Clinical Characteristics and Treatment Outcome of Peginterferon Plus Ribavirin in Patients Infected with Genotype 6 Hepatitis C Virus in Korea: A Multicenter Study.

BACKGROUND/AIMS: Because of the limited geographic distribution, there have been insufficient data regarding hepatitis C virus (HCV) genotype 6 in Korea. This study aimed to investigate the clinical characteristics and available treatment outcomes of patients with genotype 6 HCV in Korea. METHODS: From 2004 to 2014, data were collected from Korean patients infected with genotype 6 HCV in eight hospitals. RESULTS: Thirty-two patients had genotype 6 HCV. The median age was 44 years, and 6c was the most common subtype. The baseline median alanine transaminase level was 88 (21 to 1,019) IU/mL, and the HCV RNA level was 1,405,000 (96,500 to 28,844,529) IU/mL. Twenty-five patients were treated with peginterferon (PEG-IFN) and ribavirin. Three follow-up losses occurred. Additionally, 13 patients attained a sustained virologic response (SVR), seven patients relapsed, and two patients exhibited a null response. The SVR rates were 40% and 75% for the 24- and more than 48-week treatments, respectively, and five of the six patients who achieved a rapid virologic response (RVR) attained a SVR. CONCLUSIONS: Korean patients infected with genotype 6 HCV are relatively young, and 6c is the most common subtype. When treated with PEG-IFN and ribavirin, the SVR rate was 52%. Similar to other genotypes, a longer duration of treatment and attainment of RVR are important for SVR.

The effect of early goal-directed therapy for treatment of severe sepsis or septic shock: A systemic review and meta-analysis.

PURPOSE: To assess the effects of early goal-directed therapy (EGDT) on reducing mortality compared with conventional management of severe sepsis or septic shock. MATERIALS AND METHODS: We included a systemic review, using the Medline and EMBASE. Seventeen randomized trials with 5765 patients comparing EGDT with usual care were included. RESULTS: There were no significant differences in mortality between EGDT and control groups (relative risk [RR], 0.89; 95% confidence interval [CI], 0.79-1.00), with moderate heterogeneity (I2=56%). The EGDT was associated with lower mortality rates when the mortality rate of the usual care group was greater than 30% (12 trials; RR, 0.83; 95% CI, 0.72-0.96), but not when the mortality rate in the usual care group was less than 30% (5 trials; RR, 1.03; 95% CI, 0.92-1.16). The mortality benefit was seen only in subgroup of population analyzed between publication of the 2004 and 2012 Surviving Sepsis Campaign guidelines, but not before and after these publications. CONCLUSION: This meta-analysis was heavily influenced by the recent addition of the trio of trials published after 2014. The results of the recent trio of trials may be biased due to methodological issues. This includes lack of blinding by incorporating similar diagnostic and therapeutic interventions as the original EGDT trial.

Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery.

The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

Effect of Coffee Added to a Polyethylene glycol plus Ascorbic acid Solution for Bowel Preparation prior to Colonoscopy.

BACKGROUND AND AIMS: Conventional bowel cleansers for colonoscopy have an unpleasant taste and a large volume of solution must be ingested. Coffee increases bowel motility and has an intense flavor. The addition of coffee to a polyethylene glycol+ascorbic acid solution reduces the volume of the solution to be consumed without reducing efficacy, improves the taste of the solution and enhances patient comfort. METHODS: Outpatients with clinical indication or people who wanted screening for cancer were considered eligible. Control group (PEGAS group) consumed a 1-L solution of polyethylene glycol+ascorbic acid twice. Study group (COF group) consumed 750 mL of coffee+polyethylene glycol+ascorbic acid twice. Bowel cleansing was rated using the Aronchick, Ottawa scale, polyp detection rate and colonoscopic insertion time. Tolerability, acceptability, preference, and adverse events were investigated by questionnaires. RESULTS: The COF group had non-inferiority in efficacy (non-inferiority margin, -15%; lower limit of 95% confidence interval for difference between success rates, -4.7% and -8.4% from both scales, respectively). Polyp detection rates were 0.48 and 0.60, respectively (P=0.067). Colonoscopic insertion times were 323.6+/-166.8 s and 330.7+/-243.6 s, respectively (P=0.831). Significant improvement was observed with respect to ease of drinking (P=0.012), taste (P=0.026) and preference (P=0.046) in the COF group. Adverse events occurred in 52.4% and 60.4% in the two groups, respectively (P = 0.251). CONCLUSION: The addition of coffee to polyethylene glycol+ascorbic acid solution reduces the required volume for bowel preparation without reduced efficacy and enhances patient comfort in coffee-drinkers.

Transenteral bowel preparation for colonoscopy is more comfortable than the traditional method with no inferiority in efficacy.

BACKGROUND: Transenteral (TE) administration of a bowel cleanser prior to colonoscopy avoids the discomfort associated with drinking a large volume of unpalatable cleanser. AIM: To explore patient comfort, preference for future colonoscopy, the efficacy and adverse events associated with TE bowel preparation. METHODS: Bowel preparation is traditionally practised using polyethylene glycol (PEG) + ascorbic acid (ASC), which was the treatment used in the control group (peroral group; PO group). In the study group (TE group), PEG + ASC were administered directly to the third portion of the duodenum through a scope immediately after completing upper gastrointestinal endoscopy. RESULTS: A higher proportion of subjects in the TE group graded their degree of comfort as very or rather comfortable (28.4 % in the PO group, 65.1 % in the TE group; p = 0.000) and had greater preference for future colonoscopy (69.6 % in the PO group, 82.5 % in the TE group; p = 0.030), compared with the PO group. The TE group had non-inferiority in efficacy compared with the PO group (non-inferiority margin -15 %; lower limit of 95 % confidence interval for difference between success rates -6.4 %, when using the Aronchick Scale, and -7.1 % when using the Ottawa Scale). Nausea or vomiting were more prevalent during preparation in the PO group (46.1 vs. 17.5 %; p = 0.000), and dizziness was more common in the TE group (0 vs. 12.6 %; p = 0.000). CONCLUSIONS: TE preparation was found to be more comfortable than the traditional peroral method and not inferior in efficacy. The adverse events rate was acceptable.

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study.

BACKGROUND AND AIM: As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea. METHODS: A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009. RESULTS: The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively. CONCLUSIONS: Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.

A comparison of clevudine and entecavir for treatment-naïve patients with chronic hepatitis B: results after 2 years of treatment.

BACKGROUND: This study was undertaken to compare the efficacy, safety, and resistance profile of clevudine (CLV) and entecavir (ETV) following a 2-year treatment period. METHODS: One hundred and eight Korean patients from the prior 48-week study were followed with continuous therapy for up to 2 years and monitored for hepatitis B virus (HBV) DNA levels, HBeAg seroconversion, serum ALT, emergence of drug-resistant mutant HBV, and drug-related adverse events. RESULTS: A complete virological response during the 2-year treatment period occurred in 68.0 % in the CLV group and in 84.5 % in the ETV group (p = 0.043). The cumulative percentage of patients with sustained virological responses at 2 years was 54.0 and 77.6 % in the CLV and ETV group, respectively (p = 0.010). Virological breakthrough occurred in 12 patients in the CLV group; however, there were none in the ETV group (p < 0.001). HBeAg seroconversion rates were not different between the two groups. In patients who maintained sustained virological responses at 2 years, the mean reduction in HBsAg titer was -0.24 and -0.06 log IU/ml in the CLV and ETV group, respectively (p > 0.05). Clinical myopathy occurred in seven patients in the CLV group; however, this was not observed in the ETV group (p = 0.004). CONCLUSIONS: ETV was associated with a significantly higher virological response rate than CLV at 2 years. ETV was superior to CLV in terms of the drug resistance profile and the development of clinical myopathy. Further studies to see whether the unique characteristic of CLV to reduce HBsAg titer is associated with the removal of ccc-DNA from hepatocytes and the remission of the disease are needed.

Clinical characteristics of patients with Mycoplasma pneumoniae-related acute hepatitis.

BACKGROUND/AIMS: Although the hepatobiliary manifestations of Mycoplasma pneumoniae infection have been described in several previous studies, controversies still remain. The aim of this study was to evaluate the clinical characteristics of patients with M. pneumoniae-related hepatitis and compare to those with M. pneumoniae infection but not hepatitis. METHODS: We reviewed the medical chart of patients diagnosed with M. pneumoniae infection serologically. RESULTS: Among the 117 patients with M. pneumoniae infection enrolled in the study, 25 showed acute hepatitis without any evidence of another cause. Patients with hepatitis presented with prodromal symptoms more frequently and also had a higher body temperature and C-reactive protein (CRP) levels than patients without hepatitis. Frequencies of respiratory tract involvement were not different between two groups. Clinical signs recovered within three weeks in both groups following the institution of antibiotic therapy. Multivariate analysis revealed that male sex, age <40 years, and high CRP levels were significantly linked to M. pneumoniae-related hepatitis. CONCLUSIONS: We found that acute hepatitis associated with M. pneumoniae occurred in about 21% of all M. pneumoniae infections, and gender, age, and CRP levels were factors related to the occurrence of M. pneumoniae-related hepatitis.

A case of intraperitoneal immunoglobulin G4-related inflammatory pseudotumor.

The term inflammatory pseudotumor (IPT) has been used to describe inflammatory and fibrosing tumoral processes of an undetermined cause that may involve a variety of organ system. IgG4-related disease is a newly recognized fibroinflammatory condition characterized by IgG4-producing plasma cell expansion in affected organs and, often but not always, elevated serum IgG4 concentrations. IgG4-related IPTs, a subtype of IPT, are characterized by dense infiltration of IgG4-positive plasma cells and stromal fibrosis. The association between inflammatory pseudotumor and IgG4 was first reported with a regard to sclerosing pancreatitis. Despite there are many reports on intraperitoneal IPTs including both cellular and lymphoplasmacytic type, only a few cases have been confirmed to be IgG4-related. We experienced a case of intraperitoneal IgG4-related inflammatory pseudotumor in an 83-year-old woman presenting with epigastric pain and malaise. Surgical specimens revealed an IgG4-related inflammatory pseudotumor.

A case of breast cancer in a male patient with cryptogenic cirrhosis.

Breast cancer is a rare disease in men. We report a case of 53-year-old obese male, with known cryptogenic cirrhosis and hepatocellular carcinoma, presenting a tender mass on left breast. He was diagnosed with invasive intraductal carcinoma, which was consistent with a sporadic lesion. On the basis of previous literatures, obesity can be regarded as a cause for breast cancer even in men. However, there has been inconsistent data about link between liver cirrhosis and male breast cancer, which can be due to heterogenity in the etiology of cirrhosis. Through this case, it can be postulated that the risk for male breast cancer may vary according to the etiology of cirrhosis.

Prevalence of minimal change lesions in patients with non-erosive reflux disease: a case-control study.

BACKGROUND/AIMS: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). METHODS: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). RESULTS: Overall frequency of MC (≥ 1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72-9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. CONCLUSIONS: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

A case of nonpolypoid cancer arising from colonic muco-submucosal elongated polyp.

A colonic muco-submucosal elongated polyp (CMSEP) was identified at colonoscopy in a 53-year-old male patient with lower gastrointestinal bleeding. Non-polypoid depressed type of early cancer was noted at the tip of the colonic polyp. The CMSEP is very rare and incidentally found in most cases. Moreover, its association with colonic neoplasia is extremely rare. To our knowledge, this is the second case report of CMSEP associated with a cancerous transformation.

A Case of Small Bowel Ulcer Associated with Helicobacter pylori.

The etiology of peptic ulcer disease in children may be primary, associated with Helicobacter pylori infection, or secondary, relied on underlying disease. Ulcerative lesions by H. pylori are mainly distributed in the duodenal bulb and they are rare below the ampulla of Vater because H. pylori growth is inhibited by bile juice. In this reason, there are only some restrictive reports presented small bowel ulcer associated H. pylori. We found multiple small bowel ulcerative lesions associated with H. pylori in an 11-year-old girl without any systemic disease while performing esophagogastroenteroscopy to the level of the proximal jejunum for differentiating bezoar. The abdominal pain improved after the patient was administered H. pylori eradication therapy. Because a small bowel ulcer associated with H. pylori has rarely been reported, we report it here with literature review.

Ribavirin dose and treatment outcome of Korean patients with genotype 1 chronic hepatitis C.

BACKGROUND/AIMS: The current recommendation of ribavirin dose for the treatment of chronic hepatitis C is based on study results of Western patients, and might not be optimal for Korean patients because of different body frames. METHODOLOGY: A total of 163 treatment-naive genotype 1 chronic hepatitis C patients who received combination therapy with pegylated interferon a-2a and ribavirin were reviewed. RESULTS: Under current ribavirin dosing, only 49% of patients started therapy with ribavirin dose of 13-15mg/kg (targeted dose), while 45% and 6% of patients started therapy with ribavirin dose =16mg/kg and <13mg/kg, respectively. Patients who started therapy with higher ribavirin dose experienced more ribavirin dose modification during treatment (55%, 31% and 11% for ribavirin dose of =16mg/kg, 13-15mg/kg and <13mg/kg, respectively, p=0.002). The sustained virological response (SVR) rate was 66%, 63% and 56% for ribavirin dose of =16mg/kg, 13-15mg/kg and <13mg/kg, respectively (p=0.775). CONCLUSIONS: A certain proportion of Korean patients started therapy with a higher than targeted ribavirin dose, which resulted in more ribavirin dose modifications without definite additional benefit in achieving SVR. Therefore, the ribavirin dosing regimen might need to be reassessed.

Jejunocolic fistula associated with an intestinal T cell lymphoma.

Malignant fistula of the small bowel to the colon is rare and is most often due to adenocarcinoma. Small bowel lymphoma is unusual, representing less than 1 percent of all gastrointestinal malignancies. We report a case of intestinal lymphoma presenting with diarrhea and abdominal pain. A jejunocolic fistula was discovered during colonoscopy. Celiotomy revealed a large, ulcerated fistula tract between the jejunum and distal transverse colon, and pathology was consistent with peripheral T-cell lymphoma. This is a rare entity in a nonimmunocompromised individual and has not been previously described in Korea.

Antiviral therapy in patients after treatment for hepatitis C-related hepatocellular carcinoma.

BACKGROUND/AIMS: Despite great progress, antiviral treatment for chronic hepatitis C in patients with prior hepatocellular carcinoma (HCC) has been rarely investigated. We evaluated the efficacy and safety of antiviral therapy following treatment for hepatitis C-related HCC. METHODS: Thirteen patients (age 34 to 60 years) who were treated with peginterferon plus ribavirin after treatment for HCC were reviewed. RESULTS: There were 6 patients with genotype 1 and 7 patients with genotype 2. All patients showed advanced fibrosis (≥F3) but belonged to the Child-Pugh class A. Treatment was stopped in 2 patients because of recurrent HCC and in 1 patient due to a lack of early virologic response. Seven patients achieved sustained virologic response and three patients relapsed. The sustained virologic response rate was 54% overall, 17% in genotype 1, and 86% in genotype 2. No significant adverse events were reported. CONCLUSIONS: Antiviral therapy should not be excluded in patients who were previously treated with HCC with genotype 2 chronic hepatitis C, in which an efficacious antiviral treatment for chronic hepatitis C was feasible. Additional study is needed to prove the validity of antiviral therapy in patients with genotype 1 hepatitis C-related HCC.

A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-naïve patients with chronic hepatitis B.

PURPOSE: Clevudine and entecavir are currently available in Korea as antiviral drugs against chronic hepatitis B (CHB). We aimed to compare the efficacy of clevudine and entecavir therapy. METHODS: Treatment-naïve CHB patients who received 30 mg of clevudine or 0.5 mg of entecavir a day were analyzed. Mean reduction of hepatitis B virus (HBV) DNA levels, complete virological response (cVR, undetectable HBV DNA by real-time PCR), biochemical response (recovery to normal ALT level), and hepatitis B e antigen (HBeAg) seroconversion rate at the 48th week of treatment were assessed. RESULTS: A number of 59 patients in clevudine group and 61 patients in entecavir group were included. Mean HBV DNA reductions from baseline were similar in the clevudine and entecavir groups, -6.4 versus -6.8 log(10) copies/mL in HBeAg-positive (p = 0.417) and -6.9 versus -7.0 log(10) copies/mL in HBeAg-negative patients (p = 0.640). The proportion of patients who achieved cVR was not different between the two groups, 53 versus 55% in HBeAg-positive (p = 1.000) and 100 versus 95% in HBeAg-negative patients (p = 0.452). Biochemical response rates and HBeAg seroconversion rates were also similar in both the groups. Two (3.4%) patients in clevudine group showed virologic breakthrough with rtM204I mutation using direct sequencing analysis. Clinical myopathy occurred in two (3.4%) patients in clevudine group. CONCLUSION: Mean reduction of viral loads was similar between clevudine and entecavir groups during 48 weeks. However, virologic breakthrough and significant myopathy were noted only in clevudine-treated patients. Therefore, more attention should be paid to patients receiving clevudine.

Efficacy of peg-interferon-α-2a plus ribavirin for patients aged 60 years and older with chronic hepatitis C in Korea.

BACKGROUND AND AIM: In the present study, we evaluated the safety and efficacy of combination therapy with pegylated interferon and ribavirin for treating chronic hepatitis C (CHC) patients aged 60 years and older. METHODS: A total of 314 CHC patients, who were treated with combination therapy, were classified into three groups according to age: (i) younger than 50 years (n = 137); (ii) 50-59 years (n = 109); and (iii) 60 years or older (n = 68). The sustained virological response (SVR) and discontinuation rates were compared between the three groups. RESULTS: Discontinuation of therapy due to adverse event was more frequent in the older patient groups: 1%, 5%, and 10% for the < 50-year, the 50-59-year, and the ≥ 60-year patient groups, respectively (P = 0.018). However, the older patient groups showed a SVR rate that was comparable to the SVR rates of the other age groups: 80%, 73%, and 75% for the < 50-year, 50-59-year, and ≥ 60-year- patient groups, respectively (P = 0.420). A multivariate analysis showed that the aspartate aminotransferase : platelet ratio index (APRI) was an independent predictor of an SVR. An SVR was achieved in 95% (19/20) of the elderly patients with an APRI < 0.80. CONCLUSIONS: Although physicians must pay more attention to adverse events in the older patients, combination therapy can be considered for older patients, especially for patients with a low APRI.