Racial diversity in mortality and morbidity in urban patients with hepatitis C.

Defining mortality for Caucasians and African American patients with chronic hepatitis C with respect to racial diversity is critical for counselling patients on therapy options. The objective of this study was to define racial diversity influence on mortality and morbidity of 3724 consecutive hepatitis C virus (HCV)-infected patients seen in an urban clinic between 1995 and 2008. Mortality, as of 2011, was defined using the SSA National Death Index and correlated with early visit medical information. The HCV chronically infected patient population consisted of 2879 African Americans (AA), 758 Caucasians and 87 other, and the majority were not treated for their infection prior to 2011. The average time to death from first visit was 5 years, the average age at death was 55 years, and despite racial diversity, AA were just as likely to be reported dead as Caucasians (23% AA vs 22% Caucasians). Cirrhosis and fibrosis (liver biopsy, AST Platelet Ratio Index or Fibrosis-4) at first visit as well as low albumin, diabetes, renal impairment and cardiac symptoms were associated with increased mortality. Treated patients who cleared the virus (sustained viral response (SVR); AA = 59; Caucasians = 40) had lower mortality than patients who were not treated (AA: 5% vs 27%; Caucasians 5% vs 26%). Hence, we find that race is not a factor in the early mortality of patients with chronic HCV infection and achieving a SVR reduced mortality. Unexpectedly, nonresponding AA also benefited by a lower mortality. African American patients with kidney disease and low albumin were at highest risk and should be treated as soon as identified.

A rare cause of dysphagia in a HIV patient--esophageal pseudodiverticulosis.

Esophageal pseudodiverticulosis is a rare clinical entity with a slight male predominance (1). The condition is caused by cystic dilation of the sub mucosal glands and hence is not true diverticulosis. This is usually a benign condition, affecting the distal third of esophagus. It has been associated with reflux esophagitis, strictures and candidiasis. Patients with esophageal pseudodiverticulosis may present with progressive dysphagia, though most cases are asymptomatic. Perforation (2), bleeding (3) and mediastinitis have rarely been described. To the best of our knowledge, the occurrence of this rare disease in HIV patients has been described only once before (4). We report the second case of esophageal pseudodiverticulosis occurring in a HIV patient.

African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians.

African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under-represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end-of-treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon-alpha2b (Intron A) thrice weekly. End-of-treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end-of-treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow-up information. The end-of-treatment response was 7% for patients with genotype 1 and 71% for genotype non-1 (P < 0.005 for genotype non-1). The end-of-treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end-of-treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end-of-treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.

Prevalence of hepatitis A virus and hepatitis B virus immunity in patients with polymerase chain reaction-confirmed hepatitis C: implications for vaccination strategy.

OBJECTIVES: Administration of vaccine for hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for patients with chronic hepatitis C (CHC) because of the potential for increased severity of acute hepatitis superimposed on existing liver disease. The aim of this study is to determine the prevalence of antibodies directed against HAV and HBV in patients with CHC, analyze demographic and risk factors associated with this prevalence, and develop a cost-effective vaccination strategy. METHODS: We reviewed records from 1092 CHC patients. Demographics and information regarding risk factors were obtained by history and questionnaire administered to all patients. The costs of vaccination and antibody testing were determined, based on standard laboratory and clinic charges at our institution. HAV and HBV markers were correlated to race, age, and risk factors. RESULTS: Of the total population studied (n = 1092), 72% were African-Americans, 27% white, and 1% others. Of 671 CHC patients tested for anti-HAV IgG, 252 (38%) were positive. Of 743 CHC patients tested for HBV antibodies (anti-hepatitis B core IgG or anti-hepatitis B surface), 494 (67%) were positive. African-Americans are more likely to have antibodies to HAV and HBV (67% and 75%, respectively) compared to whites (27% and 20%). The prevalence of anti-HAV was 76% in patients >60 yr, 34% in the 40- to 60-yr-old age group, and 21% in patients <40 yr. The highest prevalence of HBV antibodies was found in patients between the ages of 40-60 yr. No HCV risk factors were associated with increased HAV risk. In CHC patients with HBV antibodies, however, illicit injection drug use was the predominant risk factor. CONCLUSIONS: The prevalence of anti-HAV in patients with CHC was found to be similar to that of the general population in the United States (33% according to recent Centers for Disease Control data), consistent with the hypothesis that the two infections do not share risk factors. Because the prevalence of HAV immunity is low in CHC patients <40 yr, empiric HAV vaccination is cost effective. If two doses of vaccine are to be given, however, antibody testing of all HCV patients is indicated. In the subset of patients >60 yr of age or who are African-American, where the prevalence of HAV exposure is considerably higher, it would be cost effective to check the antibody ($36.00), before vaccination ($97.00). The prevalence of HBV antibodies, however, is significantly increased in patients with CHC compared with the general population (5.3% per the Centers for Disease Control), likely as a result of exposure to similar parenteral risk factors. HBV antibody testing ($26.00 per test) should, therefore, be undertaken in all CHC patients who are hepatitis B surface antigen negative, as this approach is cost-effective compared to empiric HBV vaccination ($438.00 for a three injection course).

Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study.

Previous clinical trials have suggested that thymosin alpha1 (Talpha1), an immunomodulatory peptide, may be effective in the treatment of chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of Talpha1 in a multicentre, placebo-controlled and double-blind study of 97 patients with serum hepatitis B virus (HBV) DNA- and hepatitis B e antigen (HBeAg)-positive CHB. Patients who had been hepatitis B surface antigen (HBsAg) positive for at least 12 months entered a 3-month screening period prior to randomization. Forty-nine patients received Talpha1 (1.6 mg) and 48 patients received placebo, twice weekly for 6 months, and were followed-up for an additional 6 months. At inclusion, both groups were comparable for age, gender, histological grading, and aminotransferase and HBV DNA levels. A complete response to treatment, defined as a sustained serum HBV DNA-negative status (two negative results at least 3 months apart) during the 12-month study, with negative HBV DNA and HBeAg values at month 12, was seen in seven (14%) patients given Talpha1 and in two (4%) patients treated with placebo (P = 0.084). Five (10%) patients given Talpha1 and four (8%) patients given placebo exhibited a delayed response (defined as sustained serum HBV DNA negativity achieved after the 12-month study period with negative HBV DNA and HBeAg values at the last assessment). A total of 12 (25%) patients given Talpha1 and six (13%) patients given placebo showed a sustained loss of HBV DNA with a negative HBeAg value during or following the 12-month study period (P < 0.11). These results do not confirm observations of treatment efficacy reported in other clinical studies.

Induction of G(1) checkpoint in the gastric mucosa of aged rats.

Although in Fischer 344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about specific changes in the regulatory mechanisms of this process. To determine whether changes in cell cycling events could partly contribute to the age-related rise in gastric mucosal proliferative activity, the present investigation examines changes in cyclin-dependent kinase (Cdk2) activity and the regulation of this process in the gastric mucosa of Fischer 344 rats aged 4 (young), 13 (middle aged), and 24 (old) mo. We observed that aging is associated with a progressive rise in activity and protein levels of Cdk2 in the gastric mucosa. This is also found to be accompanied by a concomitant increase in cyclin E but not cyclin D1 levels. On the other hand, the levels of p21(Waf1/Cip1) (total as well as the fraction associated with Cdk2), a nuclear protein that is known to inhibit different cyclin-Cdk complexes, are found to decline in the gastric mucosa with advancing age. In contrast, with aging, there was a steady rise in p53 levels in the gastric mucosa. We have also observed that the levels of phosphorylated retinoblastoma protein, a form that participates in regulating progression through the S phase, are markedly elevated in the gastric mucosa of aged rats. In conclusion, our data suggest that, in the gastric mucosa, aging enhances transition of G(1) to S phase as well as progression through the S phase of the cell cycle. However, the age-related decline in p21(Waf1/Cip1) in the gastric mucosa appears to be independent of p53 status.

Efficacy of interferon treatment for patients with chronic hepatitis C: comparison of response in cirrhotics, fibrotics, or nonfibrotics.

Chronic hepatitis C patients (472 patients) were treated with consensus interferon (CIFN) or interferon (IFN) alfa-2b for 6 months in a large multicenter trial. Efficacy was assessed by clearance of hepatitis C virus (HCV) RNA using reverse transcription polymerase chain reaction (RT-PCR) (<100 copies/mL), normalization of serum alanine aminotransferase (ALT), and histological improvement. The purpose of these analyses was to compare these efficacy parameters in nonfibrotics, fibrotics, and cirrhotics. Patients with chronic HCV and cirrhosis showed the same benefit from IFN treatment as noncirrhotic patients when efficacy was assessed by clearance of serum HCV RNA or by histological benefit. Sustained HCV RNA response rates were similar when measured among nonfibrotic (11%), fibrotic (13%), and cirrhotic (11%) patients. Improvement in histologic activity index (HAI) scores was noted among all 3 groups. Cirrhotic patients had a lower sustained ALT response rate (12%) than did nonfibrotic patients (23%). Ninety percent of nonfibrotics, but only 71% of fibrotics and 67% of cirrhotics, who sustained a virological response normalized their ALT. This suggests that cirrhotic patients may clear the hepatitis C virus without normalization of ALT levels. The pattern of both HCV RNA clearance over time and ALT decrease was similar among nonfibrotics, fibrotics, and cirrhotics. Tolerability to IFN therapy was similar among the 3 groups except that more cirrhotics required dose reduction because of thrombocytopenia. In patients with cirrhosis, ALT levels may be a less appropriate endpoint in the measurement of response to therapy. We conclude that liver cirrhosis should not be a reason for excluding patients from therapy because both cirrhotic and fibrotic HCV patients benefit from IFN therapy not only by clearance of virus but by improvements in liver histology.

Aging and cancer of the stomach and colon.

Although the incidence of most human malignancies including cancer of the gastrointestinal tract increases dramatically with advancing age, the precise role of aging in that increase remains a matter of continued controversy. Many probable explanations for the age-related rise in cancer incidence have been offered including altered carcinogen metabolism and the cumulative effects of protracted exposure to cancer-causing agents. Neoplasia of the stomach or colon is a multi-stage process with hyperproliferation being central to the initiation of carcinogenesis. Since aging is associated with increased gastrointestinal mucosal cell proliferation, the possibility that aging itself may render target cells more susceptible to carcinogenic transformation continues to be an area of intense interest and study. This review will examine the evidence for age-related alterations in the structural and functional properties of the gastric and colonic mucosa in an effort to further elucidate the potential mechanisms of carcinogenesis which may be involved during the aging process.

An unusual case of amoxicillin/clavulanic acid-related hepatotoxicity.

Amoxicillin/clavulanic acid is a widely used antibiotic. Hepatic dysfunction is a rare adverse reaction associated with this combination antibiotic. We report the case of a 40-yr-old woman with a somewhat unusual presentation of amoxicillin/clavulanate-related cholestatic hepatotoxicity and multiple duodenal erosions whose diagnosis was delayed until inadvertent rechallenge with the antibiotic combination. The relevant literature is also reviewed and discussed. The diagnosis may be missed because the onset of signs/symptoms may occur several weeks after the cessation of therapy. The hepatic dysfunction, which may be severe and is more prevalent in elderly patients, is usually reversible, although chronic liver disease and deaths have been reported. Immunological hypersensitivity is considered to be the most likely mechanism resulting in liver injury. Amoxicillin/clavulanate should be used with caution in patients with underlying liver disease and in the elderly.

Small bowel obstruction in pregnancy.

OBJECTIVES: Small bowel obstruction (SBO) is an unusual complication of pregnancy. Our objective was to review our experience at two urban hospitals. METHODS: To this end, we conducted a retrospective chart review of all pregnant patients with a discharge diagnosis of intestinal obstruction at Grace Hospital, Detroit, MI (January 1, 1972 to January 1, 1992) and Hutzel Hospital, Detroit, MI (January 1, 1977 to January 1, 1992). RESULTS: During the study period, nine cases of SBO were identified and 150,386 deliveries occurred (one case per 16,709 deliveries). Patients' ages ranged from 16 to 37 yr. There were six primiparas. Cases of SBO by trimester: four in second, four in third, and one in puerperium. Previous abdominal surgery was documented in eight patients. Duration of symptoms before admission ranged from 3 h to 3 days. Primary symptoms were abdominal pain (89%), vomiting (89%), and obstipation (80%). At admission, only one patient was febrile, and four had hypoactive bowel sounds. Abdominal x-rays were compatible with SBO in seven patients. Ultrasound identified SBO in one of four cases. Patients were hospitalized 6 h to 23 days before surgery. The admission diagnosis was incorrect in four cases. One patient was treated conservatively and, at 36 wk, vaginally delivered a healthy infant. The eight surgical patients had lysis of adhesions, with one requiring resection of gangrenous small bowel. There were three fetal deaths (at 22, 24, and 30 wk of gestation). No maternal deaths occurred. CONCLUSION: SBO is a rare, but often catastrophic, complication during pregnancy and the puerperium. Clinical suspicion is critical and should be increased in a patient with an abdominal scar. If suspected, prompt abdominal x-rays, ultrasound, and surgical consultation are warranted.

Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with thymic peptides and antiviral agents.

At the present time, interferon is considered the only effective therapeutic approach in the treatment of both chronic hepatitis B and chronic hepatitis C. It is clear that the disappointing response rates in both chronic hepatitis B and C place added emphasis on efforts to identify alternative forms of therapy. In addition to the development of other antiviral agents including the nucleoside analogs which might prove more effective and have fewer associated side-effects, other agents currently under investigation include thymic peptides such as thymosin alpha 1. In the future, the therapeutic approach to the treatment of chronic hepatitis B and C may consist of combination therapy using perhaps an immune modulator and an antiviral agent or, several antiviral drugs. Alternatively, there is indication that cellular targeting systems with delivery of the toxic material to the specific cell containing the virus may be more effective, while minimizing side-effects. Finally, there are agents such as ursodeoxycholic acid which perhaps, makes bile less toxic and can be used as adjunctive therapy with improvement in liver chemistry values. The treatment of chronic hepatitis B and chronic hepatitis C has shifted in emphasis form the concept of treating liver disease towards that of treating viral infections which happen to effect primarily the liver.

A case of intussusception and lymphoid hyperplasia in a patient with AIDS.

Idiopathic intussusception in adults is rare. In tropical climates, enteric infection is causally implicated. Three cases of intussusception in AIDS patients have been reported, two of which were associated with enteric infection. We report the fourth case of ileocolonic intussusception in an AIDS patient in whom lymphoid hyperplasia of the terminal ileum was found but no infection documented. The relationship between lymphoid hyperplasia and intussusception is discussed. The previous cases of AIDS and intussusception are reviewed. Idiopathic intussusception may become more prevalent as the number of AIDS cases increases, and must be considered in the differential diagnosis of abdominal pain in AIDS patients.

Successful endoscopic injection sclerotherapy of a bleeding duodenal varix.

Bleeding from duodenal varices is an unusual event. We report the case of a 50-yr-old man with portal hypertension due to alcoholic cirrhosis who presented with upper gastrointestinal bleeding and encephalopathy. Emergent endoscopy revealed an actively bleeding duodenal varix. The bleeding was treated successfully with injection sclerotherapy. Only four cases of injection sclerotherapy of bleeding duodenal varices have been reported previously. We review and compare reported cases of sclerotherapy of duodenal varices and also review the other therapeutic options. Endoscopic injection sclerotherapy of bleeding duodenal varices appears to be a useful first-line therapy.

Taurine deficiency after intensive chemotherapy and/or radiation.

Taurine, a nonessential amino acid (AA), is the most abundant free AA in the intracellular space. We measured plasma AA concentrations in 36 patients 7-28 d after intensive chemotherapy and/or radiation. Plasma taurine concentrations were uniformly low in all patients (20.0 +/- 6.4 mumol/L, mean +/- SD). Plasma taurine in 11 healthy volunteer control subjects was 45.0 +/- 20.3 mumol/L (P less than 0.001). Other AA concentrations, specifically those of precursor AAs methionine and cystine, were normal. We prospectively measured plasma AA concentrations in 12 patients before starting and 6-10 d after completing intensive cytotoxic treatment. Values before treatment were 37.2 +/- 11.6, 109.6 +/- 30.7, and 18.5 +/- 4.8 for taurine, cystine, and methionine, respectively, and were 24.3 +/- 6.0, 111.2 +/- 23.8, and 24.0 +/- 14.5 after treatment. Pretreatment plasma taurine correlated directly with the magnitude of decrease in plasma taurine during cytotoxic treatment (n = 12, r = 0.85, P less than 0.01). Intensive cytotoxic chemotherapy and/or radiation leads to a reduction in plasma taurine concentrations without any change in its precursor AAs, methionine and cystine. The clinical relevance of plasma taurine depletion will need further study.

Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis.

To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohn's colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohn's colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohn's than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohn's colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohn's Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohn's colitis.

Candida-associated diarrhea in hospitalized patients.

Ten hospitalized patients with severe diarrhea associated with intestinal Candida overgrowth are reported. Candida-associated diarrhea is predominantly of the secretory type, characterized by frequent watery stools, usually without blood, mucus, tenesmus, or abdominal pain. The patients were elderly, malnourished, and critically ill, or suffered from chronic debilitating illness. Their hospital stays were prolonged, and the majority were being treated with multiple antibiotics or chemotherapeutic agents. Diarrhea often led to dehydration, prerenal azotemia, hyperchloremic metabolic acidosis, and electrolyte imbalance. Stool culture most frequently isolated Cand. albicans in association with decreased normal flora. Colonoscopy showed no evidence of colitis. Diagnosis was made based on the absence of diarrhea-producing medications, the continuation of diarrhea despite fasting, the exclusion of other infections, inflammatory conditions and other causes of secretory diarrhea, and a dramatic response to a short course of nystatin.

Cimetidine-induced galactorrhea.

Various breast abnormalities have been described in patients treated chronically with cimetidine, but galactorrhea has been reported only twice in the medical literature. In both cases, there appeared to be an associated hyperprolactinemia. These problems could well represent a consequence of histamine2-receptor blockade. We report here a female patient with hepatic cirrhosis and portal hypertension who developed hyperprolactinemia and galactorrhea while on long-term cimetidine therapy. Both the hyperprolactinemia and the galactorrhea disappeared when the patient was switched to ranitidine, an alternative H2-receptor blocker. A review of the previous case reports and relevant literature is included.

Clinical features, evaluation, and detection of colorectal cancer.

The most common presentation of colorectal carcinoma is in the symptomatic patient, most often with complaints of rectal bleeding, abdominal pain, or change in bowel habits. Symptomatic patients often have advanced disease and, because surgical resection is the only effective therapy at present, their chance for cure is poor. Until effective treatment is available, therefore, we must identify patients at high risk for lifelong screening. In addition, more effective means of surveillance of the general population need to be developed in order to diagnose patients at risk for sporadic colorectal cancer, given that this represents the majority of patients with disease. Tumor markers also would be useful to find residual disease while it is still resectable in patients who have undergone surgery for curative resection.