A Drosophila model of ALS reveals a partial loss of function of causative human PFN1 mutants.

Mutations in the profilin 1 (PFN1) gene are causative for familial amyotrophic lateral sclerosis (fALS). However, it is still not fully understood how these mutations lead to neurodegeneration. To address this question, we generated a novel Drosophila model expressing human wild-type and ALS-causative PFN1 mutants. We show that at larval neuromuscular junctions (NMJ), motor neuron expression of wild-type human PFN1 increases the number of ghost boutons, active zone density, F-actin content, and the formation of filopodia. In contrast, the expression of ALS-causative human PFN1 mutants causes a less pronounced phenotype, suggesting a loss of function of these mutants in promoting NMJ remodeling. Importantly, expression of human PFN1 in motor neurons results in progressive locomotion defects and shorter lifespan in adult flies, while ALS-causative PFN1 mutants display a less toxic effect. In summary, our study provides evidence that PFN1 is important in regulating NMJ morphology and influences survival and locomotion in Drosophila. Furthermore, our results suggest ALS-causative human PFN1 mutants display a partial loss of function relative to wild-type hPFN1 that may contribute to human disease pathogenesis.

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.

[The difference of IL-28B polymorphisms between hepatitis C patients with and without cryoglobulinemia].

OBJECTIVE: To determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia. METHODS: Sixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917, rs12979860, and rs12980275) were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline (prior to treatment initiation), during treatment (4 and 12 weeks after treatment initiation), end of therapy (48 weeks after treatment initiation), and post-treatment (24 weeks after end of therapy). The significance of between-group differences were assessed by the Chi-square and Fisher's exact tests. RESULTS: Cryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than 0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%, P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response. CONCLUSION: Cryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymorphisms, and certain polymorphisms may be related to anti-viral treatment response.

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion.

Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least 2 weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.

A bidirectional switch in the Shank3 phosphorylation state biases synapses toward up- or downscaling.

Homeostatic synaptic plasticity requires widespread remodeling of synaptic signaling and scaffolding networks, but the role of post-translational modifications in this process has not been systematically studied. Using deep-scale quantitative analysis of the phosphoproteome in mouse neocortical neurons, we found widespread and temporally complex changes during synaptic scaling up and down. We observed 424 bidirectionally modulated phosphosites that were strongly enriched for synapse-associated proteins, including S1539 in the autism spectrum disorder-associated synaptic scaffold protein Shank3. Using a parallel proteomic analysis performed on Shank3 isolated from rat neocortical neurons by immunoaffinity, we identified two sites that were persistently hypophosphorylated during scaling up and transiently hyperphosphorylated during scaling down: one (rat S1615) that corresponded to S1539 in mouse, and a second highly conserved site, rat S1586. The phosphorylation status of these sites modified the synaptic localization of Shank3 during scaling protocols, and dephosphorylation of these sites via PP2A activity was essential for the maintenance of synaptic scaling up. Finally, phosphomimetic mutations at these sites prevented scaling up but not down, while phosphodeficient mutations prevented scaling down but not up. These mutations did not impact baseline synaptic strength, indicating that they gate, rather than drive, the induction of synaptic scaling. Thus, an activity-dependent switch between hypo- and hyperphosphorylation at S1586 and S1615 of Shank3 enables scaling up or down, respectively. Collectively, our data show that activity-dependent phosphoproteome dynamics are important for the functional reconfiguration of synaptic scaffolds and can bias synapses toward upward or downward homeostatic plasticity.

[The effect of cryoglobulinemia on the antiviral therapy in patients with chronic hepatitis C].

OBJECTIVE: To investigate the possible influence of cryoglobulinemia on the antiviral effect in chronic hepatitis C patients, who were treated with combination therapy of pegylated interferon alpha-2a and ribavirin. METHODS: Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with ribavirin. Baseline cryoglobulins were detected in the sera by cryoprecipitation. Hepatitis C virus (HCV) genotyping was performed and HCV viral load was detected at baseline, and at 4, 12 weeks during treatment, 24 weeks after cessation of treatment. RESULTS: Eighteen (45.0%) patients infected with HCV were cryoglobulins positive at baseline. Mean serum HCV RNA level in cryoglobulins positive patients was higher than that in cryoglobulins negative patients (6.36+/-0.63 vs. 5.70+/-1.20, P = 0.032). The rapid virological response (RVR) rate was statically different between cryoglobulins positive patients and cryoglobulins negative ones (6/18, 33.3% vs. 15/22, 68.2%, P = 0.028). In contrast, no difference was found in early virological response (EVR) rate between the cryoglobulins positive patients and cryoglobulins negative ones (14/17, 82.4% vs. 18/21, 85.7%, P = 1.0). Sustained virological response (SVR) rate in cryoglobulins positive and cryoglobulins negative was different (0/3, 0 vs 6/6, 100%, P = 0.012). The rate of patients achieved RVR was different between the patients infected with HCV genotype 1 b of two groups (cryoglobulins positive: 2/13, 15.4% vs cryoglobulins negative 14/21; 66.7%, P = 0.005). However, the rate of EVR in patients infected HCV genotype 1 b was not statistically different (cryoglobulins positive: 9/12, 75.0% vs. cryoglobulins negative 17/20; 81.2%, P = 0.647). CONCLUSION: The rates of RVR and SVR achievement in cryoglobulinemia positive CHC patients are lower than those in cryoglobulinemia negative CHC patients.

Homeostatic synaptic scaling establishes the specificity of an associative memory.

Correlation-based (Hebbian) forms of synaptic plasticity are crucial for the initial encoding of associative memories but likely insufficient to enable the stable storage of multiple specific memories within neural circuits. Theoretical studies have suggested that homeostatic synaptic normalization rules provide an essential countervailing force that can stabilize and expand memory storage capacity. Although such homeostatic mechanisms have been identified and studied for decades, experimental evidence that they play an important role in associative memory is lacking. Here, we show that synaptic scaling, a widely studied form of homeostatic synaptic plasticity that globally renormalizes synaptic strengths, is dispensable for initial associative memory formation but crucial for the establishment of memory specificity. We used conditioned taste aversion (CTA) learning, a form of associative learning that relies on Hebbian mechanisms within gustatory cortex (GC), to show that animals conditioned to avoid saccharin initially generalized this aversion to other novel tastants. Specificity of the aversion to saccharin emerged slowly over a time course of many hours and was associated with synaptic scaling down of excitatory synapses onto conditioning-active neuronal ensembles within gustatory cortex. Blocking synaptic scaling down in the gustatory cortex enhanced the persistence of synaptic strength increases induced by conditioning and prolonged the duration of memory generalization. Taken together, these findings demonstrate that synaptic scaling is crucial for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and memory generalization.

[Clinical features and prognosis of decompensated hepatitis C virus related cirrhosis].

OBJECTIVE: To study the clinical features and prognosis of hepatitis C virus (HCV)-related cirrhosis after the first occurrence of complications. METHODS: The clinical data of 89 decompensated HCV-related cirrhosis patients were analyzed. Univariate and multivariate analyses of the factors influencing the clinical decompensation were conducted. RESULTS: Ascites was the most frequent first decompensation (44.9%), followed by upper gastrointestinal bleeding (23.6%), and self-originated peritonitis (20.2%), and hepatic encephalopathy (11.2%). During the follow-up of 62 months (60-66 months) ascites was the most frequent first decompensation (47. 2%), followed by self-originated peritonitis (18.0%), upper gastrointestinal bleeding (15.7%), and hepatic encephalopathy (7.9%). The 5-year survival rates after of the patients with hepatic encephalopathy, ascites, upper gastrointestinal bleeding and self-originated peritonitis as the first decompensated complications were 64.5%, 85.0%, 75.0%, and 83.3% respectively. Multivariate regression analysis showed that esophageal and gastro varices and bilirubin were independently correlated with survival. CONCLUSION: Hepatitis C is a slowly progressing disease. Decompensation occurring in hepatitis C is significantly correlated with survival.

[An analysis of clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas in patients with hepatitis C virus infection].

OBJECTIVE: To study the epidemiological and clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas (HCC) in patients with hepatitis C virus (HCV) infection. METHODS: Eighty-nine compensated and decompensated HCV cirrhosis patients were analyzed and followed-up. The main clinical and laboratory variables were analyzed as incidence factors of HCC with univariate analysis and multivariate analysis regression models. RESULTS: The patients were followed-up for 86 months. Thirty-five of the 89 patients had HCC during the 86 months follow-up. Their five and ten-year cumulative incidences were 16.9% and 40.4% respectively. Of the 35 HCC patients, 4 had a family history of hepatitis C, 12 had a familial history of HCC, and 7 had a history of alcohol ingestion. Five and ten-year cumulative incidences of HCC in patients with hepatic steatosis were 24.6% and 51.0% respectively. Five-year and ten-year cumulative incidences of HCC in patients with non-hepatic steatosis were 8.7% and 26.2% respectively, and the difference in the cumulative incidences between them was significant (P < 0.05). Hepatic steatosis severity was associated with the severity of the cirrhosis. ALT and TBil levels were higher in the HCC group than in the non-HCC group, ALB was lower in the HCC group than in the non-HCC group, and the differences between them were significant (P < 0.05). Child-Pugh score and the severity of the hepatic steatosis during follow-up were independently correlated with HCC. CONCLUSION: HCC is the most important and frequent outcome of chronic hepatitis C cirrhosis. Child-Pugh score and the severity of the hepatic steatosis are related to the risk factors. History of alcohol ingestion and family history of hepatitis C are also related to liver cancer.

[The histopathologic and clinical analysis of viral chronic hepatitis patients with negative serological viral markers].

OBJECTIVE: To analyze the histopathological and clinical features of viral chronic hepatitis patients with negative serological viral markers. METHODS: 62 hepatitis patients with negative serological markers were assayed with serological viral hepatitis markers, liver function test and liver biopsies were enrolled in the study. Serum HBV DNA of HBV cases was analyzed by PCR. Liver specimens were examined by immunohistochemistry for HBsAg and HBcAg. RESULTS: The fit rate of histopathological diagnosis with clinical diagnosis is 53.2%, the fit rate is 69.1% in moderate chronic hepatitis group. The immunohistochemistry showed that HBsAg and/or HBeAg positive rate was 45.2%, 53.6% had moderate chronic hepatitis and 25% had mild hepatitis. 13 (46.4%) had G1 hepatitis, 10 (35.7%) had G2 hepatitis, 3 (10.8%) had G3 hepatitis and 2 (7.1%) had G4 hepatitis, and serum HBV DNA positive rate was 35.7%. There were no differences in HBV DNA levels between different hepatitis group and fibrosis stage group (P > 0.05). There were no differences in all indexes between HBV DNA negative group and HBV DNA positive group (P > 0.05). There were no differences in all indexes between HBV patients and other patients (P > 0.05). CONCLUSION: Occult HBV infection may account for a high proportion of the cases with chronic hepatitis of unknown etiology. Most patients are chronic mild hepatitis, but they still have HBV replication and can progress to liver cirrhosis. Serum PCR test, liver biopsy and immunohistochemistry are helpful for the diagnosis.

[An analysis of the pathohistology of liver tissues, clinical features and prognostic factors of chronic hepatitis B virus carriers].

OBJECTIVE: To study the correlations between clinical features and liver pathohistological changes of chronic hepatitis B virus (HBV) carriers and to discuss the factors which may influence the prognosis. METHODS: Ninety HBV carriers who had liver biopsies were enrolled in this study. RESULTS: (1) The mean follow-up period of the patients was 118 weeks. (2) Fifty-four patients (60.0%) had G1 hepatitis and 21 (23.3%) had G2 hepatitis. The fibrosis stages were graded as S1(42) and S2(21). (3) There were significant age differences among S0, S1 and S2. (4) There were significant differences in aminotransferase levels between patients who had a normal liver histology and those who had mild hepatitis. (5) The grades of liver inflammation were not correlated with the titers of HBeAg and HBV DNA in sera. The stages of liver fibrosis were not correlated with the titers of HBVDNA in sera. Most of the HBeAg negative patients progressed to S2. (6) There were significant differences in spleen dimensions measured by ultrasonography between S0, S1 and S2 patients. (7) During the follow-up period serum aminotransferase (ALT) levels remained normal in 60 patients (group A); 22 patients had transient elevations (group B), and 8 patients had persistent increases (group C). There were significant differences of the ratios of S0 and S2 cases among patients in groups A, B and C. (8) Age and fibrosis stages were predictive factors of liver cirrhosis. CONCLUSIONS: Most chronic HBV carriers had mild inflammatory histological changes in their livers and also had different degrees of liver fibrosis. This follow-up study shows that some of those carriers should have had antiviral therapy.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting.

AIM: To assess the efficacy and safety of combined directly acting antivirals (DAAs) for the treatment of Chinese chronic hepatitis C (CHC) patients in a real-world setting. METHODS: Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS: Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3% (45/54) achieved rapid virological response at 2 wk after treatment initiation (RVR 2) and 94.4% (51/54) achieved sustained virological response at 24 wk after the end of treatment (SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels (83.6 ± 17.9 vs 88.8 ± 19.4, P01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P01 < 0.001), and no significant improvements were observed at 24w after the end of treatment (83.6 ± 17.9 vs 86.8 ± 19.1, P02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P02 = 0.001). The total frequency of adverse events (AEs) during treatment was 33.3% (18/54), with major AEs being fatigue (16.7%), headache (7.4%), anorexia (7.4%), and insomnia (5.6%). CONCLUSION: Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.

[Serum autoantibodies of patients with chronic hepatitis C and the significance thereof in infection of hepatitis C virus].

OBJECTIVE: To investigate the serum autoantibodies in patients with chronic hepatitis C and to investigate the significance of autoimmune reaction in hepatitis C virus (HCV) infected patients. METHODS: Peripheral blood samples were collected from 69 patients with chronic hepatitis C, 69 patients with chronic hepatitis B (HB), and 69 patients with autoimmune hepatitis (AIH). Indirect immunofluorescence technique was used to detect the serum anti nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (anti-SMA), and anti-liver-kidney antibody (anti-LKM). HCV RNA was detected by PCR. The biochemical indices: alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and gamma-globulin were detected. The relations of autoantibodies to virus load, HCV genotype, cirrhosis, age, sex, and liver function were analyzed. RESULTS: (1) Twenty of the HCV patients were positive in autoantibodies, most being at a low titer, 11 of them being positive in ANA, 7 in anti-SMA, 1 in anti-AMA, and 1 in anti-LKM, with a positive rate of 28.9%, significantly higher than that of the HB patients (4.3%, P < 0.05), and significantly lower than that of the AIH patients (100%, P < 0.05). (2) There were no significant differences between the autoantibody positive group and autoantibody negative group in virus load and HCV genotype. (3) Fourteen of the 18 patients positive in autoantibodies responded to the anti-virus treatment with alpha-interferon with a response rate of 77.8%, significantly higher than that of the autoantibody negative group (53%, P < 0.05). (4) The average age of the autoantibody positive group was 47 +/- 18 years, significantly higher than that of the autoantibody negative group (39 +/- 12 years, P < 0.05). The positive autoantibody rate of the patients aged >or= 40 was 23.1%, significantly higher than that of the patients aged < 40 (5.8%, P < 0.05). There was no significant difference in the autoantibody rate between males and females. (5) The cirrhosis prevalence rate of the autoantibody positive group was 80%, significantly higher than that of the autoantibody negative group (46.9%, P < 0.05). (6) The serum ALT, AST, TBIL and gamma-globulin of the autoantibody positive group were 191 U/L +/- 89 U/L, 169 U/L +/- 80 U/L, 78 micromol/L +/- 50 micromol/L, and 200 g/L +/- 80 g/L respectively, all significantly higher than those of the autoantibody negative group (113 U/L +/- 69 U/L, 98 U/L +/- 62 U/L, 51 micromol/L +/- 30 micromol/L, and 160 g/L +/- 70 g/L respectively, all P < 0.05). (7) There were no significant differences in HCV RNA load and HCV genotype between the autoantibody positive group and the autoantibody negative group (both P > 0.05). CONCLUSION: HCV infection induces the autoimmune reaction resulting in production of autoantibodies. Positive autoantibody rate is related with cirrhosis and age. Titer and type of autoantibody serve as important indices in the diagnosis and treatment of HCV.

Microwave-assisted enzyme-catalyzed reactions in various solvent systems.

The work describes the accelerated enzymatic digestion of several proteins in various solvent systems under microwave irradiation. The tryptic fragments of the proteins were analyzed by matrix-assisted laser desorption/ionization mass spectrometry. Under the influence of rapid microwave heating, these enzymatic reactions can proceed in a solvent such as chloroform, which, under traditional digestion conditions, renders the enzyme inactive. The digestion efficiencies and sequence coverages were increased when the trypsin digestions occurred in acetonitrile-, methanol- and chloroform-containing solutions that were heated under microwave irradiation for 10 min using a commercial microwave applicator. The percentage of the protein digested under microwave irradiation increased with the relative acetonitrile content, but decreased as the methanol content was increased. These observations suggest that acetonitrile does not deactivate the enzyme during the irradiation period; in contrast, methanol does deactivate it. In all cases, the digestion efficiencies under microwave irradiation exceed those under conventional conditions.

[Clinical and pathological analysis of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome].

OBJECTIVE: To explore clinical and histopathological characteristics of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. METHODS: Clinical data and pathological findings of 10 patients were reviewed. RESULTS: Serum glutamine transpeptidase,alkaline phosphatase levels,alanine transaminase, aspartate transaminase, serum IgG and IgM were elevated in all the patients. They were all positive for anti-mitochondrial antibody and AMA-M2. Nine patients were positive for anti-nuclear antibody and one patient was positive for anti liver-kidney microsome antibody. Liver biopsies in these patients revealed: ten patients had bile duct lesion,hepatitis activities ranged from moderate to severe, and fibrosis ranged from S1 to S3. CONCLUSION: PBC-AIH overlap syndrome is mostly found in middle-aged women. It has the clinical and histopathological characteristics of both PBC and AIH. Accurate and prompt diagnosis of overlap syndrome patients should be based on the clinical presentation,biochemical and immune indexes,and hepatic pathological changes.

Cryoglobulinemia is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients.

BACKGROUND: Mixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin. METHODS: This is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV) RNA levels were checked before treatment, during the fourth and 12th week of treatment, and during the 24th week after cessation of treatment. The genotype of HCV was determined at baseline. Logistic regression analysis was used to assess the factors associated with sustained virological response. RESULTS: Twenty-five patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral treatment, sustained virological response achievement in MC(+) patients was significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001). Univariate Logistic regression analysis and multivariate Logistic regression analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002) was negatively associated with sustained virological response achievement. CONCLUSION: MC is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients treated with pegylated interferon alpha-2a and ribavirin.

Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at least 60 years with chronic hepatitis C.

BACKGROUND: In China, patients with hepatitis C virus (HCV)-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of the combination therapy in the elderly patients. METHODS: Sixty-eight chronic hepatitis C patients, who received the combination therapy, were classified into two age groups: elderly group ((3)60 years, n = 25) and non-elderly group (< 60 years, n = 43). Rapid virological response, complete early virological response, sustained virological response, relapse, non-response rate, and safety were compared between the elderly group and non-elderly group. RESULTS: Overall sustained virological response was lower in the elderly group than non-elderly group (44% vs. 75%, P = 0.012, OR = 0.270, and 95%CI 0.095 - 0.768). Among patients with HCV genotype 1, sustained virological response was lower in the elderly group than non-elderly group (45% vs. 77%, P = 0.015, OR = 0.247, 95%CI 0.078 - 0.781). The proportions of dose reduction due to laboratory abnormalities were significantly higher in the elderly group than non-elderly group (60.0% vs. 32.6%, P = 0.027). Multiple binary Logistic regression analysis confirmed that patient age was an associated factor for sustained virological response. CONCLUSION: Among patients with HCV genotype 1, the elderly patients had lower sustained virological response than non-elderly patients during pegylated interferon-alpha-2a plus ribavirin combination therapy.