Stercorarial shedding and transtadial transmission of hepatitis B virus by common bed bugs (Hemiptera: Cimicidae).

Transtadial persistence and stercorarial shedding of hepatitis B virus (HBV) in common bed bugs, Cimex lectularius L., was studied by using experimental infectious blood feedings, infectious intrathoracic inoculations, and virus detection by polymerase chain reaction and Southern hybridization. Results showed that HBV persisted after an infectious blood meal in bed bug bodies for up to 35 d after the infectious blood meal. It was passed transtadially through one molt regardless of instar, was shed in fecal droplets for up to 35 d after the infectious blood meal, but was not passed transovarially. In bugs inoculated intrathoracically, HBV was detected for 21 d postinoculation. Previous studies detected the hepatitis B surface antigen found on both infectious and noninfectious particles in bed bugs. In this study, the presence of nucleic acids amplified from a conserved core region of the viral genome in bodies and feces of C. lectularius suggests that the HBV virus may be mechanically transmitted in feces or when bugs are crushed, during feeding.

Assessment of hepatitis B virus DNA and hepatitis C virus RNA in the common bedbug (Cimex lectularius L.) and kissing bug (Rodnius prolixus).

OBJECTIVE: Historical clinical studies suggest the potential for insect-borne transmission of human hepatitis viruses. Studies of hepatitis B virus (HBV) persistence in insects were performed before the advent of molecular techniques, and studies to assess possible insect-borne transmission of hepatitis viruses have not yet been performed. The aim of this study was to determine, using molecular techniques, whether HBV and hepatitis C virus (HCV) persist in and are excreted in the feces of the bedbug Cimex lectularius L. and kissing bug Rodnius prolixus after an infectious meal. METHODS: Blood-feeding insects from the insect order Hemiptera (Cimex lectularius L. and Rhodnius prolixus) were fed on blood from infected patients with high titers of HBV, HCV, and control uninfected patients. Insects and insect excrement were collected at weekly intervals and tested for HBV DNA and HCV RNA using the polymerase chain reaction. RESULTS: HBV DNA was detected in bedbugs and excrement up to 6 wk after feeding on an infectious meal. HBV DNA was also detected in most kissing bugs and excrement up to 2 wk after feeding. HCV RNA was not detected in bedbugs at any time after feeding. CONCLUSIONS: We did not detect HCV RNA in bedbugs after feeding on an infectious meal. Our data provide molecular evidence to suggest that HBV may persist in Hemiptera. Additional studies are ongoing to determine whether this viral persistence is capable of infection.

Minocycline as a cause of drug-induced autoimmune hepatitis. Report of four cases and comparison with autoimmune hepatitis.

We describe the clinical and liver biopsy morphologic features for 4 patients with minocycline-induced autoimmune hepatitis (group 1). We compared the serum laboratory values and liver biopsy findings from group 1 with those from 10 patients with sporadic autoimmune hepatitis (group 2). All patients in group 1 had positive serum antinuclear antibody titers, but none had positive serum anti-smooth muscle antibody titers. The morphologic findings of group 1 biopsies were those of autoimmune hepatitis in all 4 patients. In addition, 1 of these biopsy specimens also had scattered single eosinophils, unlike autoimmune hepatitis. The mean histologic activity index scores for patients in groups 1 and 2, respectively, were 6.7 and 5.4. No patients in group 1 had marked bridging fibrosis or cirrhosis, compared with 4 of 10 patients in group 2. Minocycline-induced autoimmune hepatitis is usually identical to sporadic autoimmune hepatitis. The absence of eosinophils does not exclude the possibility of a minocycline cause. In the absence of clinical or morphologic differences, a recent ingestion of minocycline should be excluded before the diagnosis of sporadic autoimmune hepatitis is established. Whether the drug is unmasking latent autoimmune hepatitis is unclear.

The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis C.

We sought to determine whether pretreatment serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis C virus (HCV) correlate with demographic features and other disease characteristics and whether these values influence response to therapy. A total of 1,744 patients with HCV received either interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT determinations at entry visit of 1.3 x ULN cohort. Baseline ALT was not related to gender, race, baseline viral level, or HCV genotype. Using logistic regression analysis, the only demographic feature associated with ALT 1.3 x ULN, in all treatment groups (26 of 105, 24.8% for ALT 1.3 x ULN). We conclude that HCV patients with minimally raised ALT values (

Tattoo application is not associated with an increased risk for chronic viral hepatitis.

OBJECTIVE: Many reports cite tattoo application as an independent risk factor for viral hepatitis. The purpose of this study was to determine whether patients with tattoos are at increased risk for chronic viral hepatitis. METHODS: A total of 212 patients, aged 18-55 yr, who presented to the emergency center and outpatient clinic at a suburban tertiary care hospital participated in the study. Of these, 106 had tattoos and 106 did not. No patient had known liver disease or viral hepatitis. Hepatitis B DNA, hepatitis C RNA, and hepatitis G RNA were measured in the serum using the polymerase chain reaction on stored serum samples. Each participant completed an anonymous questionnaire concerning risk factors for viral hepatitis. RESULTS: Patients with tattoos did not have a higher rate of chronic hepatitis B, C, or G than did a gender-matched group without tattoos. One (0.9%), seven (6.6%), and three patients (2.8%) in the tattoo group were positive for hepatitis B DNA, hepatitis C RNA, and hepatitis G RNA, respectively. Among controls, no patients (0%), three (2.8%), and six (5.6%) patients were positive for hepatitis B DNA, hepatitis C RNA and hepatitis G RNA, respectively (p = 0.815). All infected patients except one in each group reported a risk factor for viral hepatitis. Individuals with tattoos were more likely to have body piercing (p = 0.049; CI = 1.000-1.995), and more than five sexual partners (p = 0.013; CI = 1.073-1.846) than the control group. CONCLUSION: We find no evidence to support the observation that tattoos serve as a risk factor for chronic viral hepatitis.

Immunological responses in patients who have spontaneously eradicated hepatitis C virus infection.

We examined the proliferative responses of peripheral blood mononuclear cells obtained from 60 untreated patients who were seropositive by enzyme immunoassay, but negative for hepatitis C virus (HCV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). We used second- and third-generation recombinant immunoblot assay (RIBA) for further serological characterization. In vitro HCV-specific proliferative responses of mononuclear cells were compared to those of both untreated chronic HCV patients and patients who showed sustained virological response to interferon-alpha monotherapy, in order to assess the relative contribution of the immune response to the eradication of HCV. We found that frequency of responses to nonstructural proteins showed statistically significant differences, which were attributable to vigorous, polyspecific responses by cells from the RIBA-positive patients. In this group, core-specific proliferation was significantly associated with intravenous drug use as route of acquisition. Both other patient groups and the RIBA-indeterminate patients showed indistinguishable frequencies of proliferative responses. No association was detected between residual humoral responses, as determined from the RIBA results, and elapsed time since infection. The frequency of antibodies to NS5 differs between spontaneous cure and chronically infected patients. Cell-mediated and humoral immunity appear to be maintained in this population of patients.

Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.

Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear. We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores. Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes. These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C.

OBJECTIVE: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population. METHODS: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse. RESULTS: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (p < 0.001). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (p < 0.001). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (p < 0.002; relative risk, 3.262; confidence interval [C.I.], 1.912-5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%. CONCLUSION: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.

Sequential serum hepatitis C viral RNA levels longitudinally assessed by branched DNA signal amplification.

The aim of this study was to determine the stability of viral load over an extended period in patients with chronic hepatitis C virus (HCV). Sequential serum specimens collected from fourteen non-alcoholic adult patients with chronic HCV between 1990 and 1997 were tested retrospectively for HCV RNA levels by branched DNA assay (Quantiplex HCV RNA 2.0 [Chiron Diagnostics, Emeryville, CA]). A minimum of three serum samples was obtained at various intervals from each patient. None of the patients received antiviral therapy. Liver biopsies, available for 10 of 14 patients, showed mild or moderate hepatitis in seven and cirrhosis in three (one developed cirrhosis during follow-up). RIBA strip immunoassay showed that 7, 3, and 4 patients had viral genotypes 1, 2, and 3, respectively. The follow-up time averaged 5.3 years (range, 3.7 to 6.6 years). Eight patients (57.2%) showed increased viral levels from baseline to follow-up, the remaining six patients (42.8%) showed decreased viral levels. The three cirrhotic patients had the highest viral levels over time. The mean change was a 0.29-fold decrease (median, +1.14 [corrected]; range, -17.49 to +7.32). A less than twofold change in either direction was demonstrated for six patients (42.8%), and a less than threefold change was demonstrated for 10 patients (71.4%). Variation from baseline to last follow-up as calculated by log determination showed that the viremic load varied less than one log10 in all but one individual. These results show that viral load remains relatively stable over prolonged periods in most untreated patients with chronic hepatitis C.

Clinical outcome of hepatitis C as a function of mode of transmission.

Several reports suggest that posttransfusion hepatitis C causes more aggressive histological activity than disease that is acquired via other routes. We sought to determine whether mode of transmission affects disease outcome. We studied the demographics, presenting laboratory data, and clinical course of 627 consecutively evaluated nonalcoholic patients with chronic hepatitis C. Two hundred eighty-two patients (45%) were transfusion recipients, 262 (42%) acquired the disease via other routes of percutaneous exposure, and 83 (13%) were without risks. Liver histology was available in 463 patients (215 transfusion recipients, 195 non-transfusion recipients, and 53 who were were without risks) and showed noncirrhosis in 274 (59%), cirrhosis in 173 (37%), and hepatocellular carcinoma in 16 patients (4%) who also had underlying cirrhosis. Duration of follow-up was 1 to 25 years (mean, 48 months; median, 21 years). One hundred eighteen of 173 (68%) cirrhotic patients were transfusion recipients; 40 of 173 (23%) cirrhotic patients acquired infection via other percutaneous exposure, and the remainder were without known risk factors (P < .001). Among the 215 patients with blood transfusions for whom histology was available, 118 of 215 (55%) had cirrhosis and 89 of 215 (41%) were noncirrhotic (P < .001); 8 transfused patients (4%) had hepatocellular carcinoma. In the percutaneous group, 40 of 195 (21%) of the patients were cirrhotic versus 153 of 195 (78%) who were noncirrhotic (P < .001); 2 patients (1%) had hepatocellular carcinoma. During the follow-up period, 59 of 189 (31%) of the cirrhotic patients (including those 16 individuals with hepatocellular carcinoma) developed hepatic decompensation. By univariate analysis, the risk of liver failure was related to age at viral acquisition, but by logistic regression analysis, only mode of transmission, and not age or estimated disease duration, predicted risk of liver failure. Patients with posttransfusion hepatitis C were more likely to develop decompensation than individuals who were not transfusion recipients (relative risk, 3.921; CI = 2.205 to 7.015). Serum albumin, prothrombin time, and platelet count at presentation were independent laboratory predictors of subsequent hepatic decompensation. The rate of hepatocellular carcinoma development among all cirrhotic patients during the follow-up period was 1.2% per year. Patients with posttransfusion hepatitis C are at greater risk of cirrhotic decompensation than those individuals with non-transfusion-acquired disease. The risk of liver failure is more closely related to the mode of transmission than to age at viral acquisition or to the duration of infection.

Alfa interferon treatment of hepatitis C virus RNA-positive patients with normal or near-normal alanine aminotransferase levels.

OBJECTIVES: Alfa interferon therapy is conventionally offered only to chronic hepatitis C patients with abnormal serum alanine aminotransferase (ALT) values. Therapeutic response is traditionally gauged by normalization of liver enzymes. Treatment of patients with persistently normal serum aminotransferases is not routinely done. The purpose of this study was to determine whether standard therapy with alfa interferon can eradicate hepatitis C virus in viremic patients with persistently normal or near-normal serum aminotransferases. METHODS: Between 1990 and 1996 we evaluated 565 patients with chronic hepatitis C. Of these, 49 patients (8.7%) (15 men, 34 women) had normal or near-normal ALT levels (less than 1.5 times upper limit of normal) for at least 3 consecutive months. Of these, 15 patients were studied. Treatment consisted of interferon alfa-2b 3 million units thrice weekly for 6 months. RESULTS: Normal or near normal ALT levels are more common in women than men. All patients completed 6 months of therapy, and 12 patients completed 6 months of posttreatment follow-up. Only one patient lost hepatitis C virus RNA during treatment and viremia reappeared in this patient immediately after cessation of therapy. CONCLUSIONS: Standard antiviral therapy of patients with normal or near-normal ALT levels does not result in sustained viral eradication in most patients.

Experimental evidence against replication or dissemination of hepatitis C virus in mosquitoes (Diptera:Culicidae) using detection by reverse transcriptase polymerase chain reaction.

In 3 laboratory experiments, mosquitoes were fed hepatitis C virus (HCV)-RNA positive blood by using membrane feeders, separated into head, thorax, and abdomen, and tested by a reverse transcriptase polymerase chain reaction for HCV-RNA. HCV did not replicate or disseminate in mosquitoes that had ingested blood from patients that were HCV-viremic positive. When yellow fever mosquitoes, Aedes aegypti (L.), were held for 1, 3, 7, 14, and 21 d after feeding, HCV-RNA was detected in the abdomens of 5/5 mosquitoes at 1 d after feeding; remaining tissues were negative with the exception of a single positive head at 7 d. In agreement, HCV-RNA was detected in Asian tiger mosquito, Aedes albopictus Skuse, and Anopheles stephensi Liston abdomens at 1 d, but not 3 d after feeding no HCV-RNA was detected in heads or thoraces. In addition, HCV-RNA was detected in heads of Ae. aegypti at 10 and 20 min, but not at 30 min, after feeding. The latter results raise the possibility of HCV contamination of mouthparts and, theoretically, mechanical transmission of this virus.

Decreased levels of 13-hydroxyoctadecadienoic acid (13-HODE) dehydrogenase in neoplastic tissue of human colon biopsies.

Recent studies have identified a role for the oxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (13-HODE) in cell proliferation. The enzyme 13-HODE dehydrogenase catalyzes the conversion of 13-HODE to 13-oxooctadecadienoic acid. This enzyme has been shown to correlate with the degree of differentiation of intestinal cells in both in vitro and in vivo models. Higher enzyme levels are found in more differentiated cell types. The present study was done to determine if enzyme levels of 13-HODE dehydrogenase are predictive of the differentiation status of biopsies from human colonic mucosa. Twenty-eight patients who underwent diagnostic colonoscopy (10 patients with adenocarcinoma and 18 with adenomatous polyps) had biopsies taken from both normal rectal mucosa and neoplastic mucosa. The determination of 13-HODE dehydrogenase activity was conducted by high-performance liquid chromatography analysis of all biopsy samples. Sixteen of the 18 patients with polyps had lower 13-HODE dehydrogenase activity in the adenoma than in the uninvolved rectal mucosa (P = 0.001). The colon adenocarcinomas also had less 13-HODE dehydrogenase activity in the cancer biopsy tissue than in uninvolved rectal mucosa (P = 0.041) These data are consistent with a role for 13-HODE dehydrogenase in intestinal cell differentiation. Understanding the precise role of this enzymatic reaction could be important potentially in the therapy and biology of colon cancer. In addition, measurements of 13-HODE dehydrogenase may be a useful parameter by which to ascertain the differentiation status of intestinal cells in vitro.

Antibodies to carbonic anhydrase in patients with immune cholangiopathies.

BACKGROUND/AIMS: Bile duct epithelia contain an abundance of carbonic anhydrase. Antibodies to this enzyme have been described in autoimmune disorders. Serum from patients with immune-mediated liver diseases was studied to determine whether antibodies to carbonic anhydrase II and/or pyruvate dehydrogenase could distinguish autoimmune cholangitis as immunologically distinct from primary biliary cirrhosis. METHODS: Antibody assays to carbonic anhydrase II (Western blot) and pyruvate dehydrogenase (flow cytometry) were performed on the sera of patients with autoimmune cholangitis (6), primary biliary cirrhosis (12), primary sclerosing cholangitis (12), autoimmune hepatitis (12), and control (Gilbert syndrome; 8). RESULTS: Reactivity to carbonic anhydrase II was detected in 5 of 6 patients with autoimmune cholangitis, 1 of 12 patients with primary biliary cirrhosis, 1 of 12 patients with autoimmune hepatitis, and no other patients. Individuals with autoimmune cholangitis were more likely than the other patients to be reactive to carbonic anhydrase II (P < 0.001). Patients with primary biliary cirrhosis were more reactive to pyruvate dehydrogenase compared with all other groups (P < 0.001). CONCLUSIONS: An antibody to human carbonic anhydrase II is frequently detected in the sera of patients with autoimmune cholangitis and is uncommon or not present in other cholangiopathies. These data provide evidence that autoimmune cholangitis and primary biliary cirrhosis represent distinct entities with unique patterns of immunoreactivity.

Cryptogenic liver disease in the United States: further evidence for non-A, non-B, and non-C hepatitis.

UNLABELLED: Since the advent of anti-hepatitis C virus (HCV)-testing, the current worldwide prevalence of cryptogenic cirrhosis is essentially unknown. OBJECTIVES: 1) determine if serum HCV RNA testing by the polymerase chain reaction (PCR) enhances the diagnostic yield for HCV in patients with anti-HCV-negative cryptogenic liver disease and 2) further define the epidemiology of patients with indeterminate causes of chronic hepatitis and cirrhosis. METHODS: We reviewed the records of 567 patients with chronic liver disease who were evaluated over a 3-yr period. A definite etiology for liver disease was established in all but 28 patients (4.9%). Histology was available in 20 patients. RESULTS: Twenty-one of the 28 patients were female (mean age, 52 yr). Thirteen patients (46%) had a history of previous blood transfusion, and one patient was a health care worker. Histology revealed CAH/cirrhosis in 17 patients, CPH in one patient, and no diagnosis in two patients. Five additional patients had clinically advanced cirrhosis. None of the 28 patients with cryptogenic chronic liver disease was HCV RNA positive by PCR. CONCLUSIONS: 1) Approximately 5% of patients with chronic hepatitis/cirrhosis remain cryptogenic despite the addition of HCV RNA testing. 2) PCR does not improve the diagnostic yield in this population. 3) Nearly half of the patients with presumed cryptogenic cirrhosis have been transfused, supporting the hypothesis of a non-A, non-B, and non-C hepatitis virus. 4) Screening donor blood for serum ALT may still be necessary to further reduce posttransfusion hepatitis.

Levels of hepatitis C virus RNA and liver histology in chronic type C hepatitis.

BACKGROUND: The clinical and pathologic significance of quantitative serum hepatitis C virus (HCV) RNA levels in patients with chronic type C hepatitis is unknown. The aim of this study was to determine whether serum levels of HCV RNA were associated with mode of viral transmission or with histological severity of liver disease. METHODS: A branched DNA signal amplification assay for HCV RNA was done on the sera of 127 patients with well-defined risk factors for viral hepatitis. Seventy persons acquired HCV infection by blood transfusion and 57 via tattoo application or former intravenous drug use. Group I included 42 patients with chronic persistent hepatitis, group II consisted of 39 patients with chronic active hepatitis, and group III included 40 individuals whose liver biopsies showed both chronic active hepatitis and cirrhosis, as well as six patients with clinically decompensated cirrhosis. RESULTS: The median HCV RNA level [equivalents/ml (eq/ml) x 10(5)] for patients who acquired infection from transfusion [73.5 x 10(5) (eq/ml)] was not significantly different from that of patients who reported prior intravenous drug use [50 x 10(5) eq/ml] (p = 0.283). The median HCV RNA level for groups I, II, and III was 29.5, 76, and 71, respectively. Group I differed significantly from groups II and III combined (median = 73) (p = 0.02). No difference was noted between group II and group III (p = 0.947). Age did not correlate with level of viremia (r2 = 0.01). No relationship was found between serum alanine aminotransferase and the level of viremia (p = 0.52). Multivariate analysis showed that only the histological severity of the disease proved to be predictive of HCV RNA level (p = 0.04). CONCLUSION: The lowest levels of hepatitis C viremia are, in general, associated with minimal liver disease. Overall, histological severity of chronic hepatitis C infection best predicts HCV RNA levels.

HCV RNA is present in the menstrual blood of women with chronic hepatitis C infection.

OBJECTIVES: To further determine potential routes of sexual transmission of hepatitis C virus (HCV), we examined the menstrual blood of women chronically infected with this virus. METHODS: Ten premenopausal women with documented HCV infection were studied. All patients were anti-HCV positive by ELISA-II and positive for HCV RNA by polymerase chain reaction. Eight patients acquired their infection via intravenous drug abuse, one patient through blood transfusion, and one patient was a health care worker. Liver biopsies showed evidence of chronic hepatitis in all patients. Menstrual blood was collected on the first day of menses utilizing a sterile 15-ml conical centrifuge tube. Total RNA was isolated from serum by the one-step guanidinium method. Reverse transcriptase polymerase chain reaction was performed with "nested" primers from the 5' noncoding region of the HCV genome. All samples were run twice, and negative controls were run with each sample. Three anti-HCV negative volunteers served as controls. RESULTS: HCV RNA was present in the menstrual blood of all chronically infected patients tested. All controls were negative for menstrual blood HCV RNA. CONCLUSIONS: 1) HCV RNA is routinely present in the menstrual blood of women chronically infected with this virus. 2) Knowledge of the presence of HCV RNA in menstrual blood should help facilitate appropriate guidelines for the sexual counseling of patients with chronic HCV infection.

Altered levels of prothymosin immunoreactive peptide, a growth-related gene product, during liver regeneration after chronic ethanol feeding.

Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several proto-oncogenes, including c-myc, which peaks 3-6 hr post-partial hepatectomy. Prothymosin alpha, a gene encoding a ubiquitous nuclear protein, is activated by c-myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin alpha mRNA levels reportedly increase 12-32 hr post-partial hepatectomy, several hours after c-myc induction. We sought to determine if chronic ethanol intake alters the expected induction post-partial hepatectomy of prothymosin alpha steady-state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair-fed controls, we found no significant differences in steady-state levels of prothymosin alpha mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady-state mRNA levels, but may occur post-transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.

Lack of evidence for the heterosexual transmission of hepatitis C.

To determine the potential for sexual transmission of the hepatitis C virus (HCV), we specifically studied a cohort of 42 young adults (median age, 39 yr) with chronic HCV infection and their stable sexual partners. All HCV assays were supplemented with the four-antigen recombinant immunoblot assay, and 39 of 42 partners were tested for HCV RNA by the nested polymerase chain reaction. Ninety percent of the partners reported frequent and unprotected sexual intercourse with the index patients. Two of 42 partners tested positive for the anti-HCV antibody and both were HCV RNA positive; one had independent risk factors for viral hepatitis. Therefore, one of 41 partners, (2.4%; 95% CI, 0.6-12.9%) without independent risk factors for HCV was anti-HCV positive. This woman was one of five partners (20%; 95% CI, 1-66%) who reported frequent razor-sharing with the index patient. The partner frequently sustained skin lacerations, with bleeding, secondary to this shared razor blade. We conclude that heterosexual transmission of hepatitis C is extremely uncommon, despite frequent and unprotected sexual intercourse.