HCV and cancer: a case-control study in a high-endemic area

BACKGROUND/AIMS: HCV is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenic potential indirectly by contributing to the modulatory effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case-controlled study on the different oncological pathologies which have, to date, been shown to have a relationship with HCV. METHODS: We screened 495 patients with different types of cancer: 114 cases of liver cancer, 41 of multiple myeloma, 111 non-Hodgkin's lymphomas, 130 thyroid cancers, 63 cases of Hodgkin's disease. The controls were 226 patients with no history of cancer. The relationship between each cancer and HCV infection was assessed by means of odds ratios (OR) and corresponding 95% confidence intervals. RESULTS: Risks were greater for liver cancer (OR=32.9 95% CI 16.5-65.4, p<0.0001), multiple myeloma (OR=4.5 95% CI 1.9-10.7, p=0.0004) and B-cell non-Hodgkin's lymphoma (OR=3.7 95% CI 1.9-7.4, p=0.0001). For Hodgkin's disease there was no significant association (p=0.3). An association between HCV and thyroid cancer was noted (OR=2.8 95% CI 1.2-6.3, p=0.01). CONCLUSION: Our study is particularly important for public health since the high prevalence of HCV in the South of Italy gives reason to expect increases in not only liver cancer, but also tumors associated with the immune system and thyroid cancer in years to come.     

Correlates of high hepatitis C virus RNA load in a cohort of HIV‐negative and HIV‐positive individuals with haemophilia

Summary. Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV‐RNA load. Correlates of high HCV‐RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV‐infected individuals with haemophilia, we compared those with high (>2 × 10⁶ HCV‐RNA copies/mL) to lower viral load, overall and stratifying on HIV co‐infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P_trend = 0.0001), body mass index ≥25 kg/m² (OR = 1.4, 95% CI = 1.1–1.9), and HIV co‐infection (OR = 1.4, 95% CI = 1.0–1.8). Among 795 HIV‐negative participants, high HCV‐RNA load was associated with older age at HCV acquisition (OR = 1.9 for >15 years vs≤2 years, P_trend = 0.008), and lower AST/platelet ratio (P_trend = 0.01), in addition to longer duration of HCV infection (P_trend = 0.0008), and body mass index ≥25 kg/m² (OR = 1.6, P = 0.005). Among 471 HIV‐positive individuals, anti‐retroviral therapy (ART) was the only variable associated with high HCV‐RNA load (OR = 1.8, CI = 1.1–2.9 for combination ART; OR = 1.8, CI = 0.9–3.4, for other ART vs no treatment). High HCV‐RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end‐stage liver disease.     

Significant association between toll‐like receptor gene polymorphisms and gallbladder cancer

Background: Toll‐like receptors (TLRs) are evolutionarily conserved cell surface receptors of innate immune system. Various polymorphisms in TLR genes have been identified and associated with susceptibility toward various malignancies such as prostate cancer, gastric cancer and colorectal cancer. The present study was undertaken to examine the potential association of two polymorphisms in TLR2 and TLR4 genes with gallbladder cancer (GBC) susceptibility. Methods: Genotypes and allelic frequencies of TLR2 and TLR4 gene polymorphisms were determined for 233 GBC patients and 257 cancer‐free controls randomly selected from the population, using polymerase chain reaction–restriction fragment length polymorphism. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in a multivariate logistic regression analysis for the association of TLR polymorphisms with GBC. Results: ‘del’ allele carriers of TLR2 (Δ22) polymorphism were associated with a 1.54‐fold increased risk for GBC (95% CI=1.02–2.24; P_trend=0.091). The TLR4 Ex4+936C >T polymorphism (g.14143C>T; rs4986791) was also found to be significantly associated with the overall higher risk of GBC under a dominant mode of inheritance (OR=1.96; 95% CI=1.11–2.26; P_trend=0.021). The false‐positive report probability (FPRP) approach advocated that these results were noteworthy (FPRP<0.5). Subgroup analysis showed that TLR4 Ex4+936C>T polymorphism was associated with an increased risk of GBC in females and GBC cases with gallstones (OR=2.85 and 2.22 respectively). Conclusion: In summary, low‐penetrance variants in TLR genes may alter the susceptibility towards gallbladder cancer.     

Relationship between IL‐10 gene −1082A/G and −592C/A polymorphisms and the risk of hepatitis C infection: a meta‐analysis

Increasing evidence suggests that interleukin‐10 (IL‐10) gene promoter polymorphisms may be associated with chronic hepatitis C virus (HCV) infection and HCV clearance. To more precisely estimate the association between these variants and the risk of HCV infection, we performed a meta‐analysis of 26 studies describing the IL‐10–1082A/G, –819C/T, –592C/A genotypes, including 4039 chronic HCV infection cases and 2902 controls. When compared with a healthy population, the –1082GG allele had a 43% increased risk of chronic HCV infection in combined populations (GG vs GA + AA: odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.052–1.952, P = 0.023). In subgroup analysis by ethnicity, a significant increased risk was associated with the ?1082GG genotype in the Caucasian population (GG vs AA: OR = 1.390, 95% CI: 1.108–1.744, P = 0.004; GG vs GA + AA: OR = 1.621, 95% CI: 1.267–2.075, P = 0.000). However, no significant association was found in Asian, African or Chinese populations. Moreover, a higher distribution of ?592A was found in the spontaneously recovered population (AA vs CC: OR = 0.585, 95% CI = 0.387–0.884, P = 0.011; AA + AC vs CC: OR = 0.738, 95% CI = 0.551–0.988, P = 0.041; AA vs AC + CC: OR = 0.788, 95% CI = 0.664–0.935, P = 0.006) than that in the chronic HCV infection population. In conclusion, the IL‐10–1082GG allele may increase the risk of chronic HCV infection in Caucasian population, and people carrying the IL‐10–592A allele are more likely to clear HCV spontaneously.     

Meta‐analysis of alcohol consumption and risk of extrahepatic bile system cancer

Aim: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta‐analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. Methods: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). Results: A total of 113 767 participants from 10 studies (nine case–control studies and one cohort study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for drinkers versus non‐/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72–0.94, P for heterogeneity = 0.194, I² = 27.2%). The overall adjusted OR of hospital‐based studies and population‐based studies were 0.80 (95% CI = 0.65–0.99, P = 0.260) and 0.79 (95% CI = 0.64–0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97–2.57, P for heterogeneity = 0.055, I² = 65.4%), but it had no statistical significance. Conclusion: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non‐/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.     

Association of IFNL3 and IFNL4 polymorphisms with liver‐related mortality in a multiracial cohort of HIV/HCV‐coinfected women

African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver‐related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV‐related outcomes, the impact of these variants on liver‐related mortality has not been investigated. We conducted a cohort study of HIV/HCV‐coinfected women followed in the multicentre, NIH‐funded Women's Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN‐λ region were associated with liver‐related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver‐related death by race/ethnicity (ascertained by self‐report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver‐related deaths during up to 18 years of follow‐up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14–0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45–0.99, P = 0.047) were most strongly associated with liver‐related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16–1.04, P = 0.060 and HR 0.78, 95% CI 0.51–1.19, P = 0.25, respectively). African American women had persistently lower liver‐related death independent of IFN‐λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV‐coinfected women is not explained by genetic variation in the IFN‐λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver‐related mortality.     

Impact of hepatitis C virus infection on all‐cause and liver‐related mortality in a large community‐based cohort of inner city residents

Summary. The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community‐based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause‐specific mortality rates and factors associated with all‐cause and liver‐related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non‐injection drug use – 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10 000 person‐years; 95% CI: 165, 222), with 21% HIV‐related, 20% drug‐related and 7% liver‐related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs <40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver‐related mortality was associated with age >50 [AHR 18.49 vs <40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV‐infected inner city residents >50 years of age were at significant risk of liver‐related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.     

Hepatitis C virus infection and risk of multiple myeloma: Evidence from a meta‐analysis based on 17 case‐control studies

Hepatitis C virus (HCV) infection is a leading cause of chronic liver damage and is associated with other diseases. Some studies reported that patients with HCV have a significantly increased risk of multiple myeloma while others do not report an association. We aimed to clarify the association between HCV and multiple myeloma and analyse the factors that affect the controversial conclusions through a meta‐analysis. We conducted a systematic literature search of HCV and myeloma in the databases of PubMed/MEDLINE, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure (CNKI) from inception to September 2016. Outcomes were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). A positive correlation between HCV infection and risk of developing multiple myeloma was revealed (OR=2.67, 95% CI=1.35‐5.26, P=.005) based on meta‐analysis of 17 case‐control observational studies. When the data were stratified by source of control, significant associations were observed in hospital‐based studies, but not population‐based studies. Further subgroup analyses showed increased risk of multiple myeloma in HCV patients when studies were conducted in high HCV prevalent countries, but not in low or moderate HCV prevalent countries. In addition, similar positive association was detected in studies performed in the East Asia and in intermediate‐quality studies. In summary, the association of HCV infection with increased risk of multiple myeloma depended on several factors, including study design, quality and environmental HCV prevalence. Further large‐scale, well‐designed studies are needed to validate the role of HCV in the aetiology of multiple myeloma.     

Factors associated with the presence of multiple Lugol‐voiding lesions in patients with esophageal squamous‐cell carcinoma

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol‐voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence‐specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84–122.45: P = 0.011), presence of the ALDH2‐2 allele (OR 4.5, 95% CI 1.55–13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02–6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13–88.44: P = 0.038) and presence of the ALDH2‐2 allele (OR 4.56, 95% CI 1.4–14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2‐2 allele (OR 17.5, 95% CI 1.97–155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2‐2 allele (OR 8.85, 95% CI 1.68–46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2‐2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2‐2 allele (OR 4.0, 95% CI 0.54–29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2‐2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2‐2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.     

Role of epoxide hydrolase 1 gene polymorphisms in esophageal cancer in a high‐risk area in India

Background and Aim: Microsomal epoxide hydrolase 1 (EPHX1) is involved in the metabolism of environmental and tobacco carcinogens. Tobacco smoking, betel quid chewing, and alcohol consumption are the major known risk factors for esophageal cancer. The present case‐control study evaluated the influence of EPHX1 genetic variations on esophageal cancer susceptibility in 142 patients and 185 healthy controls from a high‐incidence region of India where tobacco use and alcohol consumption are widespread and the users of these two substances are also betel quid chewers. Methods: EPHX1 polymorphic alleles (exon 3, Tyr113His and exon 4, His139Arg) were genotyped by polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing. The results were analyzed using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). Results: Patients with exon 4 genotypes (139His/Arg, 139Arg/Arg) and the 139Arg allele were significantly associated with a risk of esophageal cancer (OR_His139Arg 1.887, 95% CI = 1.112–3.201, P = 0.019; OR_Arg139Arg 7.140, 95% CI = 1.276–393.953, P = 0.025 and OR_Arg 1.83, 95% CI = 1.19–2.82, P = 0.003). The 139His/Arg genotype was a significant risk factor for esophageal cancer in tobacco chewers and betel quid chewers. Patients with the 139Arg/Arg genotype were at significantly higher risk for developing a well‐differentiated and moderately‐differentiated grade of tumor. In contrast, the 113His/His genotype of exon 3 was a significant protective factor for esophageal cancer in tobacco smokers (OR 0.291, 95% CI = 0.138–0.616, P = 0.001), betel quid chewers (OR 0.434, 95% CI = 0.236–0.797, P = 0.007), and alcohol users. Conclusion: EPHX1 exon 4 139His/Arg, and 139Arg/Arg genotypes were associated with a higher risk of esophageal cancer in a high‐risk area of India.     

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: An updated meta‐analysis of case–control studies

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta‐analyses have reported inconclusive results. Therefore, an updated meta‐analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant ‘null’ genotype was compared with wild‐type ‘present’ in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case–control studies were suitable for inclusion in the meta‐analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192–1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293–2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051–1.781) and adults (OR = 1.859; 95% CI: 1.183–2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204–4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018–1.667), Africa (OR = 2.175; 95%CI: 1.560–3.031) and Latin America (OR = 2.265; 95%CI: 1.375–3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101–4.025) and Russian (OR = 2.747; 95% CI: 1.071–7.046) populations. This meta‐analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.     

Polymorphisms of drug‐metabolizing genes and risk of non‐Hodgkin lymphoma

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug‐metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non‐Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population‐based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)_AG = 0.67, 95% confidence interval (CI) = 0.55–0.82; OR_AG/GG = 0.66, 95% CI = 0.54–0.80) and DLBCL (OR_AG = 0.63, 95% CI = 0.49–0.82; OR_AG/GG = 0.64, 95% CI = 0.50–0.82). For T‐cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR_AG/GG = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR_AG = 1.28, 95% CI = 1.07–1.54; OR_AG/GG = 1.26, 95% CI = 1.06–1.51) and DLBCL (OR_AG = 1.32, 95% CI = 1.04–1.66; OR_AG/GG = 1.30, 95% CI = 1.03–1.63), but not T‐cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

The anti‐lymphoma activity of antiviral therapy in HCV‐associated B‐cell non‐Hodgkin lymphomas: a meta‐analysis

Many epidemiological studies provide solid evidence for an association of chronic hepatitis C virus (HCV) infection with B‐cell non‐Hodgkin's lymphoma (B‐NHL). However, the most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B‐NHL regression after HCV eradication by antiviral therapy (AVT). We conducted a literature search to identify studies that included patients with HCV‐associated B‐NHL (HCV‐NHL) who received AVT, with the intention to treat lymphoma and viral disease at the same time. The primary end point was the correlation of sustained virological response (SVR) under AVT with lymphoma response. Secondary end points were overall lymphoma response rates and HCV‐NHL response in correlation with lymphoma subtypes. We included 20 studies that evaluated the efficacy of AVT in HCV‐NHL (n = 254 patients). Overall lymphoma response rate through AVT was 73% [95%>confidence interval, (CI) 67–78%]. Throughout studies there was a strong association between SVR and lymphoma response (83% response rate, 95%>CI, 76–88%) compared to a failure in achieving SVR (53% response rate, 95%>CI, 39–67%, P = 0.0002). There was a trend towards favourable response for AVT in HCV‐associated marginal zone lymphomas (response rate 81%, 95%>CI, 74–87%) compared to nonmarginal zone origin (response rate 71%, 95%>CI, 61–79%, P = 0.07). In conclusion, in the current meta‐analysis, the overall response rate of HCV‐NHL under AVT justifies the recommendation for AVT as first‐line treatment in patients who do not need immediate conventional treatment. The strong correlation of SVR and lymphoma regression supports the hypothesis of a causal relationship of HCV and lymphomagenesis.     

A meta‐analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection

Epidemiological studies have reported conflicting results regarding hepatitis C virus (HCV) infection and the risk of chronic kidney disease (CKD). We systematically reviewed the literature to determine the risk of developing CKD in HCV‐infected individuals compared to uninfected individuals. MEDLINE and PUBMED were searched to identify observational studies that had reported an association between HCV and CKD or end‐stage renal disease (ESRD) through January 2015. Quantitative estimates [hazard ratio (HR) or odds ratio (OR)] and their 95% confidence intervals (CI) were extracted from each study. A random‐effects meta‐analysis was performed. Fourteen studies evaluating the risk of developing CKD/ESRD in HCV‐infected individuals (n = 336 227) compared to uninfected controls (n = 2 665 631) were identified‐ nine cohort studies and five cross‐sectional studies. The summary estimate indicated that individuals with HCV had a 23% greater risk of presenting with CKD compared to uninfected individuals (risk ratio = 1.23; 95% CI: 1.12–1.34). Results were similar by study type, for cohorts (HR = 1.26; 95% CI: 1.12–1.40) and cross‐sectional studies (OR = 1.21; 95% CI: 1.09–1.32). Country‐stratified analysis demonstrated a significantly increased risk between HCV and CKD in the Taiwanese subgroup (risk ratio = 1.28; 95% CI: 1.12–1.34) and the US subgroup (risk ratio = 1.17; 95% CI: 1.01–1.32). Egger regression revealed no evidence of publication bias. HCV infection is associated with a greater risk of developing and progression of CKD compared to uninfected controls.     

Similar recovery of liver function after response to all‐oral HCV therapy in patients with cirrhosis with and without HIV coinfection

Among patients with cirrhosis, recovery of liver function after SVR to all‐oral direct‐acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV‐monoinfected and HIV/HCV‐coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR‐DAA and GEHEP‐MONO cohorts were selected if they had SVR12 to all‐oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child‐Pugh‐Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV‐infected individuals and in 82 (57%) HIV/HCV‐coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV‐monoinfected patients and in 33 (13%) HIV/HCV‐coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03‐4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004‐3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2‐5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3‐12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV‐monoinfected and HIV/HCV‐coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.     

Cryptogenic pyogenic liver abscess as a sign of colorectal cancer: a population‐based 5‐year follow‐up study

Background/aims: No large‐scale population‐based study has ever been conducted to examine the relationship between cryptogenic pyogenic liver abscesses (PLA) and the subsequent risk of colorectal cancer. This study aimed to estimate the risk for colorectal cancer following a diagnosis of cryptogenic PLA over a 5‐year period. Methods: The study group comprised 274 patients who visited an outpatient care centre or were hospitalized with a diagnosis of cryptogenic PLA between 2001 and 2003. The comparison group included 1370 randomly selected subjects. Cox proportional hazard regressions were performed to compare the 5‐year colorectal cancer‐free survival rates for these two groups. Results: Of the total sample, 40 patients from the study group (2.43%) had colorectal cancer during the 5‐year follow‐up period: 15 (5.45% of those with cryptogenic PLA) and 25 from the comparison group (1.82% of the comparison group). After adjusting for patients' age, sex, monthly income, level of urbanization and geographical location, the hazard of colorectal cancer during the 5‐year period was 3.36 times greater for patients with cryptogenic PLA than for the comparison group [95% confidence interval (CI)=1.72–6.56, P<0.001]. The adjusted hazard of colorectal cancer during the 5‐year follow‐up period was 5.54 times higher for cryptogetic PLA patients with diabetes (95% CI=2.11–14.56, P<0.001) than the comparison group and 2.64 times higher among PLA patients without diabetes (95% CI=1.19–5.85, P<0.05). Conclusions: We conclude that cryptogenic PLA is an alarm that may signal colorectal cancer, especially among female patients with diabetes.     

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case‐control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case‐control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real‐time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85–1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02–2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92–1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15–2.74) for EC overall. In never‐smokers and ever‐smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37–0.95) and 1.39 (95% CI = 1.00–1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case‐control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.     

Current evidence on the relationship between murine double minute 2 T309G polymorphism and esophageal cancer susceptibility

The relationship between murine double minute 2 (MDM2) T309G polymorphism and esophageal cancer risk has been discussed with discrepant results. The aim of our study is to investigate the systematic association between the potentially functional MDM2 T309G polymorphism and esophageal cancer risk. Eligible studies were included through searching the databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (up to April 2014). The crude odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. Six published case–control studies, including 1899 cases and 3016 controls, were identified. Overall, our study suggested that MDM2 T309G polymorphism was significantly associated with increased risk of esophageal cancer (TT vs. GG: OR = 0.77, 95% CI = 0.65–0.90, P = 0.002; T vs. G: OR = 0.88, 95% CI = 0.81–0.96, P = 0.002). In subgroup analyses stratified by source of controls, ethnicity, and quality score assessment, respectively, similar results were obtained (TT vs. GG: OR = 0.65, 95% CI = 0.48–0.89, P = 0.007 for hospital‐based studies; T vs. G: OR = 0.90, 95% CI = 0.81–0.99, P = 0.04 for population‐based studies; and T vs. G: OR = 0.85, 95% CI = 0.78–0.93, P = 0.004 for Asians). The results of Begg's test and Egger's test did not suggest publication bias in the studies. Therefore, the MDM2 T309G polymorphism may be significantly associated with increased esophageal cancer risk, especially among Asians.     

Microsomal triglyceride transfer protein polymorphism (−493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

Background: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)‐related steatosis. The MTP ?493G/T polymorphism may promote liver fat accumulation, but its role in HCV‐related steatosis is still unclear. Methods: Two hundred ninety‐eight CHC patients were studied and genotyped for MTP ?493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup. Results: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV‐3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2–3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non‐3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22–3.86; P=0.008). Moreover, TT carriers had higher high‐density lipoprotein (65.6±14.6 vs 56.1±16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80±0.3 vs 1.60±0.3 g/L; P=0.005) levels than G allele carriers. Conclusions: Chronic hepatitis C patients with the MTP ?493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non‐3 patients.