Peripheral blood toll-like receptor 4 correlates with rapid virological response to pegylated-interferon and ribavirin therapy in hepatitis C genotype 1 patients.

BACKGROUND: Toll-like receptors (TLRs) are effectors of the innate immune system that are able to recognize hepatitis C virus (HCV) and give rise to an immune response. Failure of interferon (IFN)-α-based treatment is related to host immunity. Therefore, we sought to study the clinical importance of TLRs in HCV genotype 1 patients who received pegylated IFN (PEG-IFN) plus ribavirin (RBV) therapy. METHODS: We enrolled 79 treatment-naïve patients with HCV genotype 1. Patients completed a 24- to 48-week course of response-guided therapy. Peripheral blood monocyte (PBMC) expression of mRNA for TLRs 2, 3, 4, 7, and 9 was quantified by real-time PCR before therapy. TLR mRNA expression is shown as a log ratio relative to GAPDH mRNA (log 2 (-(∆Ct))). RESULTS: Forty-five patients (57.0 %) showed a rapid virological response (RVR). Univariate analysis revealed that TLR 2, 3, 4, 7, and 9 were significantly lower in the RVR group than in the non-RVR group (P = 0.001, 0.014, < 0.001, 0.008, and 0.001, respectively). Multivariate analysis revealed that TLR 4 < -2 log (OR: 7.17, 95 % CI: 1.70-30.34, P = 0.007) was an independent predictor for RVR. In addition, levels of TLR 2, 3, 4, 7, and 9 were positively correlated with HCV viral load (P = 0.009, 0.013, < 0.001, 0.007, and 0.001, respectively). CONCLUSIONS: A low level of TLR 4 mRNA in PMBCs was correlated with RVR, which indicates that TLR4 may play a critical role in HCV recognition and activation of innate immunity. TLR expression levels were correlated with HCV viral load, indicating that TLR activation upon exposure to HCV may subsequently limit HCV replication.

Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up.

UNLABELLED: Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared with HCV-monoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5-year follow-up study. Patients with active HCV genotype 1, both HBV-coinfected (n = 97) and HBV-monoinfected (n = 110), underwent 48-week combination therapy with peginterferon alfa-2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV-coinfected (n = 64) and monoinfected (n = 50) patients underwent 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow-up; 264 (89.5%) patients agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 ± 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV-coinfected patients and one HCV genotype 2/3-monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group. CONCLUSION: Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;).

Hepatitis B virus genotype B results in better immediate, late and sustained responses to peginterferon-alfa in hepatitis-B-e-antigen-positive patients.

BACKGROUND AND AIMS: This study investigated outcome predictors in hepatitis-B-e-antigen (HBeAg)-positive chronic hepatitis B patients treated with peginterferon alfa-2a. METHODS: A total of 88 HBeAg-positive patients receiving peginterferon alfa-2a for 6 months and followed up for at least 24 weeks were prospectively analyzed. Precore and core promoter genes of hepatitis B virus (HBV) were sequenced from the serial serum samples of 88 patients. RESULTS: After 24 weeks of follow up, 38.6% and 28.4% of patients achieved HBeAg clearance and combined response, respectively. Multivariate analysis disclosed that pretreatment HBeAg sample to cut-off (S/Co) ratio ≤ 200, alanine aminotransferase > 200 IU/mL, HBV genotype B and T1846 were independent factors for HBeAg clearance, and HBeAg S/Co ratio ≤ 200 and HBV genotype B were major determinants for combined response. HBeAg S/Co ratio ≤ 10 at week 12 of therapy was the useful factor for treatment response and had a greater power (P = 0.012) to predict HBeAg clearance than HBV DNA. Patients with HBeAg clearance had a higher frequency of A1896 mutation at baseline and during therapy than those without HBeAg clearance, and the frequency of A1896 decreased during treatment. During follow up, delayed HBeAg seroconversion and reactivation of HBV after HBeAg clearance were observed in eight non-responders and 20 patients with HBeAg clearance, respectively. HBV genotype B was a significant factor to predict both responses. CONCLUSIONS: Pretreatment HBeAg S/Co ratio ≤ 200 and HBV genotype B were major determinants for treatment response to peginterferon. Genotype-B-infected patients had higher probability of delayed HBeAg clearance and sustained response. Rapid decrease of HBeAg titer was useful on treatment predictor.

Reversal of hypolipidemia in chronic hepatitis C patients after successful antiviral therapy.

BACKGROUND/PURPOSE: Chronic infection with the hepatitis C virus (HCV) is associated with impaired lipid metabolism. The aim of this study was to determine the impact of antiviral response on the serial change of serum lipids in chronic HCV patients. METHODS: A total of 165 consecutive patients with HCV infection were prospectively enrolled. Serum total cholesterol (TC) and triglyceride (TG) levels in these subjects were compared with age, sex and body mass index-matched healthy individuals and 55 patients with chronic infection with hepatitis B virus (HBV). Serum lipid levels were measured in 143 patients with chronic HCV infection receiving pegylated interferon plus ribavirin therapy at baseline, at the end of treatment, and at week 24 after the end of treatment. RESULTS: Patients with chronic HCV infection had significantly lower total TC and TG levels than normal controls (both p < 0.001). Serum TC levels were lower in HCV patients than in those infected with HBV (p < 0.001). Pretreatment serum lipid levels were not independent factors associated with sustained virological response (SVR). Among patients achieving a SVR, serum TC and TG levels significantly increased from 165 ± 30 mg/dL and 100 ± 47 mg/dL at baseline to 191 ± 36 mg/dL (p < 0.001) and 116 ± 77 mg/dL (p = 0.029) at week 24 posttreatment, whereas no evident change in lipid profile occurred in the non-SVR group. CONCLUSION: Our data suggest that chronic HCV infection is associated with hypocholesterolemia and hypotriglyceridemia, which can be reversed by successful eradication of HCV. The clinical significance of hypolipidemia reversal among SVR patients, such as the risk of coronary artery or cerebral vascular disease, should be further investigated.

HBsAg profiles in patients receiving peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses.

BACKGROUND: With use of peginterferon alfa-2a and ribavirin combination therapy in patients with dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, 11.2% of patients achieved clearance of hepatitis B surface antigen (HBsAg) at 6 months after treatment; however, reactivation of HBV DNA was observed in 36.3%. We investigated the predictive potential of HBsAg quantification. METHODS: HBsAg quantification was performed in 120 e antigen-negative patients dually infected with HBV and hepatitis C virus and treated with peginterferon alfa-2a/ribavirin for 48 weeks (HCV genotype 1; n = 74) or 24 weeks (HCV genotype 2/3; n = 46). HBsAg was quantified at baseline, week 4, week 12, end of treatment, and 24 weeks after treatment. RESULTS: The baseline median serum HBsAg level was 120 IU/mL and decreased gradually during treatment. Low baseline HBsAg was significantly associated with HBsAg clearance (40% for HBsAg level 20 IU/mL vs 2.2% for HBsAg level >20 IU/mL; P < .05). A decrease in HBsAg level from baseline to week 12 of 50% was associated with a reduced likelihood of HBV DNA reactivation in patients with baseline undetectable serum HBV DNA (positive predictive value, 89.5%). CONCLUSIONS: HBsAg quantification appears to be a useful indicator of posttreatment outcome in patients dually infected with HBV and hepatitis C virus.

Peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses.

BACKGROUND & AIMS: Dual chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is common in areas endemic for either virus. Combination therapy with ribavirin and pegylated interferon (peginterferon) is the standard of care for patients with HCV monoinfection. We investigated the effects of combination therapy in patients infected with both HBV and HCV (genotypes 1, 2, or 3). METHODS: The study included 321 Taiwanese patients with active HCV infection; 161 also tested positive for hepatitis B surface antigen (HBsAg) and 160 were HBsAg-negative (controls). Patients with HCV genotype 1 infection received peginterferon alfa-2a (180 mug) weekly for 48 weeks and ribavirin (1000-1200 mg) daily. Patients with HCV genotypes 2 or 3 received peginterferon alfa-2a weekly for 24 weeks and ribavirin (800 mg) daily. At 24 weeks posttreatment, patient samples were examined for a sustained virologic response (SVR) against HCV (serum HCV levels decreased to <25 IU/mL). RESULTS: In patients with HCV genotype 1 infection, the SVR was 72.2% in dually infected patients vs 77.3% in monoinfected patients after treatment. For patients with HCV genotype 2/3 infections, the SVR values were 82.8% and 84.0%, respectively, after treatment. Serum HBV DNA eventually appeared in 36.3% of 77 dual-infected patients with undetectable pretreatment levels of HBV DNA; this was not accompanied by significant hepatitis. Posttreatment HBsAg clearance was observed in 11.2% of 161 dual-infected patients. CONCLUSIONS: Combination therapy with peginterferon alfa-2a and ribavirin is equally effective in patients with HCV monoinfection and in those with dual chronic HCV/HBV infection.

Ropeginterferon alfa-2b every 2 weeks as a novel pegylated interferon for patients with chronic hepatitis B.

BACKGROUND: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8-14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. METHODS: Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 µg (group 1), q2w 450 µg (group 2) or q1w PEG-IFN alfa-2a 180 µg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). RESULTS: The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 µg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). CONCLUSION: In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B.

[Comparison of condylar position between Angle Class I and Class II malocclusion in teenagers].

PURPOSE: To analyze and compare the difference of condylar position between Angle Class I and Class II malocclusion patients using cone-beam CT (CBCT). METHODS: Thirty Class I patients, 30 Class II division 1 patients and 30 Class II division 2 patients were selected in this study. Each patient underwent CBCT. The images in the oblique position perpendicular to the condyloid process were reconstructed by Examvision software. The joint space was measured by Exam Vision software. The data were processed with SPSS17.0 software package. RESULTS: The upper joint space was larger in Class II, the posterior joint space was smaller in Class II patients; and in Class II division 1 patients, both of the upper and anterior joint spaces were larger than in Class II division 2 patients，the differences were significant (P<0.05). The length of condyle was longer in Class I patients than in Class II patients. CONCLUSIONS: The condylar position in Class II division 2 patients was lower and further backward. The length of condyle is shortest in Class II division 2 patients.

Comparison of Therapeutic Response and Clinical Outcome between HCV Patients with Normal and Abnormal Alanine Transaminase Levels.

BACKGROUND AND AIMS: Patients with chronic hepatitic C (HCV) infection and normal serum alanine transaminase (ALT) levels were considered to have mild disease. In Taiwan, these patients were not suggested for interferon (IFN) based therapies. The aim of study is to compare therapeutic outcomes between HCV patients with normal and elevated ALT levels. METHODS: We conducted a retrospective study on 3241 HCV patients treated by IFN based therapies. Patients with normal ALT levels were classified as group A (n = 186) while those with elevated ALT levels were group B (n = 3055). RESULTS: At baseline, incidence of diabetes mellitus, low platelet counts and cirrhosis were significantly higher in group B patients. The sustained virologic response (SVR) rate was comparable between the 2 groups (65.3% vs. 65.3%, P = .993). But significantly higher incidence of HCC development after HCV treatment was observed in group B (7.4% vs. 3.2%, P = .032). No significant differences with respect to the outcome of liver decompensation, spontaneous bacterial peritonitis, and mortality were noted between 2 groups. Multivariate analysis showed younger age, female gender, non-HCV genotype 1, lower viral load, higher platelet counts and non-cirrhosis were favorable factors for achieving SVR, rather than ALT levels. Further analysis revealed older age, cirrhosis, lower platelet levels and non- peg-interferon treatment are risk factors of HCC development. CONCLUSIONS: HCV patients with normal ALT levels had similar response to antiviral therapy and low rate of HCC development after therapy. Antiviral therapies begun at early course of HCV infection may be beneficial to prevent disease progression.

[A study on the thickness of buccal bone in the mandible of different vertical facial type in adults using cone-beam CT].

PURPOSE: To provide some references of using micro-implant anchorage in clinical orthodontic treatment, the thickness of buccal bone of mandible of different vertical facial type in adults with cone-beam CT (CBCT) were measured. METHODS: Initial 3-dimensional images of 45 adult patients (15 men, 30 women)were reoriented by using a standardized protocol, and divided into 3 groups by angle of mandibular plane (G1: high angle, 15 patients; G2: average angle, 15 patients; G3: low angle, 15 patients). After signing the informed consent form, three measurement points were defined at 4, 6, and 8mm from the alveolar crest in each measurement area. Statistical analysis was performed with SPSS11.0 software package. RESULTS: The thickness of buccal bone in mandible was thinner in G1 than in G2, and was thinnest in G3. The cortical bone thickness was thickest at the 8 mm level and thinnest at the 4mm level. CONCLUSIONS: The study suggested that the cortical bone thickness at 4mm level from the alveolar crest was safe for implantation. It is more stable when the distance of implants was more away from the alveolar crest. Patients with low mandibular plane angle should use self-tapping micro-implant anchorage. Supported by Nantong Science and Technology Fund (HS2013033).

Neutrophil-to-lymphocyte ratio as a predictor of response to peginterferon plus ribavirin therapy for chronic hepatitis C.

We aimed to determine whether neutrophil-to-lymphocyte ratio (NLR) could be a predictor of antiviral response in chronic hepatitis C patients. A total of 602 consecutive patients (genotype 1, n = 263; genotype 2, n = 297; others/unknown, n = 42) receiving response-guided therapy with peginterferon plus ribavirin were recruited. NLR was related to clinical and virological features and to treatment outcome. Rapid virological response (RVR) and sustained virological response (SVR) were achieved in 436 (73%) and 458 (76%) of the patients, respectively. Higher NLR (≥1.42) was found to be associated with higher prevalence of DM (P = 0.039) and higher hepatitis C viral load (P = 0.002) and white cell count (P < 0.001). NLR was significantly lower in patients with RVR and SVR compared to those without (P = 0.032 and 0.034, resp.). However, NLR was not an independent factor by multivariate analysis. In the subgroup analysis, higher NLR (≥1.42) (odds ratio, 0.494, P = 0.038) was an independent poor predictor of SVR in genotype 2 patients but was not in genotype 1 patients. In conclusion, NLR is a simple and easily accessible marker to predict response to peginterferon plus ribavirin therapy for chronic hepatitis C genotype 2.

A double-blind randomized controlled study to evaluate the efficacy of low-dose oral interferon-alpha in preventing hepatitis C relapse.

Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4-1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy.

[Comparative study on the morphology of crown, alveolar ridge crest and gingival in maxillary anterior region].

OBJECTIVE: To investigate the correlation among the morphology of crown, alveolar ridge crest and gingiva in maxillary anterior region of adults and to provide anatomical basis for clinical implant esthetics. METHODS: Sixty Han-Chinese with healthy peridontium were selected in this study. The curvature of labial alveolar crest, the length and height of inter-proximal bone were measured on 3-D model reconstructed from cone-beam CT (CBCT) images, and the curvature of free gingiva, the width and height of inter-dental papilla and central incisor crown were evaluated on casts. The ratio of crown width to height was ranked and the 10 ranked highest were categorized as group Short-Wide (SW), the 10 ranked lowest were selected as group Long-Narrow (LN). RESULTS: In maxillary anterior region, the curvature angle of both alveolar crest and marginal gingiva were significantly different among different tooth regions, but the alveolar and gingival curvature was significantly correlated in the same region (P < 0.05). The morphology of inter-proximal bone and papilla was significantly correlated (P < 0.01), except the region between central and lateral incisors (P = 0.625, P > 0.05). Compared to group SW, group LN formed a pronounced scalloped contour of gingival margin (P = 0.002) and slender inter-dental papilla (P = 0.000). CONCLUSIONS: The free gingival curvature and inter-dental papillary morphology are significantly correlated with the morphology of crown and alveolar ridge crest in maxillary anterior region of Han-Chinese. Individuals with long-narrow crown, pronounced scalloped marginal gingiva and slender inter-dental papilla are susceptible to risk implant esthetics.

Sustained HCV clearance by interferon-based therapy reduces hepatocellular carcinoma in hepatitis B and C dually-infected patients.

BACKGROUND: Recent studies have indicated that interferon (IFN) or pegylated interferon (PEG-IFN) plus ribavirin therapy can achieve sustained virological response (SVR) against HCV equally in dual HBV-HCV infection and in HCV monoinfection. Whether these therapies can reduce hepatocellular carcinoma (HCC) development in dual HBV-HCV infection remains unclear. METHODS: A total of 135 dually-infected patients with active hepatitis C receiving IFN or PEG-IFN plus ribavirin therapy were enrolled. The cumulative incidence of HCC was compared to that in 1,470 HCV-monoinfected patients. RESULTS: Based on the Cox proportional hazards model, dual infection was an independent factor for HCC development in all 1,605 chronic hepatitis C patients with or without positive hepatitis B surface antigen receiving IFN or PEG-IFN plus ribavirin (hazard ratio (HR)=1.864, 95% CI 1.052-3.303; P=0.033). In dually-infected patients, HCC developed in 4 of 96 with HCV SVR and 11 of 39 without HCV SVR (P < 0.001) after a median follow-up of 4.6 years. Age (HR=1.175, 95% CI 1.070-1.291; P=0.001) and non-HCV-SVR (HR=7.874, 95% CI 2.375-26.32; P=0.001) were independent factors for HCC development. Subgroup analysis showed that HCC occurrence was lower in patients with HCV SVR and HBV DNA levels < 2,000 IU/ml at the end of treatment or follow-up compared to those with HCV SVR and HBV DNA levels ≥ 2,000 IU/ml (P=0.034) and those without HCV SVR (P<0.001). CONCLUSIONS: Sustained HCV clearance by IFN or PEG-IFN plus ribavirin therapy may significantly reduce HCC in HBV-HCV dually-infected patients, whereas persistence or reactivation of HBV decreases the benefit of HCV SVR.

Seroprevalence of anti-HCV among patients with oral lichen planus in Southern Taiwan.

A possible association between oral lichen planus (OLP) and hepatitis C virus (HCV) infection has been documented in certain populations such as Japan and Southern Europe; however, the issue remains controversial. The aim of this study was to investigate the prevalence of HCV antibodies among patients with OLP in Southern Taiwan, and to assess the possible association between OLP and HCV infection. All patients enrolled in the study sought care at a hospital dental clinic. Serum samples of 104 patients with OLP and 100 controls with healthy oral mucosa, whose age and gender were matched, were respectively screened for anti-HCV antibodies by the microparticle enzyme immunoassay (AxSYM HCV version 3.0). The prevalence of HCV infection was 22.1% in the study group (23 of 104 OLP patients) and 2% in the control group (2 of 100 control subjects) respectively (P < .001). Eleven of 23 HCV-infected OLP patients (47.8%) were unaware of their HCV infection status in the study. A positive association between OLP and HCV in Southern Taiwan exists, suggesting that routine HCV infection testing of patients with OLP in Southern Taiwan should be considered.

Prevalence and clinical relevance of serum autoantibodies in patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C (CHC) is frequently associated with the presence of serum autoantibodies. The prevalence and clinical relevance of serum autoantibodies in CHC patients and their influence on antiviral treatment have not been well established. METHODS: From February 1999 to July 2004, 460 consecutive adult patients with CHC were studied. Antinuclear antibody (ANA) and smooth muscle antibody (SMA) were determined by indirect immunofluorescence. The presence of these antibodies was related to patient characteristics and to the outcome of 24 weeks of therapy with interferon (IFN) alfa-2b (n=376) or pegylated- IFN alfa-2b (n=84) plus ribavirin. RESULTS: The prevalence of ANA and SMA was 7.4% and 19.3%, respectively. Seropositivity for ANA and/or SMA was associated with old age and high aspartate aminotransferase (AST) levels. The rates of sustained virological response and early withdrawal of therapy were comparable between autoantibody- positive and -negative patients. None of the autoantibody-positive patients experienced a flare-up of transaminase during treatment, or developed severe systemic autoimmune disease. CONCLUSION: Serum ANA and/or SMA-positive HCV-infected patients are older, and have higher disease activity and severity than their negative counterparts. However, the presence of ANA or SMA did not influence the response to combination antiviral therapy, which is safe and effective in autoantibody--positive CHC patients.

Hepatitis C virus genotypes: clinical relevance and therapeutic implications.

The incidence of hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) has been increasing in several countries including Taiwan. There are six main genotypes, each of which contains closely related subtypes. Molecular epidemiological studies have shown marked differences in the genotype distribution by geographical region and between patient groups. HCV genotype 1 may play a role in the development of HCC, although some studies have argued against this. A sustained virological response secondary to interferon monotherapy or interferon/ribavirin combination therapy may reduce the risk of HCC and improve survival in chronic hepatitis C patients. The HCV genotypes are associated with therapeutic response. Rapid virological response is also a predictor of therapeutic response. Although viral characteristics have consistently been shown to be important predictors of treatment response, identification of additional host immune and genetic factors involved in determining the outcome of antiviral therapy is necessary. Newly developed bio-techniques (microarray, proteomes, bioinformatics), drugs, and treatment strategies may elucidate the pathogenesis and improve the therapeutic response in HCV infection.

Interstitial pneumonitis after combination therapy with pegylated interferon alpha-2b and ribavirin for chronic hepatitis C.

Pulmonary toxicity is a rare but potentially fatal side effect occurring during interferon (IFN) alpha treatment for chronic hepatitis C. We present a 47-year-old woman who had chronic hepatitis C and was treated with pegylated IFN alpha-2b in combination with ribavirin, with a good virological response by week 10 of therapy. Then the patient began to complain of dyspnea on exertion and a dry cough. A diagnosis of interstitial pneumonitis was made according to the results of chest X-rays, high resolution computed tomography and bronchoalveolar lavage analysis. Pegylated IFN alpha-2b has a longer absorption and elimination half-life than conventional IFN alpha-2b and a comparable potency to conventional IFN alpha-2b. Although the tolerability of pegylated IFN alpha is comparable to that of conventional IFN alpha, pulmonary toxicity may occur more frequently with long-acting pegylated IFN alpha therapy at an inappropriately high dose. Based on a MEDLINE search up to 2004, we believe that this is the first reported case of a patient recovering from interstitial pneumonitis associated with pegylated IFN alpha-2b for chronic hepatitis C. Physicians should keep in mind the possibility of this complication when treating chronic hepatitis C patients with pegylated IFN alpha-2b and ribavirin combinational therapy.

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis.

BACKGROUND AND AIMS: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long-term reversibility of thyroid dysfunction. METHODS: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN-alpha-2b, 3 or 5 million units thrice weekly, or pegylated (PEG)-IFN-alpha-2b 80 or 100 microg weekly combined with ribavirin 1-1.2 g daily for 24-48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. RESULTS: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6-5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG-IFN-treated patients (49/391 vs 9/70; P = 1.00). Under a nested case-control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age- (+/- 5 years) and sex-matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2-27.9). Ten patients ( approximately 2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. CONCLUSIONS: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long-term thyroid dysfunction may persist in a small group of patients ( approximately 2%).

Anemia associated with antiviral therapy in chronic hepatitis C: incidence, risk factors, and impact on treatment response.

BACKGROUND: One major side effect of combination antiviral therapy is the development of anemia, which is more severe among the Asian population. We conducted this large-scaled study to explore the incidence, risk factors, and impact on treatment response of anemia in chronic hepatitis C patients receiving combination antiviral therapy. METHODS: Four hundred and sixty-six chronic hepatitis C patients were treated with interferon-alpha-2b (IFN-alpha-2b) three or five million units thrice weekly, or pegylated-IFN-alpha-2b 1-1.5 microg/kg weekly plus ribavirin (1000-1200 mg/day) for 24 weeks. Severe anemia was defined as hemoglobin concentration <10 g/dl. RESULTS: The mean decrease of hemoglobin was 3.9+/-1.3 g/dl. Thirty-nine percent of patients had developed severe anemia during therapy. Stepwise logistic regression analysis revealed that old age (> or =50 years) (odds ratio [OR]=1.935, P=0.001) and baseline hemoglobin level (> or =14 g/dl) (OR=2.975, P<0.001) were significantly correlated with maximal decreases in hemoglobin. Using Cox's regression analysis, pretreatment platelet counts (<150 000/mm(3)) (OR=1.821, P<0.001), old age (> or =50 years) (OR=1.789, P=0.001), female gender (OR=1.739, P<0.001), and low body weight (<65 kg) (OR=1.493, P=0.027) were independent factors contributing to severe anemia. There was a significant linear correlation between the sustained virological response (SVR) rate and the time of severe anemia during therapy (r=0.774, P=0.003), especially among genotype 1 patients (r=0.960, P<0.001). CONCLUSION: Careful monitoring of hemoglobin level is necessary in patients who are old, female and have low body weight and platelet counts. Development of severe anemia was significantly correlated with the SVR.