Milton G. Mutchnick

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‐α2b (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.

Portal-Systemic Encephalopathy and Portacaval Anastomosis: A Prospective, Controlled Investigation

Portal-systemic encephalopathy (PSE) is generally considered to be the most common and most serious complication of portacaval anastomosis (PCA). Reports of the frequency of this syndrome vary widely, but the true prevalence is not known. The frequency of PSE was determined in 100 cirrhotic patients who were included in two prospective, randomly controlled investigations of prophylactic PCA—40 patients with patent shunts and 60 unoperated control patients. A second nonrandomized group of 118 patients, 39 with therapeutic PCA and 79 without, was also analyzed, and the findings were similar. PSE occurred in 20% of the patients before their inclusion in the study. After inclusion, during a mean period of follow-up of more than 4 years, 35% of the control patients and 53% of the shunted patients developed PSE, an insignificant difference. Severe, chronic PSE occurred in 20% of the shunted and in only 3% of the unshunted patients (P

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 (

Combination low-dose lymphoblastoid interferon and thymosin α1 therapy in the treatment of chronic hepatitis B

36.00), before vaccination (

Ultrasound diagnosis of fatty liver in patients with chronic liver disease: A retrospective observational study

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 (

An Unusual Case of Amoxicillin/Clavulanic Acid-Related Hepatotoxicity

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 (

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

438.00 for a three injection course).

Defective in vitro gamma interferon production and elevated serum immunoreactive thymosin β4 levels in patients with inflammatory bowel disease

SUMMARY. This open label study was initiated to assess the safety and efficacy of lymphoblastoid interferon‐α (IFN‐α) and thymosin α1 (Tα1) in the treatment of 11 patients with chronic hepatitis B, who had failed to respond to standard IFN‐α2b therapy, and in four interferon naive patients. These fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus (HBV) DNA positive patients were given Tα1 (1 mg) subcutaneously (sc) on 4 consecutive days. Low‐dose lymphoblastoid IFN‐α (3 MU) was administered intramuscularly (IM) on the fourth day. Beginning with the second and for the subsequent 25 weeks, patients self‐administered Tα1 twice weekly in the morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN‐α. Patients were followed‐up for 12 months. Nine (60%) of the 15 patients, including six (55%) of the 11 patients previously treated with IFN‐α2b, responded by losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six of the nine responders seroconverted to HBsAg negativity. Significant improvements in the Knodell histological activity index were observed in the responders and no significant adverse effects were observed. Combination low‐dose lymphoblastoid IFN‐α and Tα1 treatment may provide a safe and potentially effective therapeutic approach in chronic hepatitis B. These results require confirmation in future randomized controlled studies.

MicroELISA method for measurement of human serum thymosin α1

Objectives Hepatic ultrasound (US) is readily available and physicians usually trust the results of an US report suggesting fatty liver, but there are conflicting reports on its accuracy, especially in patients with chronic liver disease (CLD). Therefore, we retrospectively examined liver biopsies in patients with CLD and compared the histologic results to the hepatic US findings. Methods Liver biopsies were graded for fat (grades 0 to 3), inflammation (grades 0 to 4), and fibrosis (stages 0 to 4) in 131 patients with CLD (89% had chronic hepatitis C). Hepatic US interpretations were grouped into 3 categories—“normal,” “fatty liver,” and “nonspecific.” A secondary analysis was performed using 3 sonographic categories based on the echogenicity: normal, “increased echogenicity,” and “heterogenous.” The US results were then compared with the liver biopsy results. Results A normal US report was associated with many false negatives, as 25% of these patients had fat (grades 1 to 3) on biopsy; furthermore, 46% had “significant fibrosis” (stages 2 to 4) or “significant inflammation” (grades 2 to 4). A “fatty liver” interpretation correctly identified fat on biopsy in 36.4% and “significant fat” (grades 2 to 3) in 11.4%, but 66% had significant fibrosis or significant inflammation. An US with increased echogenicity correctly identified fat in 43.5% and significant fat in 19.4%, but 69.4% had significant fibrosis or significant inflammation. The sensitivity of an US ranged from 11.4% to 88.2% and the specificity ranged from 40.4% to 86.2%, depending on the degree of steatosis on biopsy and the sonographic interpretation being considered. Conclusions US is inaccurate for diagnosing hepatic steatosis in patients with CLD. Echogenic abnormalities are more likely to be the result of fibrosis or inflammation in this setting.

Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma.

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.