Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.

It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.

Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study.

The present study was designed to determine the seroprevalence of hepatitis B and C virus (HBV, HCV) infections and risk factors in the Turkish general population. Participants were enrolled from urban and rural areas of the predetermined 23 EUROSTAT NUTS 2 region. A two-stage stratified sampling method was used to select participants from these regions (n = 5460; 50.9% females; mean (SD) age: 40.8 (14.7) years). Sociodemographics, clinical characteristics and risk factors were recorded at home visits. The seropositivity rates for hepatitis B surface antigen (HBsAg), anti-HCV, anti-HBs and anti-HBc total were 4.0%, 1.0%, 31.9% and 30.6%, respectively. Among HBsAg-positive cases, 94.5% were anti-HBe-positive, 70.2% were HBV-DNA-positive and 2.8% were anti-HDV total positive; 99.1% of HBV infections were of genotype D. Close contact with a hepatitis patient (OR 3.24; 95% CI 2.25-4.66; p < 0.001), living in the southeastern region (OR 2.74; 95% CI 1.7-4.45; p < 0.001), male gender (OR 1.77; 95% CI 1.28-2.46; p < 0.001), being married (OR 1.62; 95% CI 1.02-2.57; p 0.038), educational level less than high school (OR 1.53; 95% CI 1.04-2.26; p 0.03), orodental interventions (OR 1.54; 95% CI 1.01-2.35; p 0.047) and a history of non-disposable syringe use (OR 1.4; 95% CI 1.01-1.96; p 0.045) were significant determinants of HBsAg positivity. Age ≥50 years (OR 2; 95% CI 1.09-4.3; p 0.026) was the only significant predictor of anti-HCV positivity. In conclusion, our findings revealed an HBsAg positivity in 4% and anti-HCV positivity in 1% of the adult population and at least one-third of the population has been exposed to HBV infection in Turkey.

Long-term entecavir or tenofovir disoproxil fumarate therapy in treatment-naïve chronic hepatitis B patients in the real-world setting.

The aim of this study was to determine the long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the natural course of disease in chronic hepatitis B patients (CHB) with/without cirrhosis in clinical practice. A total of 355 treatment-naïve CHB patients were enrolled into the study. The primary outcome measure was viral suppression as defined by serum HBV DNA level <20 IU/mL. A secondary outcome measure was to determine the development of Hepatocellular carcinoma (HCC). Virological and biochemical responses were similar between the two treatment groups over time. The presence of cirrhosis and hepatitis B e antigen (HBeAg) positivity did not appear to impact viral suppression. The cumulative probability of HBeAg loss was 41% at 4 years of therapy. Hepatitis B surface antigen (HBsAg) loss occurred in four patients. Model for End-Stage Liver Disease score was significantly improved from baseline to week 48 and 96 under antiviral therapy (P = 0.013, P = 0.01). HCC was diagnosed in 17 patients (4.8%). The cumulative probability of the development of HCC was 3.3% at 1 year and 7.3% at 4 years of therapy. The development of HCC was independently associated with older age (P = 0.031) and the presence of cirrhosis (P = 0.004). Serum creatinine levels and creatinine clearance remained stable over time. ETV and TDF effectively maintained virological and biochemical responses in long-term follow-up of CHB patients with/without cirrhosis. HCC may still develop, although at a lower rate, and is more likely to develop in patients with cirrhosis, especially in older patients.

Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B.

BACKGROUND: Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients. AIM: To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients. METHODS: We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA <2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped. RESULTS: Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA <2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA <2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response. CONCLUSION: In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Loss of intrahepatic HBsAg expression predicts sustained response to peginterferon and is reflected by pronounced serum HBsAg decline.

There is a lack of knowledge regarding the effect of peginterferon (PEG-IFN) on the expression of intrahepatic hepatitis B core and surface antigen (HBcAg and HBsAg) in chronic hepatitis B (CHB) and its relation with response to therapy. Fifty-two HBeAg-positive and 67 HBeAg-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG-IFN therapy were studied. After PEG-IFN therapy, HBeAg-negative patients showed a significant reduction in both intrahepatic HBcAg (P = 0.04) and HBsAg expression (P < 0.001). In contrast, a reduction in intrahepatic HBcAg expression was not observed in HBeAg-positive patients, while a trend in reduction of intrahepatic HBsAg staining was found (P = 0.09). Post-treatment, 7 (13%) HBeAg-positive and 9 (14%) HBeAg-negative patients had no expression of intrahepatic HBsAg. Patients without any intrahepatic HBsAg expression post-treatment were more likely to achieve a combined response (HBeAg loss with hepatitis B virus (HBV) DNA <2000 IU/mL for HBeAg -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBeAg-negative CHB): 71% vs 5% for HBeAg-positive (P < 0.001) and 60% vs 16% for HBeAg-negative patients (P = 0.004), respectively. Moreover, a more profound decline of serum HBsAg was observed in patients with absence of intrahepatic HBsAg staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBeAg-positive and HBeAg-negative CHB, respectively). In conclusion, PEG-IFN reduces expression of intrahepatic HBsAg. Loss of HBsAg as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBsAg decline.

A pilot study: longer duration of posttransplant hepatitis C virus therapy may increase the sustained response rate.

BACKGROUND: Although end of treatment virological responses are similar in posttransplant patients with recurrent chronic hepatitis C virus infection and nontransplant patients, the sustained virological response rate is lower in the posttransplant setting. We investigated the efficacy of a longer duration (3 years) of therapy. METHODS: Thirteen patients with biopsy-proven recurrent hepatitis C were included in the study. In the first year of therapy, all patients were treated with a standard regimen of interferon alpha 2b 3MU 3 times in a week plus ribavirin (800 to 1000 mg/d). After the availability of pegylated interferon, patients were converted to pegylated interferon (1.5 microg/kg body weight). Hepatitis C virus RNA was evaluated at months 3, 6, 9, 12, 24, 36, and 42. If hepatitis C virus RNA was negative at month 12, the patients continued treatment for 36 months. RESULTS: Hepatitis C virus RNA was negative in six patients at 12 months, including two who became hepatitis C virus RNA negative after 3 months; two, after 6 months; and two, after 12 months of therapy. Those six continued treatment completing 3 years of treatment with a sustained virological response. Four of those six patients with sustained virological response required colony-stimulating factors during treatment. CONCLUSION: Although the hepatitis C virus RNA status of patients at 12 weeks is a good marker to predict a sustained virological response in the nontransplant setting, it is not valid in posttransplant patients. A prolonged duration of therapy for patients who are viral responders at 12 months may prevent recurrence and increase the sustained virological response rate.

Safety, tolerability, and efficacy of pegylated-interferon alfa-2a plus ribavirin in HCV-related decompensated cirrhotics.

BACKGROUND: Pretransplantation clearance of hepatitis C virus (HCV)-RNA reduces the risk of HCV recurrence after transplantation. Furthermore, a sustained virological response could reduce disease progression and slow clinical deterioration in nontransplanted patients. AIM: To evaluate the safety, tolerability and efficacy of pegylated-interferon (PEG-IFN) alfa-2a plus ribavirin therapy in HCV-related decompensated cirrhotics. METHODS: Twenty HCV-related decompensated cirrhotics (44-67 years, 12 males, six Child-Pugh score A, 14 Child-Pugh score B, all with genotype 1b) were enrolled into the study. Treatment with PEG-IFN alfa-2a (135 microg, once a week) plus ribavirin (1000-1200 mg/day) was commenced. A 48-week treatment was planned in patients who had early virological response. RESULTS: Treatment was stopped in 8 (40%) patients. The remaining 12 (60%) patients completed 48 weeks of therapy; nine (45%) of them obtained end-of-therapy virological response and six (30%) of them obtained sustained virological response. Living donor liver transplantation was performed in three (15%) patients. Eight (40%) and six (30%) patients needed to reduce PEG-IFN alfa-2a and ribavirin dosages, respectively. No patient died during the follow-up period. CONCLUSION: PEG-IFN alfa-2a plus ribavirin therapy is safe, tolerable and efficacious in selected HCV-related decompensated cirrhotics.

Comparison of sequence analysis and INNO-LiPA HBV DR line probe assay in patients with chronic hepatitis B.

The aim of this study was to compare direct sequence analysis of partial HBV pol gene and Inno-LiPA HBV DR in serum samples of 120 chronic hepatitis B patients sent to the Clinical Microbiology Laboratory of Ege University Hospital because of lamivudine resistance. Sequence analysis was performed on ABI Prism 310 Genetic Analyzer. Comparison of Inno-LiPA and sequence results obtained by double-blind evaluation showed full agreement (both at rt180 and rt204) in 58.8% of samples. Visually rechecking of the electropherograms increased this rate to 68.3% Codon based rates are 81.7% and 75.8% at rt180 and rt204 respectively. LiPA detected variants in additional 12 (10%) samples, but missed one variant sample (both rt180 and rt204) and one sample was indeterminate due to poor probe binding. LiPA allows determination of mixed variants and seems to be more sensitive and simple for routine testing even though sequence analysis is still the gold standard for detecting new variants.

Gastrointestinal effects of selective and non-selective non-steroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed group of drugs. Patients receiving NSAIDs often experience abdominal discomfort, and some of them develop serious gastrointestinal complications, such as ulceration, bleeding, perforation, or obstruction. Gastrointestinal side effects of NSAIDs are mostly attributed to cyclooxygenase (COX) inhibition resulting in reduction of prostaglandin in gastric mucosa. Topical irritant effects are also contributed to their systemic effect of prostaglandin inhibition. Anti-inflammatory effects of NSAIDs are mediated by COX-2 inhibition, while COX-1 inhibition is responsible for gastric prostaglandin inhibition. Management of gastrointestinal complications of NSAIDs is costly. In order to prevent or treat the gastrointestinal complications of NSAIDs, anti-ulcer drugs can be used concomitantly. Other alternative is the application or substitution of COX-2 selective inhibitors, which spare gastric mucosal prostaglandin synthesis and do not damage the gastric mucosa. Application of COX-2 selective inhibitors as a first line treatment for arthritic disorders may not be cost-effective, if patients do not have any risk factors including advanced age, history of complicating peptic ulcer, concomitant anticoagulant and corticosteroid medication. Patients with risk factors or those developing gastrointestinal complications during the course of NSAID treatment can be treated with COX-2 selective inhibitors if necessary.

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

HBV vaccination in liver transplant recipients: not an effective strategy in the prophylaxis of HBV recurrence.

Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent hepatitis B virus (HBV) reinfection after liver transplantation. Although they are very effective, development of mutant viruses and high cost of treatment are main limitations for their application. Additionally there is an uncertainity for the duration of that prophylaxis regimen and its mostly applied indefinitely. Recently, post-transplant HBV vaccination is reported to be a cheaper alternative prophylaksis strategy, that enables discontinuation of HBIG. To investigate the efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we administered double course of double dose recombinant HBV vaccine (Genhavac B; containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started 1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. The first cycle consisted of 0, 1- and 6-month schedule, and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients included into the study. Only one patient seroconverted (an anti-HBs titre of 37 IU/L) after the first cycle. No other patient responded to second cycle. HBV vaccination in the post-transplantation setting does not seems like an effective strategy in the prophylaxis of HBV recurrence.

Impact of pretransplant MELD score on posttransplant outcome in living donor liver transplantation.

It is not clear whether pretransplantation MELD (model for End-Stage Liver Disease) score can foresee posttransplant outcome. We retrospectively evaluated 80 adult patients (55 men, 25 women) who underwent living donor liver transplantation between September 1998 and March 2003. Five other patients with fulminant hepatitis were excluded. The UNOS-modified MELD scores were calculated to stratify patients into three groups: group 1) MELD score less than 15 (n = 13); group 2) MELD score 15 to 24 (n = 36); and group 3) MELD score 25 and higher (n = 26). The patients were predominantly men (n = 52, 69.3%) with overall mean age of 43.9 years (range, 17-62 years). The mean follow-up was 15.7 months (range, 1-47; median = 14 months). The mean MELD score was 22.7 (range, 9-50; median = 21). The overall 1- and 2-year patient survivals were 87% and 78.7%, respectively. The 1-year patient survivals for groups 1, 2, and 3 were 100%, 87%, and 79%; respectively. 2-year survivals, 100%, 79%, and 61%, respectively. Survivals stratified by MELD showed no statistically remarkable differences in 1-year and 2-year patient survival (P = .08). In contrast, 1-year and 2-year patient survival rates for UNOS status 2A, 2B, and 3 were 73%-50%, 95%-91%, and 91%-91%, statistically significant difference (P = .002). Finally, to date preoperative MELD score showed no significant impact on 1- and 2-year posttransplant outcomes in adult-to-adult living donor liver transplantation recipients, but we await longer-term follow-up with greater numbers of patients.

Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey.

The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML), 281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.

Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey

The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6 percent), motility disorder-like (ML), 281 (31.2 percent), and the combination (C) of these symptoms, 298 (33.1 percent). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups