved in this disease entity.With these advances,rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival.The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention.Therefore,correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis.Therefore,here we review and summarized recent advances in understanding the etiologies,clinical courses and management of liver disease in pregnancy.This information will contribute to physicians for diagnosis of disease and optimum management of patients.

Management of gastric and duodenal neuroendocrine tumors

Gastrointestinal neuroendocrine tumors(GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs(G-NETs) and duodenal NETs(D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type?Ⅰ, Ⅱ, and Ⅲ. Type?Ⅰ?G-NETs, which are the most common subtype(70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type Ⅱ G-NETs(5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome(MEN1-ZES). Both type?Ⅰ?and Ⅱ G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type Ⅲ G-NETs(10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type Ⅲ G-NETs, while endoscopic resection and followup, which are acceptable for the treatment of most type?Ⅰ?and Ⅱ G-NETs, are only acceptable for small and well differentiated type Ⅲ G-NETs. D-NETs include gastrinomas(50%-60%), somatostatin-producing tumors(15%), nonfunctional serotonin-containing tumors(20%), poorly differentiated neuroendocrine carcinomas(< 3%), and gangliocytic paragangliomas(< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs(G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.

Diversion colitis and pouchitis: A mini-review

Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment; however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients

The aging of the organ function causes sensitivity to the disease progression and need careful consideration for the medical treatment. With the increase of aging population, the opportunity to provide medical treatment for people in very old age is rapidly increasing therefore, the understanding of the various physiological changes of cellular function, size and function of organs are essential for the decision of therapeutic options. Among the various chronic conditions seen in elderly people, we have focused on liver cirrhosis, since despite specific therapeutic options for many of liver diseases including direct acting antivirals for hepatitis C virus, nucleoside analogs for hepatitis B, and corticosteroids for autoimmune hepatitis, there is currently no standard therapy to treat liver cirrhosis, which is the final stage of these liver diseases. Therefore,management of the various symptoms of liver cirrhosis is essential, and agingrelated parameters must be considered in the decision making for therapeutic strategies and dosage of the available medicine. In this mini-review, we have summarized the therapeutic options to manage various symptoms of liver cirrhosis, carefully considering the physiological changes of various organs associated with aging.

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication

The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori(H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection(ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies.The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy(NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritislike"appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H.pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature

BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.

Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment

Esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into three types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former two disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, particularly when it is located closer to the oral orifice. Since the condition itself is not malignant,minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including peroral endoscopic myotomy(POEM). However,the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. In this paper, we review the pathophysiology of each type of diverticulum and the current state-of-the-art treatment based on our experience.

Spontaneous regression of hepatocellular carcinoma: A mini-review

Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively amo ng t he 15 c as e s f or w hic h t he inf o r mat io n regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

Rational arrangement of measuring shear wave speed in the liver

BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.

Autonomic nervous system network and liver regeneration

To date, various signal transducers, cytokines, growth factors, and hormones have been reported to play an important role in homeostasis of various organs. Various cells and organs are involved in the hepatic regeneration process, which proceeds as a result of the coordination of many factors. While these factors are well known to be involved in the liver regeneration after the liver injury, however, as the details of such mechanisms have not been sufficiently elucidated, the practical applicability of hepatic regeneration based on the action of these and cytokines growth factors is still unclear. In terms of the involvement of the autonomic nervous system in hepatic regeneration, cell proliferation resulting from direct signal transduction to the liver has also been reported and recent studies focusing on the inter-organ communication via neural network opened a novel aspect of this field for therapeutic applicability. Therefore, the appropriate understanding of the relationship between autonomic neural network and liver regeneration through various organs including brain, afferent nerve, efferent nerve, etc. is essential. This mini-review explains the principle of neural system involved in the inter-organ communication and its contribution on the liver regeneration upon the liver injury reviewing recent progress in this field.

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vectormediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

Vonoprazan 20 mg vs lansoprazole 30 mg for endoscopic submucosal dissection-induced gastric ulcers

AIM To compare the healing effects of vonoprazan and lansoprazole on gastric ulcers induced by endoscopic submucosal dissection(ESD).METHODS Data were obtained from a total of 26 patients.Fourteen patients were randomized to the vonoprazan group and 12 were randomized to the lansoprazole group.Patients were administered either 20 mg vonoprazan or 30 mg lansoprazole per day after ESD.Endoscopic images just after ESD,on day 8,and on day 28 were used for the evaluation of the shrinking rate of ESD ulcers.The shrinking rates and the incidence of delayed bleeding were compared between the 2 groups.RESULTS The shrinking rates of ESD ulcers on day 8 [vonoprazangroup: 61.8%(range: 24.0%-91.1%),lansoprazole group: 71.3%(range: 25.2%-88.6%)] and on day 28 [vonoprazan group: 95.3%(range: 76.2%-100%),lansoprazole group: 97.2%(range: 81.1%-99.8%)] were not statistically different between the 2 groups.On day 28,most of the ulcers in both groups healed to more than 90%,whereas 3 of 14(21.4%) in the vonoprazan group and 1 of 12(8.3%) in the lansoprazole group had delayed ulcer healing,which was not statistically different(P = 0.356).The frequency of delayed bleeding was 0 in the both groups.Taken together,there were no significant differences between the two drug groups.CONCLUSION Our study indicates that vonoprazan is potent for the management of ESD ulcers although lansoprazole is also sufficient and cost-effective.

Collagenous gastritis: Review

Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands thicker than 10 μm and the infiltration of inflammatory mononuclear cells in the lamina propria. Collagenous colitis and collagenous sprue have similar histological characteristics to collagenous gastritis and are thought to be part of the same disease entity. However, while collagenous colitis has become more common in the field of gastroenterology, presenting with clinical symptoms of chronic diarrhea in older patients,collagenous gastritis is rare. Since the disease was first reported in 1989, only 60 cases have been documented in the English literature. No safe and effective treatments have been identified from randomized, controlled trials. Therefore, better understanding of the disease and the reporting of more cases will help to establish diagnostic criteria and to develop therapeutic strategies. Therefore, here we review the clinical characteristics, endoscopic and histological findings, treatment, and clinical outcomes from case reports and case series published to date, and provide a summary of the latest information on the disease. This information will contribute to improved knowledge of collagenous gastritis so physicians can recognize and correctly diagnose the disease, and will help to develop a standard therapeutic strategy for future clinical trials.

Diagnosis and management of fibromuscular dysplasia and segmental arterial mediolysis in gastroenterology field: A mini-review

The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia(FMD) and segmental arterial mediolysis(SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.RESULTS In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo E.CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.

Impact of continuous positive airway pressure therapy for nonalcoholic fatty liver disease in patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea(OSA)has been suggested as an independent risk factor for nonalcoholic fatty liver disease(NAFLD),and continuous positive airway pressure(CPAP)is the first-line therapy for OSA.AIM To clarify the efficacy of effective CPAP therapy on NAFLD of OSA patients by serum markers and transient elastography(TE)using FibroScan®(Echosens,Paris,France).METHODS We prospectively enrolled 123 consecutive patients with OSA who met the indications for CPAP.Liver fibrosis and steatosis were assessed using TE.Before and after 6 mo of CPAP therapy,serum markers and TE were assessed for all patients.The mean usage rate of CPAP therapy for 6 mo was arbitrarily calculated in each patient and expressed as“mean compliance index”(m-CI).RESULTS In 50 OSA patients with NAFLD,both aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were significantly decreased after 6 mo of CPAP therapy.Univariate analysis showed that decreased body weight(BW),decreased body mass index(BMI),decreased AST level,decreased hemoglobin A1c,and high m-CI were significantly related with improved ALT level.In multivariate regression model adjusted for quantities of BW change during 6 mo of CPAP therapy,high m-CI tended to improve ALT level(P=0.051).All 17 OSA patients with NAFLD,high m-CI and no BMI changes showed significant improvements in AST and ALT levels.Meanwhile,no significant changes in TE data or serum fibrosis markers were seen.CONCLUSION Some NAFLD could be associated with chronic intermittent hypoxia due to OSA independent of BW changes.In those cases,adequate reoxygenation from effective CPAP therapy may improve NAFLD.

Colorectal neuroendocrine carcinoma: A case report and review of the literature

BACKGROUND Colorectal neuroendocrine carcinoma (NEC) is a rare tumor that demonstrates aggressive growth pattern with ingrowth into the tract, metastasis to the other organs, and invasion to the surrounding organs;these clinical characteristics result in poor prognosis. Surgical resection appears as an effective approach;however, because it is difficult to accurately diagnose NEC during the early stage and owing to its aggressive growth pattern, development of a reliable standard chemotherapy regimen and management strategies are essential. CASE SUMMARY Here, we report the case of patient with NEC showing an aggressive growth pattern that resulted in the rupture of the tumor to the outside the colon after stenting of the internal colonic stenosis. In addition, the tumor invaded into the duodenum, thereby causing duodenal stenosis that required an additional stent in the duodenum. This aggressive growth pattern is one of the main features of the NEC that is different from adenocarcinoma. To clarify the clinical characteristics, we reviewed 60 recently reported cases, including data on tumor location, size, treatment, and prognosis. CONCLUSION We consider that the information presented here is of great significance for the diagnosis, treatment, and management of symptoms of the patients with NEC.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

Duodenal gastrointestinal stromal tumors(GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography(EUS) and fine-needle aspiration(FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C

AIM To evaluate and compare the efficacy and safety of telaprevir(TVR)-and simeprevir(SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older.METHODS The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin(RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years(range: 28-65 years) in the younger group and 69 years(range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years(range: 36-65 years) in the younger group and 71 years(range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment.RESULTS Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response(SVR) was found between the younger(80.8%) and older(88.2%) groups. The SVR rates for patients with the interleukin 28B(IL28B)(rs8099917) TG/GGgenotypes(73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype(86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period(as a percentage of the target dose) was significantly higher in the younger group than in the older group(91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups(91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B(OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV(> 60%)(OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger(81.1%) and older(82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes(77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28 B TT-genotype(88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR(OR = 9.677; 95%CI:1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively.CONCLUSION Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.