Association between IL-37 gene polymorphisms and risk of HBV-related liver disease in a Saudi Arabian population.

Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.

The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease.

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.

Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBV-infected patients.

Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combinational mutations in HBx gene on the pathogenesis of HCC during progressive stages of liver disease. The patients were categorized into inactive HBV carriers, active carriers, cirrhosis and HCC groups based on disease severity. Male sex, age > 50 years, and high serum alanine aminotransferase level were associated with risk of progressive liver disease. I127T, V131I, and F132Y/I/R mutations showed a significant increasing trend associated with the disease progression to HCC. H94Y and K130M mutations were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed, with significant rising prevalence through progressive clinical phases of liver disease to HCC. Several single and combinational mutations in HBx correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating the progression to HCC. These specific patterns of HBx mutations can be useful in predicting the clinical outcome of HBV-infected patients and may serve as early markers of high risk of developing HCC.

HBsAg clearance in chronic hepatitis B patients with add-on pegylated interferon alfa-2a to ongoing tenofovir treatment: A randomized controlled study.

BACKGROUND/AIMS: The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance. PATIENTS AND METHODS: In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups. One group (add-on therapy) was given subcutaneous PEG IFN 180 mcg weekly for 12 months in addition to tenofovir. Patients in the other group received only tenofovir 300 mg orally on a daily basis. Patients in both groups were followed up for a total of two years, and patients in both groups were given tenofovir 300 mg daily indefinitely until they developed HBsAg clearance. RESULTS: Twenty-three patients were allocated to the PEG IFN and tenofovir (add-on therapy) group, and another 25 patients were recruited to the tenofovir monotherapy group. Before randomization, patients had received tenofovir for 1135 mean days (range203 to 1542 days). One patient (4.3%) in add-on therapy lost HBsAg and seroconverted. Within two years, mean HBsAg decreased significantly with add-on therapy (from 4753 IU/ml to 2402; P= 0.03); and it decreased from 5957 IU/ml to 4198; P= 0.09 in tenofovir monotherapy group. More patients in the add-on group developed serious side effects, with treatment discontinuation, and dose reductions (P = 0.3). CONCLUSION: PEG IFN and tenofovir add-on therapy was successful in achieving HBsAg clearance and seroconversion in 4.3% of the patients. Add-on therapy patients had a significant decrease in HBsAg levels in two years; and no significant decrease in HBsAg levels with the tenofovir monotherapy. With no significant HBsAg clearance, the utility of this combination regimen is questionable.

The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia.

The relatedness between viral variants sampled at different locations through time can provide information pertinent to public health that cannot readily be obtained through standard surveillance methods. Here, we use virus genetic data to identify the transmission dynamics that drive the hepatitis C virus subtypes 4a (HCV4a) and 4d (HCV4d) epidemics in Saudi Arabia. We use a comprehensive dataset of newly generated and publicly available sequence data to infer the HCV4a and HCV4d evolutionary histories in a Bayesian statistical framework. We also introduce a novel analytical method for an objective assessment of the migration intensity between locations. We find that international host mobility patterns dominate over within country spread in shaping the Saudi Arabia HCV4a epidemic, while this may be different for the HCV4d epidemic. This indicates that the subtypes 4a and 4d burden can be most effectively reduced by combining the prioritized screening and treatment of Egyptian immigrants with domestic prevention campaigns. Our results highlight that the joint investigation of evolutionary and epidemiological processes can provide valuable public health information, even in the absence of extensive metadata information.

PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.

 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.

Clinical, endoscopic, and radiologic features of three subtypes of achalasia, classified using high-resolution manometry.

BACKGROUND/AIMS: High-resolution manometry (HRM) has improved the accuracy of manometry in detecting achalasia and determining its subtypes. However, the correlation of achalasia subtypes with clinical, endoscopic, and radiologic findings has not been assessed. We aimed to evaluate and compare the clinical, endoscopic, and fluoroscopy findings associated with three subtypes of achalasia using HRM. PATIENTS AND METHODS: The retrospective clinical data, HRM, endoscopy, and radiologic findings were obtained from the medical records of untreated achalasia patients. RESULTS: From 2011 to 2013, 374 patients underwent HRM. Fifty-two patients (14%) were diagnosed with achalasia, but only 32 (8.5%) of these patients had not received treatment and were therefore included in this study. The endoscopy results were normal in 28% of the patients, and a barium swallow was inconclusive in 31% of the achalasia patients. Ten patients (31%) were classified as having type I achalasia, 17 (53%) were classified as type II, and 5 (16%) were classified as type III. Among the three subtypes, type I patients were on average the youngest and had the longest history of dysphagia, mildest chest pain, most significant weight loss, and most dilated esophagus with residual food. Chest pain was most common in type III patients, and frequently had normal fluoroscopic and endoscopic results. CONCLUSION: The clinical, radiologic, and endoscopic findings were not significantly different between patients with type I and type II untreated achalasia. Type III patients had the most severe symptoms and were the most difficult to diagnose based on varied clinical, radiologic, and endoscopic findings.

Correlation between genetic variations and serum level of interleukin 28B with virus genotypes and disease progression in chronic hepatitis C virus infection.

Recent studies have demonstrated that polymorphisms near the interleukin-28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B serum level was detected and variations at five single nucleotide polymorphisms (SNPs) in IL28B gene region were genotyped and analyzed. The variation of IL28B genetic polymorphisms was found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all P values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (P = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P = 0.005 and 0.003, resp.). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. This study indicates that variation at SNP rs8099917 could predict the serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level may serve as a useful marker for the development of HCV-associated sequelae.

Diagnostic Utility of Impedance-pH Monitoring in Refractory Non-erosive Reflux Disease.

BACKGROUND/AIMS: Approximately one-third of non-erosive reflux disease (NERD) patients are refractory to proton pump inhibitors (PPI) and face a therapeutic challenge. Therefore, it is important to differentiate between pathological and non-pathological reflux utilizing multichannel intraluminal impedance-pH (MII-pH) to analyze symptom-reflux association and diagnose true NERD versus hyper-sensitive esophagus (HE) and functional heartburn (FH). Herein, we evaluated the diagnostic yield of MII-pH in refractory NERD and sub-classified it based on quantity and quality of acid/non-acid reflux and reflux-symptom association. METHODS: Sixty symptomatic NERD patients on twice daily PPI for > 2 months were prospectively evaluated by MII-pH. Distal and prox-imal refluxes, bolus exposure time (BET), esophageal acid exposure time, symptom index (SI) and symptom association proba-bility (SAP) were measured. RESULTS: Thirty-two (53%) patients had BET > 1.4% (MII-pH positive-true NERD), while 28 (47%) had BET < 1.4% (MII-pH negative NERD) where SI and SAP were negative in 15/60 (25%; categorized as FH) and SI or SAP were positive in 13/60 (22%; identi-fied as HE). Thirty-eight (63%) patients reported significant SI or SAP parameters where > 80% of symptoms were associated with non-acid reflux. The number of distal refluxes in true NERD versus FH or HE were significantly different, but not between FH and HE. CONCLUSIONS: Approximately 60% of refractory PPI NERD patients had positive reflux-symptom association, primarily due to non-acid reflux. Nearly half of NERD patients on PPI had normal MII-pH monitoring, sub-divided further into FH and HE equally.(J Neurogastroenterol Motil 2014;20:497-505).

The association of toll-like receptor 4 polymorphism with hepatitis C virus infection in Saudi Arabian patients.

Hepatitis C virus (HCV) is a single stranded RNA virus. It affects millions of people worldwide and is considered as a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians. This study aims to investigate the implication of genetic polymorphisms of TLR4 gene on the HCV infection in Saudi Arabian patients. Two SNPs in the TLR4 gene, rs4986790 (A/G) and rs4986791 (C/T), were genotyped in 450 HCV patients and 600 uninfected controls. The association analysis confirmed that both SNPs showed a significant difference in their distribution between HCV-infected patients and uninfected control subjects (P < 0.0001; OR = 0.404, 95% CI = 0.281-0.581) and (P < 0.0001; OR = 0.298, 95% CI = 0.201-0.443), respectively. More importantly, haplotype analysis revealed that four haplotypes, AC, GT, GC, and AT (rs4986790, rs4986791), were significantly associated with HCV infection when compared with control subjects. One haplotype AC was more prominently found when chronic HCV-infected patients were compared with cirrhosis/HCC patients (frequency = 94.7% and P = 0.04). Both TLR4 SNPs under investigation were found to be significantly implicated with HCV-infection among Saudi Arabian population.

Variations in DEPDC5 gene and its association with chronic hepatitis C virus infection in Saudi Arabia.

BACKGROUND: Variations at DEPDC5 gene have been recently reported as genetic markers associated with hepatocellular carcinoma (HCC) progression in chronic HCV-infected patients. This study was conducted to assess the association of DEPDC5 variants with advanced liver cirrhosis and HCC development among chronic HCV-infected patients in Saudi Arabian population. METHODS: Six-hundred and one HCV-infected patients were genotyped for DEPDC5 polymorphisms (rs1012068 and rs5998152), in comparison with 592 non-infected healthy control subjects. The allelic frequency and genotype distribution of both DEPDC5 polymorphisms were determined followed by haplotype frequency estimation and multiple logistic regression analysis. RESULTS: The frequency of the risk alleles of both rs1012068 and rs5998152 was shown to be more in healthy control subjects than in patients (p = 0.0001, OR = 0.704, CI = 0.591-0.839; p = 0.002, OR = 0.761, CI = 0. 0.639-0.907, respectively). Also, our results revealed that GT for SNP rs1012068 (OR =1.715; 95% CI 1.132-2.597; p = 0.0104) and CT for SNP rs5998152 (OR = 1.932; 95% CI 1.276-2.925; p = 0.0017) showed significant association with development of cirrhosis compared with the GG and CC genotypes, respectively. The data also revealed that subjects with the T allele of both SNPs appeared to have a lower susceptibility to HCV-related cirrhosis/HCC than those with the G allele of rs1012068 (p = 0.038, OR = 1.353, 95 % CI 1.017-1.800) and C allele of rs5998152 (p = 0.043, OR = 1.342, 95 % CI 1.010-1.784). Haplotype analysis showed that a combination of T-T alleles of rs1012068 and rs5998152 was significantly associated with liver cirrhosis (frequency = 71.3% and p = 0.027) and with cirrhosis/HCC (frequency = 71.4% and P = 0.045). Also, multiple logistic regression analysis showed that rs5998152 (OR = 2.844, 95% CI 1.333-6.069 and p = 0.007), rs1012068 (OR = 2.793, 95% CI 1.316-5.928 and p = 0.010), age (OR = 1.029, 95% CI 1.001-1.057 and p = 0.041) and HCV genotypes (OR = 0.247, 95% CI 0.097-0.630 and p = 0.003) were independently associated with chronicity of HCV infection. CONCLUSION: Genetic variations in DEPDC5 gene region may influence HCV-associated liver cirrhosis and/or HCC development.

Lung transplantation triggered "jackhammer esophagus": a case report and review of literature.

A 19-years-old girl was referred for lung transplant due to end stage lung disease secondary to idiopathic bilateral bronchiectasis. Her routine pre lung transplant evaluation showed normal esophageal high-resolution manometry (HRM) and 24-hours impedance pH monitoring. Four weeks after the bilateral sequential lung transplantation (LTx), she developed dysphagia, chest pain and regurgitation, complicated by aspiration pneumonia. Repeated HRM showed Jackhammer esophagus, delayed gastric emptying and abnormal 24-hour pH impedance monitoring consistent with the diagnosis of gastroesophageal reflux disease. Twelve weeks after LTx, she was symptom free, HRM and 24-hour impedance pH monitoring returned to normal. To the best of our knowledge, this rare transient esophageal hypercontractility episode occurred after LTx and recovered without any specific treatment was never reported in literature. The etiopathogenesis of Jackhammer esophagus in general and LTx induced dysmotility in particular is discussed and reviewed.

Relationship of interferon-γ-inducible protein-10 kDa with viral response in patients with various heterogeneities of hepatitis C virus genotype-4.

INTRODUCTION: The role of serum interferon-γ-inducible protein-10 kDa (IP-10) level in the treatment of chronic hepatitis C genotype-4 (HCV-4) and its various subtypes remains unknown. We aimed to study the impact of pretreatment IP-10 levels on the sustained viral response (SVR) in HCV-4 patients (n=64) undergoing peginterferon α-2a/ribavirin therapy. PATIENTS AND METHODS: Pretreatment IP-10 levels and HCV-4 subtypes (4a=48.4%, 4d=39%, others=12.5%) were measured and correlated with treatment responses. Variables significantly associated with SVR on univariate analysis were included in a multivariate logistic regression model. RESULTS: Patients with SVR had lower pretreatment IP-10 levels (462.4±282.7 vs. 840.1±490.6 pg/ml; P=0.002), but the levels were not significantly different in those with a rapid (P=0.245) or an early viral response (P=0.221). IP-10 levels were similar across all subtypes. The pretreatment level was significantly lower in subtype 4d patients with SVR (465.9±349.1) compared with non-SVR patients (904.9±532.1; P<0.001), but not when compared with genotype 4a patients (564.7±288.9 vs. 658.6±374.9, respectively; P=0.330). IP-10 levels [odds ratio (OR), 0.998; 95% confidence interval (CI): 0.996-0.999; P=0.006], low viremia (OR, 8.852; 95% CI: 1.244-63.03; P=0.029), and early viral response (OR, 4.162; 95% CI: 1.023-16.94; P=0.046) were independent predictors of SVR. Receiver operating characteristic curve analysis identified a threshold IP-10 level of 359 pg/ml (area under receiver operating characteristic curve, 0.737; sensitivity, 81.8%; specificity, 45.2; positive predictive value, 43.9%; negative predictive value, 82.6%) for SVR. CONCLUSION: Pretreatment serum IP-10 level is a predictor for SVR in HCV-4-infected patients. The baseline IP-10 level is significantly lower in responders among HCV genotype-4d patients as compared with 4a patients.

Hepatitis C genotype 4: genotypic diversity, epidemiological profile, and clinical relevance of subtypes in Saudi Arabia.

BACKGROUND/AIM: Hepatitis C virus genotypes 4 (HCV-4) is the most prevalent genotype in Saudi Arabia, although it's various subtypes, mode and route of transmission remains unknown. The aim of this study was to analyze (i) the variability of the HCV-4 subtypes, the route and source of HCV transmission and (ii) the influence of HCV-4 subtypes on their therapeutic response. PATIENTS AND METHODS: Sixty-four HCV-4 patients were analyzed retrospectively for the prevalence of various sub-genotypes and the possible mode of transmission, and it was correlated with their treatment response to pegylated interferon (PEG-IFN) α-2a and ribavirin therapy. RESULTS: Positive history of blood or blood products transfusion was noted in 22 patients (34%), hemodialysis in 10 patients (15.6%), surgery in 7 patients (11%), and unknown etiology in 25 patients (39%). Prevalence of HCV-4 subtypes was 4a = 48.4% (31/64), 4d = 39% (25/64), 4n = 6.25% (4/64), and remaining combined (4m, 4l, 4r, 4o) 6.25% (4/64). No significant correlation between subtypes and the source of transmission was recognized ( P = 0.62). Sustained virological response in all HCV-4 patients was 64% (41/64), while in each subtypes separately it was 4a 77.4% (24/31), 4d 52% (13/25), and combined (4n, 4m, 4l, 4r, 4o) 62.5% (5/8) ( P = 0.046). CONCLUSION: No obvious cause for the mode of HCV transmission was noted in majority of the patients. No significant correlation was observed between HCV-4 subtypes and the source of HCV infection. 4a and 4d subtypes were the most common in Saudi Arabia, and patients infected with 4a subtype responded significantly better to combination therapy than to 4d subtype.

Efficacy of peginterferon α-2a and predictors of response in HBeAg-negative, genotype D-naive patients.

BACKGROUND: Peginterferon (PEG-IFN) α-2a has been shown to induce a sustained virologic response (SVR) in 20-30% of "hepatitis B e antigen (HBeAg)"-negative patients. AIM: To determine the safety and efficacy of PEG-IFN α-2a in HBeAg-negative, genotype D-naive patients and to analyze the predictors of response. METHODS: This prospective, multicenter, open-label, nonrandomized trial was conducted at four hospitals. A total of 35 consecutive HBeAg-negative naive genotype D patients received PEG-IFN α-2a for 48 weeks. RESULTS: Based on a cutoff of hepatitis B virus (HBV) DNA <400 copies ml(-1), an early virologic response (EVR) at week 12, end of treatment virologic response (ETVR) at week 48, and SVR at week 72 were achieved by 3 (9%), 9 (26%), and 8 patients (23%), respectively. The EVR rate improved to 43%, ETVR to 49%, and SVR to 57%, when a HBV DNA cutoff level of <20,000 copies ml(-1) was used. Pretreatment HBsAg level was not a predictor for SVR on univariate analysis, but correlated with decline in HBV DNA levels at weeks 48 and 72. On multivariate logistic regression analysis, low body weight, high alanine aminotransferase (ALT), low HBV DNA, and low triglyceride levels were identified as baseline predictors of SVR. CONCLUSION: HBeAg-negative genotype D-naive patients treated with PEG-IFN α-2a achieved SVR in 23 (HBV <400 copies ml(-1)) and 57% (HBV <20,000 copies ml(-1)) of patients, a better response than previously reported that might be related to the absence of drug resistance in these naive patients. Pretreatment predictors of SVR were low body weight, high ALT, low HBV DNA, and low triglycerides.

Sustained virologic response to peginterferon alpha-2a and ribavirin in 335 patients with chronic hepatitis C: a tertiary care center experience.

BACKGROUND/AIM: This retrospective study assessed the efficacy, safety, and the predictors of sustained viral response (SVR) to a 48-week-course of peginterferon alpha-2a (Pegasys) and ribavirin combination therapy in 335 consecutive Saudi patients with chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS: Clinical, biochemical, and virological parameters were collected at time 0 (pretreatment) and at 12, 24, 48, and 72 weeks posttreatment. The mean +/- SD age was 49.1 +/- 13.0 years; 229 (68.4%) were males, mean +/- SD body mass index was 27.8 +/- 7.4, 85 (25.4%) were diabetic, 25 (7.5%) had renal impairment, 136 (40.6%) had previously received interferon +/- ribavirin therapy, and 247 (73.7%) underwent pretreatment liver biopsy. Patients with genotypes 1, 2 or 3, 4 and mixed genotype were 60 (22.15%), 30 (11.0%), 148 (54.4%), and 34 (12.5%), respectively. RESULTS: Early viral response (>or=2-log10 HCV-RNA decline 12 weeks posttreatment) was achieved in 253 (75.3%). Patients who completed 48 weeks of treatment were 292 (87.1%); of these, 121 (75.6%) achieved ETVR, 161 (55.1%) continued to have SVR and 60 (20.5%) had a viral relapse following end-of-treatment response, that is 48.1 and 17.9% of all patients (n = 335), respectively. Nonresponders (NR) were 71 (24.3%) patients and 43 (12.8%) were unable to complete treatment (due to side effects or loss to follow up). Compared to the relapsers, patients with SVR were significantly younger (P = 0.000), nondiabetics (P = 0.015), had higher serum albumin (P = 0.007), had less pretreatment inflammatory grade (P = 0.011), infected with genotypes 2 or 3 (P = 0.014), and treatment-naïve patients (P = 0.001). However, in stepwise multivariate logistic regression analysis, only treatment naiveté and low pretreatment inflammatory score were the independent predictors of SVR (P = 0.005 and P = 0.018, respectively). CONCLUSION: Combination therapy, if tolerated and completed, is effective in treating chronic HCV patients, especially those with no previous interferon therapy and lower pretreatment inflammatory grade.

Gastrosplenic fistula in Hodgkin's lymphoma treated successfully by laparoscopic surgery and chemotherapy.

A gastrosplenic fistula is a rare complication of a gastric or splenic lesion. We report a case of Hodgkin's lymphoma nodular sclerosis involving the spleen that was complicated by spontaneous gastrosplenic fistula. The fistula was closed laparoscopically, and the patient underwent partial gastrectomy and gastric wall repair, followed by successful chemotherapy. This is also the first reported case in published literature where closure of gastrosplenic fistula and partial gastrectomy was carried out laparoscopically. We recommend that extensive open surgical procedures including total gastrectomy, splenectomy, and pancreatectomy may be avoided in the management of gastrosplenic fistula, and the patient could be managed by less radical, simple laparoscopic fistulectomy, with partial gastric resection. If the fistula is caused by a malignant process, the surgical repair should be followed by definitive treatment with chemotherapy and radiotherapy.