Ropeginterferon alfa-2b in patients with genotype 1 chronic hepatitis C: Pharmacokinetics, safety, and preliminary efficacy.

BACKGROUND AND AIM: Ropeginterferon alfa-2b (P1101) is a novel long-acting mono-PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N-terminus, allowing every-two-week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa-2b as compared with PEG-IFN-α2a in patients with chronic hepatitis C virus genotype 1 infection. METHODS: One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG-IFN-α2a 180 µg (group 1), weekly ropeginterferon alfa-2b 180 µg (group 2), weekly ropeginterferon alfa-2b 270 µg (group 3), or biweekly ropeginterferon alfa-2b 450 µg (group 4) plus ribavirin for 48 weeks. RESULTS: After multiple weekly administration, serum exposure (AUC0-τ) in ropeginterferon alfa-2b 180 µg was approximately 41% greater and the accumulation ratio of 2-fold greater than PEG-IFN-α2a 180 µg. The incidences of flu-like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1-4, respectively. Two grade 2 of 3 depression were noted in PEG-IFN-α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively. CONCLUSIONS: Ropeginterferon alfa-2b showed longer effective half-life and superior safety profile than PEG-IFN-α2a. Biweekly injection of ropeginterferon alfa-2b will be studied in larger viral hepatitis patient population.

Ropeginterferon Alfa-2b administered every two weeks for patients with genotype 2 chronic hepatitis C.

BACKGROUND: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. METHODS: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg-IFN-α2a) at 180 µg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 µg (n = 23), 360 µg (n = 21), 450 µg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). RESULTS: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg-IFN-α2a 180 µg, Ropeginterferon alfa-2b 270 µg, 360 µg, and 450 µg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. CONCLUSION: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg-IFN-α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Clinical utility of electrogastrography and the water load test in patients with upper gastrointestinal symptoms.

We assessed gastric myoelectric functioning in patients with various gastrointestinal symptoms and to determine the utility of electrogastrography in differentiating specific disease entities. Electrogastrography with a water load was performed in 101 patients with reflux disease, 55 patients with active gastric ulcer, 59 patients with functional dyspepsia, and 30 controls. Upper gastrointestinal symptoms were assessed in each patient. Electrogastrography was abnormal in 41 (40.6%) patients with reflux disease, 31 (56.4%) patients with active gastric ulcer, and 26 (44.1%) patients with functional dyspepsia (P=NS). Water load tolerance was greater in controls than any patient group (all P<0.05). Symptoms predicted abnormal electrogastrography in reflux patents with satiety (OR=2.9; P<0.05) and in dyspeptic patients with nausea (OR=3.1; P<0.05). Although electrogastrography is helpful in differentiating subgroups of patients with nausea or satiety, it cannot directly differentiate disease states such as reflux disease, gastric ulcer, and functional dyspepsia.

Utility of electrogastrography in differentiating Parkinson's disease with or without gastrointestinal symptoms: a prospective controlled study.

BACKGROUND/AIMS: Parkinson's disease (PD) may be associated with various gastrointestinal symptoms. This study was designed to assess the gastric myoelectrical functioning in patients with PD and in healthy controls by using electrogastrography (EGG) with the water load test and to determine the clinical utility of EGG in differentiating PD patients with or without upper gastrointestinal symptoms. METHODS: Twenty patients (13 men, mean age 63 years) with PD and 11 healthy controls (5 men, mean age 55 years) were studied. The PD patients were stratified into two subgroups: 9 were assessed as PD without upper gastrointestinal symptoms (group A) and 11 as PD with upper gastrointestinal symptoms (group B). The gastric myoelectrical activity was assessed using cutaneous electrodes to record EGG before and after the subjects ingested water until full. RESULTS: The PD patients drank significantly less water until full as compared with the controls (303 +/- 45 vs. 627 +/- 67 ml, p < 0.05). At baseline, the PD patients had a significantly higher 1.0- to 2.5-cpm activity as compared with the controls (44 +/- 3 vs. 33 +/- 3%, p < 0.05). These differences persisted after ingestion of the water load. The PD patients had a significantly lower 2.5- to 3.75-cpm activity late after ingestion of the water load as compared with the controls (33 +/- 4 vs. 49 +/- 5%, p < 0.05). No statistically significant differences were found in any EGG variables or the water load between the two groups of PD patients. CONCLUSIONS: This study has shown that the gastric myoelectrical activity is impaired in both groups of PD patients. EGG appears to have a limited, if any, clinical utility in the differentiation of PD patients with or without upper gastrointestinal symptoms.

Electrogastrography differentiates reflux disease with or without dyspeptic symptoms.

Many patients with gastroesophgeal reflux disease (GERD) may also have overlapping symptoms of dyspepsia. This study was to examine if GERD patients could be separated into meaningful groups based on their gastric myoelectrical characteristics. The study included 20 GERD patients with dyspeptc symptoms (GERD+) and 17 patients with GERD. Gastric myoelectrical activity was assessed using cutaneous electrodes to record electrogastrograms (EGGs). The GERD+ patients ingested smaller volumes of water compared to patients with GERD (P < 0.05). At baseline, the percentage of gastric myoelectrical power in the normal 3-cpm range was significantly less in patients with GERD+ compared with the GERD subjects (P = 0.01). Power in the bradygastria range was significantly greater in patients with GERD+ (P = 0.005). The GERD+ group had a significant increase in the percentage of power in the tachygastria range later after ingesting the water load (P < 0.01). In conclusion, this study has shown that more gastric dysrhythmias were detected in the GERD+ patients accompanied with altered perception of stomach fullness.

Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with hepatocellular carcinoma.

BACKGROUND/AIMS: Familial clustering of hepatitis B virus (HBV) infection is related to perinatal transmission, and is the main cause of familial-type hepatocellular carcinoma (HCC). The route of HBV transmission differs between the children and siblings of patients with HCC. This study examined the differences in HBV carrier rates and HCC-related mortality between two generations in HCC families. METHODS: From 1992 to 1997, relatives of individuals with HCC were screened prospectively with ultrasonography, alpha-fetoprotein, liver biochemistry tests and viral markers. Total HCC-related deaths during a 9-year period were compared between the generations of index patients and their children. RESULTS: The study included a total of 13676 relatives in two generations. More HCC-related deaths occurred in the index patient generation than in the child generation. Furthermore, children of female index patients had higher rates of liver cancer related mortality than children of male index patients. The same was true when the analysis was limited to male HBV carriers. The prevalence of HBsAg in the offspring of HBsAg positive mothers was 66% in the child generation and 72% in the index patient generation. These high prevalences indicated high maternal HBV replication status. CONCLUSIONS: Perinatal transmission and maternal viral load are important risk factors in hepatocarcinogenesis.

Eight-year nationwide survival analysis in relatives of patients with hepatocellular carcinoma: role of viral infection.

BACKGROUND: Families of patients with hepatocellular carcinoma (HCC) carry a high risk of developing HCC. We determine the number of fatalities in relatives of HCC patients during an 8-year period to understand the risk and cause of HCC in relatives of patients with HCC. METHODS: From 1992 to 1997, 15 410 relatives of HCC patients in three generations were screened prospectively for HCC by ultrasonography, alpha-fetoprotein, liver biochemistry and viral markers. By using national citizen identification numbers, we searched the total fatalities in relatives of HCC patients between 1992 and 1999 from the national mortality data bank. The results were compared among different viral infection groups. RESULTS: Of the relatives studied, 37.8% were hepatitis B s antigen (HBsAg) positive (+), 4.3% were anti-hepatitis C virus (HCV) (+) and 1.7% were both HBsAg (+) and anti-HCV (+). A total of 399 fatalities, including 139 because of HCC (34.8%), 37 because of liver diseases (9.3%), 88 because of other cancers (22.1%) and 135 because of other diseases (33.8%), were found. Relatives who were HBsAg (+) or anti-HCV (+)showed a lower cumulative survival than did relatives who were negative for both HBsAg and anti-HCV. Relatives with dual infection of hepatitis B and C virus showed the highest mortality due to HCC or terminal liver diseases. CONCLUSIONS: Chronic viral infection rather than a hereditary factor is the main cause of a familial tendency for HCC. Dual infection of hepatitis B and C virus increases the risk of HCC or decompensated liver diseases.

Detection of serologic responses to GB virus C/hepatitis G virus infection.

OBJECTIVES: To investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) and compare the serologic responses to various GBV-C/HGV markers in eastern Taiwan aborigines. METHODS: We used RT-PCR and anti-HGenv u-plate to investigate the prevalence of GBV-C/HGV in eastern Taiwan aborigines. We also used ELISA, dot blot assay, and Western blot to detect the serologic responses to various GBV-C/HGV markers. RESULTS: The prevalence of GBV-C/HGV RNA in the general population of eastern Taiwan aborigines is about 5% (17/317), while 14% (43/317) have anti-E2 antibodies. There were no significant differences in antibody titer against one consensus core peptide (PPSSAAACSRGSPR) between GBV-C/HGV RNA-positive and -negative sera. Only 23 of 42 serum samples positive in the anti-HGenv u-plate EIA assay were positive (55%) in the dot blot assay. No positive signal was detected by Western blot using either recombinant NS3 or commercial E2 proteins. CONCLUSIONS: Antibodies against one consensus core peptide (PPSSAAACSRGSPR) may not constitute a good marker for the detection of GBV-C/HGV viremia. For the detection of anti-E2 antibodies, the anti-HGenv u-plate assay is more sensitive than the dot blot assay. Western blot assay is not a sensitive method for detecting GBV-C/HGV infection.