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Objectives: Needle liver biopsy has been shown to have a high rate of sampling error in patients with diffuse parenchymal liver diseases. In these cases, the sample of liver tissue does not reflect the true degree of inflammation, fibrosis, or cirrhosis, despite an adequate sample size. The aim of this study was to determine the rate and extent of sampling error in patients with chronic hepatitis C virus infection, and to assess the intraobserver variation with the commonly used scoring system proposed by Scheuer and modified by Batts and Ludwig., Methods: A total of 124 patients with chronic hepatitis C virus infection underwent simultaneous laparoscopy-guided biopsies of the right and left hepatic lobes. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin and with trichrome. The slides were blindly coded and randomly divided among two hepatopathologists. Inflammation and fibrosis were scored according to the standard grading (inflammation) and staging (fibrosis) method based on the modified Scheuer system. Following the interpretation, the slides were uncoded to compare the results of the right and left lobes. Fifty of the samples were blindly resubmitted to each of the pathologists to determine the intraobserver variation., Results: Thirty of 124 patients (24.2%) had a difference of at least one grade, and 41 of 124 patients (33.1%) had a difference of at least one stage between the right and left lobes. In 18 patients (14.5%), interpretation of cirrhosis was given in one lobe, whereas stage 3 fibrosis was given in the other. A difference of two stages or two grades was found in only three (2.4%) and two (1.6%) patients, respectively. Of the 50 samples that were examined twice, the grading by each pathologist on the second examination differed from the first examination in 0% and 4%, and the staging differed in 6% and 10%, respectively. All observed variations were of one grade or one stage., Conclusions: Liver biopsy samples taken from the right and left hepatic lobes differed in histological grading and staging in a large proportion of chronic hepatitis C virus patients; however, differences of more than one stage or grade were uncommon. A sampling error may have led to underdiagnosis of cirrhosis in 14.5% of the patients. These differences could not be attributed to intraobserver variation, which appeared to be low.

Hepatitis C viral infection is currently the leading cause of chronic hepatitis and cirrhosis. It also is a major predisposing factor for the development of hepatocellular carcinoma. It is estimated that approximately 1-2% of patients with hepatitis C infection have nonhepatic manifestations that are protean in nature. In this report, we describe six unusual cases of nonhepatic manifestations: abdominal vasculitis in two, peripheral neuropathy in two, and one patient each with central nervous system vasculitis and necrotizing cutaneous vasculitis. All patients had cutaneous vasculitis and cryoglobulinemia. None of our patients had cirrhosis, yet three of the six patients died. Because of the severe manifestations, aggressive therapy was instituted with interferon, immunosuppressive medications, i.v. immunoglobulin, and plasmapheresis. Our report underscores the importance of recognizing nonhepatic manifestations in patients with hepatitis C infection that may be associated with high morbidity and mortality.

Unlabelled: Chronic hepatitis develops in at least half of persons acutely infected with hepatitis C virus (HCV). Ten to 25% of these patients will develop cirrhosis. Serum procollagen-III peptide (PIIIP) may be of value in predicting the development of chronic active fibrogenic liver disease. It has been reported that in chronic viral C hepatitis, the levels of hepatitis C virus-RNA (HCV-RNA) correlate directly with the severity of hepatic histology and inversely with response to interferon therapy., Objectives: The aims of this study were to correlate the level of PIIIP with HCV-RNA concentrations, ALT values, and histological severity in patients with chronic viral C hepatitis., Methods: Eighty-six patients with chronic C hepatitis were divided into three groups: group I (n = 34), mild chronic active hepatitis, group II (n = 25), moderate to severe chronic active hepatitis, and group III (n = 27), cirrhosis. HCV-RNA was measured by Quantiplex, and PIIIP was measured by radioimmunoassay-gnostic assay., Results: Mean +/- SD level of ALT in group I was 114 +/- 48 U/L, group II was 169 +/- 115 U/L, and group III was 160 +/- 94 U/L. The mean +/- SD level of HCV-RNA in group I was 110 +/- 130 x 10(5) Eq/ml, in group II was 140 +/- 140 x 10(5) Eq/ml, and in group III was 70 +/- 80 x 105 Eq/ml. The mean +/- SD level of PIIIP in group I was 0.6 +/- 0.2 U/ml, in group II was 0.9 +/- 0.4 U/ml, and in group III was 1.2 +/- 0.6. There was a significant difference in the levels of PIIIP among the three groups (p = 0.0001). There was no correlation among ALT, HCV-RNA, and PIIIP in any of the three groups., Conclusions: PIIIP peptide determinations in patients with chronic viral C hepatitis are reflective of histological severity and may provide relatively noninvasive means of following disease progression.

Diagnostic laparoscopy continues to have a role in the evaluation and diagnosis of acute and chronic liver diseases, primary and metastatic liver tumors, and peritoneal diseases. We retrospectively reviewed the records of 1794 diagnostic laparoscopies performed at our institution from 1987 to 1992 to identify the indications, results, and safety of this procedure in our training program. A definitive diagnosis was made in 91% of cases with biopsy performed in 93%. Chronic liver disease was evaluated in 890 patients, and a diagnosis was made in 98%. Four hundred thirty-seven patients were evaluated for suspected primary or metastatic carcinoma, and a diagnosis was made in 85%. Ascites was evaluated in 73 patients, and a diagnosis was made in 82%. One-hundred sixty-four patients were evaluated for abnormal liver function tests, and a diagnosis was made in 91%. HIV-related liver function test abnormalities were evaluated in 67 patients, and a diagnosis was made in 81%. One hundred sixty-three patients underwent diagnostic laparoscopy for the evaluation of hepatomegaly, splenomegaly, unexplained portal hypertension, fever of unknown origin, and cholestasis, and a diagnosis was made in 74% of cases. Eight major complications (including abdominal viscus perforation, hemobilia, splenic laceration, bleeding) and thirty-one minor complications were seen. Our findings confirm that diagnostic laparoscopy is a safe and valuable procedure in the evaluation of chronic liver disease.

In this study we have attempted to classify a group of North American patients with autoimmune chronic hepatitis into types I, II, and III according to the class of autoantibody present in serum, and determine the prevalence and significance of antibody to hepatitis C virus (anti-HCV). A total of 62 patients (type I, 51; type II, 3; type III, 8) were tested with first-generation enzyme-linked immunosorbent assay (ELISA)-1. Seropositive patients were assessed by second-generation recombinant immunoblot assay (RIBA)-2 and polymerase chain reaction (PCR). Our results demonstrate that 12 (19%) of the 62 patients with autoimmune hepatitis were anti-HCV ELISA-1 positive (type I, 9; type II, 1; type III, 2). Only one patient with type II autoimmune hepatitis was reactive by RIBA-2 and PCR. Eight of the 12 seropositive patients entered remission after corticosteroid therapy and seven of them became seronegative by ELISA-1. The RIBA-2 and PCR reactive patient did not respond to immunosuppressive therapy and remained seropositive. We conclude that there is a low prevalence of anti-HCV antibody in autoimmune hepatitis. Results based only on ELISA-1 anti-HCV testing can be misleading, and second-generation testing is necessary to recognize the presence of HCV infection. The fact that the only RIBA-2 reactive patient had type II autoimmune hepatitis may suggest a role for HCV infection in the pathogenesis of this condition. Nevertheless, corticosteroid therapy remains effective in those patients who are ELISA-1 seropositive, but RIBA-2 and PCR nonreactive.

Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity.

Fulminant hepatic failure (FHF) due to acute hepatitis B and delta co-infection occurred in a 74-yr-old female, who eventually died. There was no clear-cut epidemiology other than probable bloodborne transmission from a contaminated spring-loaded fingerstick device used for glucose determination, in an outpatient facility. This unusual mode of transmission reiterates the importance of using sterile cleansing and disposal procedures anytime there is a possibility of contamination with blood.

A 37-yr-old man with portal hypertension due to portal vein thrombosis was referred because of recurrent episodes of variceal hemorrhage. He had previously undergone two portal-systemic shunt procedures. Both of the shunts, as well as the superior mesenteric vein, ultimately thrombosed. Endoscopic variceal sclerotherapy was able to control the bleeding from his esophageal varices, but he repeatedly bled from large gastric varices. The patient underwent a total gastrectomy and has had no further gastrointestinal hemorrhage during a follow-up of 36 months.

Acute fatty liver of pregnancy, a disease of the 3rd trimester of pregnancy, may have varied presentations. An unusual initial presentation of acute fatty liver of pregnancy mimicking an acute viral hepatitis is reported herein. Osmium tetroxide preparation of pathological specimen for the diagnosis of acute fatty liver of pregnancy is also discussed.

A 44-yr-old homosexual male with symptomatic human immune deficiency virus (HIV) infection presented with abdominal pain, hepatosplenomegaly, and rising serum alkaline phosphatase. Laparoscopy revealed multiple purplish nodules on the surface of the liver. Histopathology of the lesions was consistent with Kaposi's sarcoma. Six weeks later, cutaneous Kaposi's sarcoma became apparent on the head and neck. This case is unusual because, in all previously published cases, with the exception of one, intrahepatic Kaposi's sarcoma was found on autopsy. Moreover, all patients had evidence of extrahepatic Kaposi's sarcoma prior to the documentation of liver involvement.

Echinococcosis is a disease which is commonly seen in certain parts of the world and uncommonly seen in the United States. Recognition of this disease is important for appropriate surgical management with the least amount of morbidity and mortality. Proper history taking and awareness of this disease will decrease the chance of misdiagnosis. Two cases are presented here, and the salient features of this disease are reviewed, in order to reacquaint the physician.

A 39-yr-old female on high-dose Danazol presented with jaundice and pruritus. Danazol-induced cholestasis was suspected, and the drug was discontinued. A liver biopsy revealed panlobular cholestasis with portal and periportal inflammation. The cholestasis resolved completely in 8 wk. This is a rare case of Danazol-induced cholestasis and should be considered in the differential diagnosis of drug-induced liver injury.

Acetaminophen, a commonly used medication, is present in many over-the-counter remedies. In recent years, its potential to cause severe liver injury has been increasingly appreciated. Chronic abusers of alcohol may be particularly susceptible to hepatotoxicity from acetaminophen. We report two cases of unintentional liver injury associated with ingestion of Nyquil, a liquid cold remedy containing acetaminophen and 25% alcohol.

Salmonella represents an infrequent cause of spontaneous bacterial peritonitis in cirrhotic ascites. A cirrhotic patient, an alcoholic and former intravenous drug abuser, developed spontaneous group B Salmonella enteritidis (undetermined serotype) bacterial peritonitis. The isolation of this pathogen, a common cause of bacteremia in acquired immune deficiency syndrome, led to the serological determination of infection with human immune deficiency virus (HIV).