Influence of quasispecies on virological responses and disease severity in patients with chronic hepatitis C

AIM:To elucidate the influence of quasispecies on virological response and disease severity in patients with chronic hepatitis C. METHODS:Forty seven patients with hepatitis C [32 with chronic active hepatitis (CAH), 9 with cirrhosis, and 6 with hepatocellular carcinoma (HCC)] were screened for the presence of quasispecies by single stranded conformational polymorphism (SSCP) analysis in the hypervariable region (HVR) and non-structural 5B (NS5B) viral genes of hepatitis C virus. The 41 patients excluding those with HCC were on therapy and followed up for a year with the determination of virological response and disease severity. Virus isolated from twenty three randomly selected patients (11 non-responders and 12 showing a sustained virological response) was sequenced for the assessment of mutations. RESULTS:The occurrence of quasispecies was proportionately higher in patients with HCC and cirrhosis than in those with CAH, revealing a significant correlation between the molecular evolution of quasispecies and the severity of disease in patients with hepatitis C. The occurrence of complex quasispecies has a significant association (P < 0.05) with the non-responders, and leads to persistence of infection. Significant differences (P < 0.05) in viral load (log10 IU/mL) were observed among patients infected with complex quasispecies (CQS), those infected with simple quasispecies (SQS) and those with no quasispecies (NQS), after 12 wk (CQS-5.2 ± 2.3, SQS-3.2 ± 1.9, NQS-2.8 ± 2.4) and 24 wk (CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, NQS-2.1 ± 2.3) in the HVR region. However, a statistically significant difference (P < 0.05) was observed between the viral loads of patients infected with CQS and those infected with NQS in NS5B viral gene after 24 wk (CQS-3.9 ± 2.2, SQS-3.0 ± 2.2, and NQS-2.1 ± 2.3) and 48 wk (CQS-3.1 ± 2.7, SQS-2.3 ± 2.4, NQS-2.0 ± 2.3) of therapy. Disease severity was significantly associated with viral load during therapy. The strains isolated from non-responders showed close pairing on phylogeny based on the NS5B gene, but dissimilar HVR regions. This revealed the possibility of the selection of resistant strains during the evolution of quasispecies in NS5B. CONCLUSION:Viral quasispecies may be an important predictor of virological responses to combination therapy in patients with chronic hepatitis C. Complex quasispecies and resistant strains may lead to high viral loads during therapy, with a concerted effect on disease severity.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

Despite achieving a high cure rate with the direct-acting antivirals(DAAs)in hepatitis C treatment,further research is needed to identify additional benefits of the DAA therapy.The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs,who also achieved sustained virologic response.By the fibrosis-4(FIB-4)index,patients were categorized based on their baseline fibrosis levels,and the improvement in fibrosis was analyzed in both short-term(9-26 weeks)and long-term(≥36 weeks)follow-up.The results showed a significant decrease in the FIB-4 index,indicating an improvement in liver fibrosis,in 63.0%and 67.6%of the patients during the short-term and long-term follow-up,respectively.Short-term improvement was associated with factors including ribavirin usage,blood cholinesterase levels,alanine transaminase levels,albumin levels,and the baseline FIB-4 index,while long-term improvement was associated with factors such as aspartate transaminase levels,total protein level,and the baseline FIB-4 index.The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis,which will provide crucial insights for enhancing patient care in hepatitis C management.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Influence of nonalcoholic fatty liver disease on the therapeutic effect of nucleoside(acid)analogs for hepatitis B virus

BACKGROUND The effect of nonalcoholic fatty liver disease(NAFLD)on the efficacy of nucleoside analogues(NAs)in antiviral therapy for patients with chronic hepatitis B(CHB)remains controversial.AIM To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.METHODS Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs.CHB patients were followed up for more than 28 months after initial antiviral treatment,and further validation was performed using different viral load populations.RESULTS NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs(odds ratio=1.777,P=0.017).In our subsequent analysis focusing on CHB patients with high viral load,the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group(16.8±6.1 vs 13.0±6.8,P<0.05).During the 24-month period of antiviral treatment with NAs,hepatitis B virus(HBV)DNA levels decreased slowly in the NAFLD group,and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group(P=0.001).Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.CONCLUSION Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.

Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis

AIM To evaluate the safety and efficacy of tenofovir disoproxil fumarate(TDF) as a first-line therapy in decompensated liver disease. METHODS We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS The 1-year complete virological response(CVR) and Hepatitis B e antigen(HBe Ag) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBe Ag seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus(HBV) DNA in both groups, but CVR was higher in the compensated group(88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh(CTP) and model for end-stage liver disease(MELD) scores in decompensated group(P < 0.001). Of the 57 decompensated patients, 39(68.4%) achieved CTP class A and 27(49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/d L increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively(P < 1.000).CONCLUSION TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.

Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen

Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host&#x02019;s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as &#x0201c;hepatitis C-associated dysmetabolic syndrome&#x0201d; (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.

Vitamin D deficiency in chronic liver disease

Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

Elevated serum interleukin-38 level at baseline predicts virological response in telbivudine-treated patients with chronic hepatitis B

AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Serum leptin and ghrelin in chronic hepatitis C patients with steatosis

AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.

Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues

Quantification of hepatitis B surface antigen(HBsAg)has been suggested to be helpful in the management of chronic hepatitis B(CHB)patients.Nucleos(t)ide analogs(NAs)are the therapy of choice for CHB and are used in the majority of CHB patients.NAs are able to induce hepatitis B virus(HBV)viral suppression,normalization of alanine aminotransferase(ALT)levels,and improvement in liver histology.Automated quantitative assays for serum HBsAg have recently become available,facilitating standardized quantification of serum HBsAg.This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs.Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV,and can therefore be used to predict therapeutic response.NA treatment typically induces a less rapid decline in HBsAg than interferon treatment;it has been estimated that full HBsAg clearance can require decades of NA treatment.However,a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg.Currently,there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy.This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3

Hepatitis C virus(HCV) infection is a common chronic liver disease worldwide.Non-alcoholic fatty liver disease and insulin resistance(IR) are the major determinants of fibrosis progression and response to antiviral therapy.The pathogenetic link between IR and chronic HCV infection is complex,and is associated with HCV genotype.Liver steatosis is the most common in the patients infected with genotype 3 virus,possibly due to direct effects of genotype 3 viral proteins.To the contrary,hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism,involving IR.In HCV genotype 3,liver steatosis correlates with viral load,reverts after reaching the sustained virologic response and reoccurs in the relapsers.A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.

Partial virological response to three different nucleotide analogues in naive patients with chronic hepatitis B

BACKGROUND： The definition of partial virological response （PVR） was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues （NA） is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir mono- therapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS： We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July2013. RESULTS： Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 （6-147） months. PVR rates at 24 weeks were similar among three NAs （lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P--0.981）. For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough （VBR） for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR （HR： 3.09; 95% CI： 1.09-8.74; P=0.034）; also lamivudine treated patients older than 50 years seemed to have a tendency for VBR （HR： 2.80; 95% CI： 0.99-8.18; P=0.052）. A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations.CONCLUSIONS： Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals

BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals(DAAs)and patient prognosis.Non-invasive techniques to assess liver fibrosis are becoming important.Recently,serum Mac-2 binding protein glycosylation isomer(M2BPGi)was identified as a non-invasive marker of liver fibrosis.AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C(CHC)treated with DAAs.METHODS From December 2017 to August 2018,80 treatment-naive adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study.For 12 weeks,65 patients were treated with sofosbuvir/daclatasvir,and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic,Cairo,Egypt.We measured serum M2BPGi levels,PAPAS index,fibrosis-4(FIB-4)score and liver stiffness measurements(LSM)at baseline and 12 weeks after the end of treatment.Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.RESULTS All patients achieved sustained virologic response(SVR12)(100%).Serum M2BPGi levels,LSM,FIB-4 score and PAPAS index decreased significantly at SVR12(P<0.05).Serum M2BPGi levels correlated positively with LSM at baseline and SVR12(P<0.001).At baseline,compared with the FIB-4 score and PAPAS index,M2BPGi was the best marker to distinguish patients with grade F4 fibrosis(AUC=0.801,P<0.001),patients with grade F2 from grade F0-1 fibrosis(AUC=0.713,P=0.012),patients with grade F3-4 from grade F0-2 fibrosis(AUC=0.730,P<0.001),and patients with grade F2-4 from grade F0-1 fibrosis(AUC=0.763,P<0.001).At SVR12,M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis(AUC=0.844,P<0.001),patients with grade F3 from grade F0-2 fibrosis(AUC=0.893,P=0.002),patients with grade F3-4 from grade F0-2 fibrosis(AUC=0.891,P<0.001),and patients with grade F2-4 from grade F0-1 fibrosis(AUC=0.750,P<0.001).CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.

Baseline HBsAg predicts response to pegylated interferon-α2b in HBeAg-positive chronic hepatitis B patients

AIM: To evaluate the predictive effect of baseline hepatitis B surface antigen (HBsAg) on response to pegylated interferon (PEG-IFN)-&#x003b1;2b in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

Shear wave elastography in hepatitis C patients before and after antiviral therapy

AIMTo investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR). METHODSA total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (na&iuml;ve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE. RESULTSSW propagation velocity (Vs) was 1.23 &plusmn; 0.14 m/s in the control group, 1.56 &plusmn; 0.32 m/s in the SVR group, and 1.69 &plusmn; 0.31 m/s in the na&iuml;ve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the na&iuml;ve group (P = 0.01417). All four fibrosis markers were higher in the na&iuml;ve group than in the SVR group. In the na&iuml;ve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), &alpha; feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std &beta; = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std &beta; = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std &beta;= 0.2969, P = 0.03363). CONCLUSIONIn hepatitis C patients, liver stiffness is higher in treatment-na&iuml;ve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

Treatment of hepatitis C virus infection

Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co- infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.

Baseline predictors of virological response for chronic hepatitis B patients

AIM： To determine which baseline factors of chronic hepatitis B patients are predictive of virological response to Peginterferon α-2b therapy. METHODS： A total of 21 HBeAg-positive chronic hepatitis B （CriB） patients treated with Peginterferon α-2b were recruited. They were treated with Peginterferon α-2b （0.5-1.0 μg/kg per week） for 24 wk and followed up for 24 wk. Clinical and laboratory data of the patients were determined at pretreatment and at week 12, at 24 during treatment, and at week 48 during follow up. RESULTS： Ten patients achieved a virological response at the end of treatment. Their baseline serum alanine aminotransferase （ALT）, thyroid-stimulating hormone （TSH）, and total thyroxin （TT4） levels were significantly different from those who failed treatment. The positive predictive values （PPV） and negative predictive values （NPV） of ALT, TSH, and TT4 were 75% and 89 %, 75% and 89 %, and 75% and 75%, respectively. Moreover, combinations of the baseline ALT and TT4, ALT and TSH, TT4 and TSH levels had much higher PPV and NPV （86% and 88%, 89% and 100%, 83% and 100%, respectively）.CONCLUSION： Baseline serum ALT, TSH, and TT4 levels, especially in combination, have high predictive values of virological response to Peginterferon α-2b in HBeAg-positive CriB patients.