Mortality In Chronic Hepatitis Research Articles

Association of Alcohol Consumption With Liver Cancer and All-Cause Mortality in Chronic Hepatitis B Patients Without Cirrhosis

Association of Alcohol Consumption With Liver Cancer and All-Cause Mortality in Chronic Hepatitis B Patients Without Cirrhosis

Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR.

Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.

A Novel Noninvasive Index for Assessment of Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis C Virus Infection

Background: Liver fibrosis and cirrhosis are major causes of morbidity and mortality in chronic hepatitis C (CHC) patients. Objective: To assess a novel non-invasive index in prediction of hepatic fibrosis and cirrhosis in chronic hepatitis c patients by using red cell distribution width to platelet ratio (RPR). Patients and Methods: This cross-sectional study was conducted on 84 patients with hepatitis C virus in El Ahrar Teaching Hospital during the period from May 2019 to October 2019. The patients were classified into 3 groups, group (I) 26 CHC cases without fibrosis, group (II) 48 CHC cases with fibrosis, and group (III) 10 CHC cases with cirrhosis. The patients were subjected to history taking, clinical examination, laboratory investigations (CBC, liver function, kidney function, INR), and imaging modalities. Results: There was a higher sensitivity of RPR (83.3%) in detecting fibrotic liver among CHC cases and ability of 73.4% to negative cases among truly negatives, with higher accuracy of 78.6% than other scores which had high sensitivity of 75%, 77.1% and 68.8% and specificity of 69.4%, 72.2% and 72.2% of APRI score, FIB4 and AAR respectively. While, there was a higher sensitivity of RPR (90%) in detecting cirrhotic liver among CHC cases and ability of 97.4% to detect negative cases among truly negatives, with higher accuracy of 96.4% than other scores, which had high sensitivity of 90%, 80% and 80% and specificity of 95.9%, 85.9% and 95.5% of APRI score, FIB4 and AAR respectively. Conclusion: The progression and prognosis of chronic hepatitis C using a complete blood cell count.

A Novel Noninvasive Index for Assessment of Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis C Virus Infection

Background: Liver fibrosis and cirrhosis are major causes of morbidity and mortality in chronic hepatitis C (CHC) patients. Objective: To assess a novel non-invasive index in prediction of hepatic fibrosis and cirrhosis in chronic hepatitis c patients by using red cell distribution width to platelet ratio (RPR). Patients and Methods: This cross-sectional study was conducted on 84 patients with hepatitis C virus in El Ahrar Teaching Hospital during the period from May 2019 to October 2019. The patients were classified into 3 groups, group (I) 26 CHC cases without fibrosis, group (II) 48 CHC cases with fibrosis, and group (III) 10 CHC cases with cirrhosis. The patients were subjected to history taking, clinical examination, laboratory investigations (CBC, liver function, kidney function, INR), and imaging modalities. Results: There was a higher sensitivity of RPR (83.3%) in detecting fibrotic liver among CHC cases and ability of 73.4% to negative cases among truly negatives, with higher accuracy of 78.6% than other scores which had high sensitivity of 75%, 77.1% and 68.8% and specificity of 69.4%, 72.2% and 72.2% of APRI score, FIB4 and AAR respectively. While, there was a higher sensitivity of RPR (90%) in detecting cirrhotic liver among CHC cases and ability of 97.4% to detect negative cases among truly negatives, with higher accuracy of 96.4% than other scores, which had high sensitivity of 90%, 80% and 80% and specificity of 95.9%, 85.9% and 95.5% of APRI score, FIB4 and AAR respectively. Conclusion: The progression and prognosis of chronic hepatitis C using a complete blood cell count.

Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs

To evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs). 773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden's index. Patients were grouped by pLSM: <10 kPa [reference], 10-17.4 kPa and ≥17.5 kPa. Primary outcomes were incident hepatocellular carcinoma and secondary outcomes were incident decompensated cirrhosis and all-cause mortality, analyzed using cox-regression. Median follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7-17.8, range 2.5-75) and pLSM of <10 kPa, 10-17.4 kPa and 17.5-75 kPa was seen in 41.5%, 32.2% and 26.3%. During a median follow-up time of 36 months, 11 (1.4%) developed HCC, 14 (1.5%) developed decompensated cirrhosis, and 38 (4.9%) patients died. A pLSM of 17.5 kPa identified patients with a high risk of HCC with a negative predictive value of 98.9% and incidence rate of HCC in the 17.5-75 kPa group of 1.40/100 person years compared to 0.14/100 person years and 0.12/100 person years in the 10-17.4 kPa and <10 kPa groups, p<0.001. Pretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter.

A comparative study of risks for hepatocellular carcinoma and mortality in chronic hepatitis B patients initially treated with entecavir or tenofovir

A comparative study of risks for hepatocellular carcinoma and mortality in chronic hepatitis B patients initially treated with entecavir or tenofovir

Nonalcoholic Steatohepatitis Is Associated With Liver-Related Outcomes and All-Cause Mortality in Chronic Hepatitis B.

Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease are increasingly observed together in clinical practice, and development of nonalcoholic steatohepatitis (NASH) represents another leading cause of liver-related morbidity and mortality. Our aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors. CHB patients attending two tertiary centers in North America and Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no-NASH or probable/definite NASH based on standardized histological assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan-Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events. There were 1,089 CHB patients, classified as no-NASH (n=904, 83%) or NASH (n=185, 17%), with 52 (6%) versus 27 (15%) experiencing outcome events during follow-up, respectively. In the multivariable analysis adjusting for age, sex, hepatitis B e antigen serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (hazard ratio [95% confidence interval], 4.8 [2.6-9.0], P<0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (P=0.01) or NASH alone (P<0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (P<0.05) in place of NASH. NASH was significantly associated with increased risk of hepatocellular carcinoma and death (P<0.01) but not decompensation (P=0.33). In our large combined tertiary center cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver-related outcomes or death compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population.

Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Prospective propensity score (PS)-matched cohort. Swedish registers, 2005 to 2013. A PS-matched cohort of 16668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63279 eligible adults. Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users. Lack of lipid, fibrosis, or HCC surveillance data. In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. None.

Sa1620 – Coincidental Nonalcoholic Steatohepatitis Increases the Risk of Liver-Related Complications and Overall Mortality in Chronic Hepatitis B Patients with Undetectable/Low Serum Hbv Dna Levels During Long-Term Antiviral Therapy

Sa1620 – Coincidental Nonalcoholic Steatohepatitis Increases the Risk of Liver-Related Complications and Overall Mortality in Chronic Hepatitis B Patients with Undetectable/Low Serum Hbv Dna Levels During Long-Term Antiviral Therapy

Population-based study of Entecavir and long-term mortality in chronic hepatitis B–related decompensated liver cirrhosis

We lack population-based studies that identify the role of entecavir (ETV) in extending long-term survival in chronic hepatitis B (CHB)-related decompensated liver cirrhotic patients. Since 2010, National Health Insurance in Taiwan has covered long-term medical payment for antiviral therapy in CHB-related cirrhotic patients whose HBV DNA is ≥ 2000 IU/mL. We studied the effect of ETV on the mortality of CHB-related decompensated cirrhosis patients compared with patients who did not receive antiviral agents at baseline. From the Taiwan National Health Insurance Database, we collected 758 CHB-related decompensated cirrhosis patients with elevated viral loads (HBV DNA ≥ 2000 IU/mL) using ETV and discharged between January 1, 2010, and December 31, 2013. The comparison group consisted of 1516 selected CHB-related decompensated cirrhotic patients without antiviral therapy at baseline using propensity score matching analysis. The 1-, 2-, and 3-year mortality probabilities were 34.7%, 42.5%, and 48.5 % in the ETV group and 21.1%, 37.8% and 51.3 % in the non-ETV group, respectively. Based on a Cox proportional hazards regression model adjusted by patients' sex, age, and comorbid disorders, the hazard ratios (HR) in the ETV group for 1-year, 1-2-year, and 2-3-year mortalities were 1.22 (95% confidence interval [CI] 1.05-1.43, P = .010), 1.02 (0.86-1.20, P = .866), and 0.59 (0.38-0.90, P = .016), compared with the non-ETV group. Even in CHB-related decompensated cirrhotic patients, higher initial viral loads were correlated with poor outcomes. However, the long-term usage of ETV can decrease long-term mortality in these patients.

Sustained virological response and metabolic risk factors are associated with mortality in patients with chronic hepatitis C.

Background and aimPrevious studies have reported that sustained virological response (SVR) to interferon-based treatment reduces the risk of mortality in chronic hepatitis C (CHC) patients, mainly in cirrhotic patients. A population-based study reported that metabolic risk factors increase the risk of mortality in CHC patients. We aim to investigate the association between SVR, metabolic risk factors and mortality in CHC patients with and without advanced fibrosis.MethodsWe collected data from 1452 CHC patients who underwent interferon-based therapy. All patients underwent liver biopsy prior to therapy. Mild fibrosis was defined as a modified Knodell score of 0–2, while advanced fibrosis was defined as a score of 3–4.Results1452 patients were followed up for a median (IQR) of 6.6 (4.2–9.4) years, 1124 patients (77.4%) achieved SVR, 619 patients (42.6%) were advanced fibrosis. 14 patients with mild fibrosis and 55 patients with advanced fibrosis died during follow-up period. According to multivariate Cox regression analyses, SVR reduced the risks of all-cause mortality (HR, 0.21; 95% CI, 0.12–0.37; P<0.001), liver-related mortality (HR, 0.19; 95% CI, 0.10–0.38; P < .001), and non-liver-related mortality (HR, 0.26; 95% CI, 0.10–0.71; P = 0.009) in the patients with advanced fibrosis. SVR also reduced the risk of liver-related mortality (HR, 0.09; 95% CI, 0.01–0.60; P = 0.013) in the patients with mild fibrosis. Anti-hypertensive treatment increased the risks of all-cause mortality (HR, 6.1; 95% CI: 1.66–22.54; P = 0.006) and liver-related mortality (HR, 12.3; 95% CI: 1.4–108.5; P = 0.02) in the patients with mild fibrosis.ConclusionSVR and metabolic risk factors are associated with mortality in CHC patients given interferon-based treatment.

Medication Nonadherence Increases Hepatocellular Carcinoma, Cirrhotic Complications, and Mortality in Chronic Hepatitis B Patients Treated With Entecavir.

Optimal adherence to nucleoside analogue treatment is necessary to achieve undetectable levels of hepatitis B virus (HBV) DNA in patients with chronic hepatitis B (CHB), and to prevent cirrhotic complications. However, any large long-term follow-up study has not been investigated the effect of adherence to entecavir (ETV) treatment on specific liver-related events (LREs), namely, hepatocellular carcinoma (HCC), cirrhotic complications, and mortality. This was a 10-year longitudinal observational study of treatment-naïve patients with CHB who received ETV treatment. The primary outcome was the cumulative probability of LREs. The cumulative level of adherence to medication was categorized as good (≥90%) or poor (<90%). Data from 894 treatment-naïve CHB patients who received ETV were analyzed. Overall mean adherence rates were 89.1%. Patients with poor adherence had a higher risk of virologic breakthrough (VBT) (HR, 22.42; 95% CI, 19.57-52.52; P < 0.001) than those with good adherence. Multivariate analyses showed a higher risk of liver-related (HR, 14.29; 95% CI, 3.49-58.47; P < 0.001) or all-cause (HR, 4.96; 95% CI, 2.19-11.27; P < 0.001) mortality, HCC (HR, 2.86; 95% CI, 1.76-4.64; P < 0.001), and cirrhotic complications (HR, 2.86; 95% CI, 1.93-4.25; P < 0.001) with poor adherence. Medication adherence was further stratified into three groups according to adherence rates of <70%, ≥70 to <90%, and ≥90%. The dose-response analyses of adherence rates showed that the risk of LREs increased progressively as medication adherence declined. In particular, the unfavorable effects of nonadherence were more pronounced in patients with cirrhosis. Poor adherence to medication was associated with a higher mortality and greater risk of HCC and cirrhotic complications, particularly among patients with liver cirrhosis.

Internal driving factors leading to extrahepatic manifestation of the hepatitisC virus infection.

The hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, which are correlated with poor outcomes, and thus increase the morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding the internal linkages between systemic manifestations and HCV infection is helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the systemic diseases remains to be elucidated. In the present study, using gene set enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a comprehensive analysis of micro-array data of mRNAs was conducted in HCV-infected and -uninfected Huh7.5 cells, and signaling pathways (which are significantly activated or inhibited) and certain molecules (which are commonly important in those signaling pathways) were selected. Forty signaling pathways were selected using GSEA, and eight signaling pathways were selected with SPIA. These pathways are associated with cancer, metabolism, environmental information processing and organismal systems, which provide important information for further clarifying the intrinsic associations between syndromes of HCV infection, of which seven pathways were not previously reported, including basal transcription factors, pathogenic Escherichia coli infection, shigellosis, gastric acid secretion, dorso-ventral axis formation, amoebiasis and cholinergic synapse. Ten genes, SOS1, RAF1, IFNA2, IFNG, MTHFR, IGF1, CALM3, UBE2B, TP53 and BMP7 whose expression may be the key internal driving molecules, were selected using the online tool Anni 2.1. Furthermore, the present study demonstrated the internal linkages between systemic manifestations and HCV infection, and presented the potential molecules that are key to those linkages.

Long Term Seroprotection after Hepatitis B vaccination

Hepatitis B infection is a global public health problem. Morbidity and mortality in chronic hepatitis B infection are linked to persistence of viral replication and evolution to end stage liver disease and hepatocellular carcinoma(HCC). Despite advances in antiviral therapy, only a minority of patients with chronic hepatitis B will have a sustained response to treatment. Thus, the primary prevention by vaccination remains the main plunge in the control of hepatitis B virus infection. Currently available hepatitis B vaccines are extremely safe and efficacious, effective against all HBV serotypes and genotypes. Seroprotection after HBV vaccination persists for years, protection from clinical disease despite declining anti-HBs levels is probably due to the priming of memory cells, which are capable of eliciting anamnestic response when challenged To date there are no data to support the need for booster dose in immunocompetent individuals who have responded to the primary vaccination. Current recommendations include booster doses only for patients undergoing hemodialysis.

Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients.

Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7ng/mL before therapy, and 1-year virological response were predictive of HCC development. Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

AST to Platelet Ratio Index Predicts Mortality in Hospitalized Patients With Hepatitis B-Related Decompensated Cirrhosis.

Aspartate aminotransferase to platelet ratio index (APRI) has originally been considered as a noninvasive marker for detecting hepatic fibrosis in patients with chronic hepatitis B and C. APRI has been used for predicting liver-related mortality in patients with chronic hepatitis C virus infection or alcoholic liver disease. However, whether APRI could be useful for predicting mortality in chronic hepatitis B virus (HBV) infection remains unevaluated. This study aims to address this knowledge gap.A total of 193 hospitalized chronic HBV-infected patients (cirrhosis, n = 100; noncirrhosis, n = 93) and 88 healthy subjects were retrospectively enrolled. All patients were followed up for 4 months. Mortality that occurred within 90 days of hospital stay was compared among patients with different APRI. APRI predictive value was evaluated by univariate and multivariate regression embedded in a Cox proportional hazards model.APRI varied significantly in our cohort (range, 0.16–10.00). Elevated APRI was associated with increased severity of liver disease and 3-month mortality in hospitalized patients with HBV-related cirrhosis. Multivariate analysis demonstrated that APRI (odds ratio: 1.456, P < 0.001) and the model for end-stage liver disease score (odds ratio: 1.194, P < 0.001) were 2 independent markers for predicting mortality.APRI is a simple marker that may serve as an additional predictor of 3-month mortality in hospitalized patients with HBV-related decompensated cirrhosis.

PS138 - High Mortality in Chronic Hepatitis C Patients in Sweden Compared to Matched Controls - A Nationwide Population-Based Register Study from 1997 till 2013

PS138 - High Mortality in Chronic Hepatitis C Patients in Sweden Compared to Matched Controls - A Nationwide Population-Based Register Study from 1997 till 2013

The use of Chinese herbal medicines associated with reduced mortality in chronic hepatitis B patients receiving lamivudine treatment

Ethnopharmacological relevanceLamivudine associated mutation and resistance reduces the effect of anti-hepatitis B virus. Pharmacological studies in cell and animal model suggest that Chinese herbal medicines (CHMs) have anti-hepatitis B virus effect. Observational studies offer mixed results. The aim of this study was to evaluate the relation between the use of CHMs and outcome in patients with chronic hepatitis B receiving lamivudine treatment and further estimate the association of Jia-Wei-Xiao-Yao-Sang (JWXYS) use with mortality of those patients. Materials and methodsWe conducted a cohort study among patients age 20–90 years within a National Health Insurance Healthcare system. Information on the use of CHMs and covariates were obtained from Taiwan National Health Insurance Research Database. We used Cox proportional hazards models to estimate the hazard ratio and 95% confidence intervals (95% CI) for all-cause mortality among CHMs users compared to nonusers. ResultsAmong 1037 patients studied from 2004 to 2011, median follow-up time 5.3 years and 88 deaths were identified. During the study period, 49% of patients used CHMs and the median duration of use was 2.4 years. We found that significant difference on all-cause mortality among CHMs users (aHR=0.45, 95% CI: 0.27–0.76) compared to CHMs nonusers. All-cause mortality also differed by JWXYS use (aHR=0.26, 95% CI: 0.08–0.83). ConclusionsThis study reveals that the use of CHMs may lower the risk of death in patients with chronic hepatitis B receiving lamivudine treatment. Further randomized-controlled trials are required to validate these findings.

Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liver-unrelated mortality in chronic hepatitis C patients.

Various inflammatory cytokines and adipokines have been implicated in hepatitis C virus (HCV)-mediated liver disease, and interleukin-6 (IL-6) and adiponectin may play key roles. In addition, these factors may be associated with chronic hepatitis C (CHC)-induced extrahepatic manifestations. However, little data are available on the role of these factors on future outcomes of CHC patients. This study aims to evaluate the impact of serum levels of IL-6 and adiponectin on all-cause mortality, liver-related mortality, and liver-unrelated mortality. A long-term follow-up study was conducted, consisting of 325 CHC patients, for which we previously reported positive associations between these factors (Serum levels of IL-6 and adiponectin) and hepatocellular carcinoma (HCC) development. During the follow-up period (mean, 13.0 year), there were 92 events consisting of 91 deaths (liver related, 72; liver unrelated, 19) and 1 liver transplantation due to liver failure. High IL-6 and adiponectin levels, defined as being higher than each median value at baseline, were associated with significantly higher incidences of not only HCC development but also all-cause mortality. Interestingly, high IL-6 was strongly associated with only liver-related mortality, whereas high-serum adiponectin was associated with not only liver-related, but also liver-unrelated mortality. Multivariate analysis identified high IL-6 as an independent risk factor for liver-related mortality and high adiponectin as an independent risk factor for liver-unrelated mortality. High serum levels of IL-6 and adiponectin were associated with higher all-cause and liver-related mortality in CHC patients. In addition, high adiponectin was associated with liver-unrelated mortality. The measurement of these factors may provide information useful for predicting future outcomes in CHC patients.

Past Exposure to Hepatitis B

Chronic hepatitis B has been shown to increase mortality, but association of past exposure to hepatitis B and mortality has not been studied well. The aim of this study was to evaluate the risk of overall and liver-related mortality in individuals with past exposure to hepatitis B. The National Health and Nutrition Examination Survey III (NHANES III) and its related public linked mortality files were used for this study. The participants with presence of anti-HBc ± anti-HBs, in absence of hepatitis B surface antigen were considered to have previous exposure to hepatitis B. The overall mortality from past exposure to hepatitis B was assessed in participants without any chronic liver diseases (CLD) and in participants with chronic hepatitis C, alcoholic liver disease (ALD), and nonalcoholic fatty liver disease. The Cox proportional regression analysis was used to calculate adjusted hazard ratios. A total of 15,650 individuals were included in the analyses. Past exposure to hepatitis B was an independent predictor of increase in overall mortality in individuals without CLD [adjusted hazard ratio (aHR)=1.29; 95% confidence interval (CI), 1.06-1.56; P=0.012] and those with ALD (aHR=2.25; 95% CI, 1.20-4.23; P=0.013). It was also an independent predictor of liver-related mortality in ALD cohort (aHR=7.75; 95% CI, 2.56-23.48; P<0.001). Past exposure to hepatitis B did not correlate with a significant increase in overall or liver-related mortality in chronic hepatitis C or nonalcoholic fatty liver disease cohorts. Past exposure to hepatitis B is associated with significant increase in overall mortality among individuals with ALD and those without CLD.