Clindamycin-induced acute cholestatic hepatitis

We report a case of acute hepatotoxicity in a 42-yearold woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase （ALT）, 1795 IU/L （normal range 0-40）; aspartate aminotransferase （AST）, 1337 IU/L （normal range 5-34）; alkaline phosphatase （ALP）, 339 IU/L （normal range 40-150）; 7-glutamyl transpeptidase （GGT）, 148 IU/L （normal range 9-64 IU/L）; total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time （PT）, 13.5 s, with international normalized ratio （INR）, 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type （both hepatocellular and cholestatic） hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixedtype liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.     

Epstein–Barr Virus (EBV) Related Acute Liver Failure: A Case Series from the US Acute Liver Failure Study Group

Purpose

Acute liver failure (ALF) is a rare clinical syndrome associated with a high case fatality rate. Asymptomatic primary infection with Epstein–Barr virus (EBV) is common in the general population while acute hepatitis and jaundice are much less common and ALF has been rarely reported. We reviewed the presenting features as well as clinical outcomes amongst consecutive adults with EBV-related ALF.

Methods

Amongst the 1,887 adult ALF patients enrolled into the US ALF Study Group from January 1998 to February 2012, there were four patients (0.21 %) with EBV-related ALF. Diagnostic criteria for acute EBV infection included compatible serologies and/or the detection of EBV-encoded RNA (EBER) in liver tissue.

Results

Median patient age was 30 years (range 18–44); 75 % were male, and only 25 % were immunosuppressed. The median presenting ALT was 504 IU/mL (range 156–4,920), median Alk P was 431 (range 136–1,009), and median bilirubin was 17 mg/dL (range 13–22.1). Liver biopsy findings ranged from cholestasis to submassive necrosis with EBER + staining in two of the three samples tested. Although all of the patients were treated with an antiviral agent, two died of ALF, one underwent liver transplantation (LT) and one survived with supportive care and is well at 5 years. A review of the literature identified four additional LT recipients with favorable long-term outcomes.

Conclusion

Primary EBV infection accounts for <1 % of consecutive adult ALF cases but is associated with a high case fatality rate. LT is associated with favorable short- and long-term outcomes.     

Clinical significance of elevated alpha-fetoprotein (AFP) in chronic hepatitis C without hepatocellular carcinoma

BACKGROUND/AIMS: Alpha-fetoprotein is often measured in subjects with chronic hepatitis C for diagnosing hepatocellular carcinoma. However, its prevalence and clinical significance remain inconclusive in subjects without hepatocellular carcinoma. The study was to assess the clinical, virologic, and histopathological significance of elevated AFP in chronic hepatitis C without the presence of hepatocellular carcinoma. METHODOLOGY: The retrospective study enrolled 102 consecutive subjects with a histological diagnosis of chronic hepatitis C. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 6 months' follow-up. The correlation between serum alpha-fetoprotein level and clinical, virologic, or histopathological records was reviewed. RESULTS: The prevalence of elevated serum alpha-fetoprotein (> or = 13.6 ug/L) was 28.4% (29/102) in this study. Hepatic steatosis (> or = 5% hepatocytes), hepatic fibrosis (> or = stage II), uric acid > or = 6.3 mg/dL, asparate aminotransferase > or = 40 IU/L, albumin < 3.5 g/dL, and fasting plasma glucose < 126 mg/dL were significantly associated with elevated AFP in multivariate analysis. However, neither hepatitis C virus genotype Ib infection nor viral load > or = 1x10(6) copies/ml was related to elevated AFP. A serum alpha-fetoprotein level of 15.6 ug/L was 34.3% sensitive and 83.6% specific for hepatic steatosis, was 28.2% sensitive and 95.8% specific for > or = stage II hepatic fibrosis in Chronic hepatitis C. CONCLUSIONS: Elevated alpha-fetoprotein is independently associated with hepatic steatosis (> or = 5% hepatocytes), > or = stage II hepatic fibrosis, increased level of uric acid (> or = 6.3 mg/dL) or asparate aminotransferase (> or = 40 IU/L), and decreased level of albumin (< 3.5 g/dL) or fasting plasma glucose (< 126 mg/ dL). Viral factors, including hepatitis C virus genotype 1b infection and viral load, are not related to elevated alpha-fetoprotein in hepatitis C virus-infected subjects.     

HTLV-1 associated acute adult T-cell lymphoma/leukemia presenting as acute liver failure in Micronesian: A case report

Rationale:Malignant infiltration accounts for 0.5% of acute liver failure cases, with non-Hodgkin''s lymphoma the predominant cause. Adult T-cell lymphoma/leukemia (ATLL) is a rarer source of acute hepatitis, with only 3 cases reported and all resulting in immediate deterioration with death. ATLL rises from human T-lymphocytic virus-1 (HTLV-1), commonly found in Japan (southern and northern islands), the Caribbean, Central and South America, intertropical Africa, Romania, and northern Iran. In Micronesia, HTLV-1 infection amongst native-born is absent or exceedingly rare.Patient Concerns:A 77-year-old Marshallese man presented to the emergency department with a 1-week history of generalized weakness, fatigue, and nausea. The physical exam revealed a cervical papulonodular exanthem and scleral icterus.Diagnosis:Laboratory studies were remarkable for aspartate-aminotransferase of 230 IU/L (reference range [RR]: 0–40), alanine-aminotransferase of 227 IU/L (RR: 0–41), alkaline phosphatase of 133 IU/L (RR: 35–129), and total bilirubin of 4.7 mg/dL (RR: 0–1.2), supporting acute liver injury. Platelet count was 11.6x10⁴/μL (RR: 15.1–42.4 × 10⁴), hemoglobin was 13.8 g/dL (RR: 13.7–17.5), and white blood cell count was 7570/μL (RR: 3800–10,800) with 81.8% neutrophils (RR: 34.0–72.0) and 10.4% lymphocytes (RR: 12.0–44.0). The peripheral blood smear demonstrated abnormal lymphocytes with occasional flower cell morphology. HTLV-1/2 antibody tested positive. The skin and liver biopsies confirmed atypical T-cell infiltrate. The diagnosis of ATLL was established.Interventions:The patient elected for palliative chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). He began antiviral treatment with zidovudine 250 mg bis in die (BID) indefinitely. Ursodiol and cholestyramine were added for his hyperbilirubinemia.Outcomes:Four weeks from admission, the patient returned to near baseline functional status and was discharged home.Lessons:This case highlights that ATLL can initially present as isolated acute hepatitis, and how careful examination of peripheral blood-smear may elucidate hepatitis etiology. We also present support for utilizing ursodiol with cholestyramine for treating a hyperbilirubinemia. Moreover, unlike prior reports of ATLL presenting as liver dysfunction, combined antiviral and CVP chemotherapy was effective in this case. Lastly, there are seldom demographic reports of HTLV-1 infection from the Micronesian area, and our case represents the first indexed case of HTLV-1-associated-ATLL presenting as acute liver failure in a Marshallese patient.     

Expression and clinical significance of antinuclear antibody in hepatitis C virus infection

BACKGROUND: The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY: Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS: Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS: Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.     

Prolonged acute hepatitis A mimicking autoimmune hepatitis

AIM: We report a case with a prolonged course of hepatitis A, with alanine aminotransferase (ALT) higher than 500 IU/L for more than 2 mo. METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive anti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out. RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCA proved to be effective.     

Autoimmune hepatitis triggered by acute hepatitis A

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (x320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.     

Obesity and diabetic hyperglycemia were associated with serum alanine aminotransferase activity in patients with hepatitis B infection

Several studies have reported that obesity and diabetes are important risk factors for elevated blood aminotransferase activity in individuals with no underlying causes of liver disease. The aim of this study was to determine whether obesity and fasting glucose level were associated with hepatic dysfunction in patients with hepatitis B infection. A total of 934 patients with hepatitis B infection were enrolled, among whom increased alanine aminotransferase (ALT) activity (≥40 IU/L) was observed in 25.1%. By univariate analysis, factors associated with increased ALT activity among patients with hepatitis B infection included body mass index (BMI), fasting blood glucose level, and blood triglyceride and high-density cholesterol levels. By multivariate logistic regression analysis, BMI and fasting blood glucose level were independent predictors of elevated ALT activity, with odds ratios of 1.73 (95% confidence interval, 1.17-2.56) for subjects with a BMI greater than or equal to 25 kg/m² and 1.88 (95% confidence interval, 1.06-3.33) for subjects with a fasting blood glucose greater than or equal to 126 mg/dL. Even in subjects with ALT activity within the reference range, ALT activity was found to be associated with BMI. In conclusion, a BMI greater than or equal to 25 kg/m² and a fasting blood glucose level greater than or equal to 126 mg/dL were risk factors for increased ALT activity in subjects with hepatitis B infection, suggesting that obesity and diabetic fasting hyperglycemia may aggravate liver injury in this population.     

Role of needle knife assisted ampullary biopsy in the diagnosis of periampullary carcinoma

AIM:To study the role of needle knife assisted ampullary biopsy in the diagnosis of periampullary carcinoma.METHODS:In this study the authors retrospectively analyzed clinical records of patients with periampullary tumors diagnosed by ampullary biopsy taken after needle knife papillotomy in whom surface ampullary biopsies were non contributory.RESULTS:Between January 2008 and December 2010,38 patients with periampullary tumors were seen by us and initial side viewing endoscopy with surface biopsy from the papilla was positive for malignancy in 25 patients.Thirteen patients with a negative surface biopsy for malignancy underwent a repeat ampullary biopsy following needle knife papillotomy.There were 8(61.5%)males and 5(38.5%)females.The most common presenting symptom was jaundice(100%),followed by fever(46.2%),melena(38.5%),abdominal pain(30.8%)and weight loss(30.8%).All the patients had hyperbilirubinemia with a mean ± SD serum bilirubin of(11.2 ± 1.9)mg/dL(normal value <1 mg%)and the mean ± SD serum alkaline phosphatase was(288.0 ± 94.3)IU/L(normal value < 129 IU/L).Serum CA 19.9 level estimation was done in 11 patients;it was elevated(cut off value > 70.5 IU/L)in all of them with a median of 1200 IU/L(inter quartile range 274-3500).Side viewing endoscopy showed a bulky papilla in all of them.Adequate tissue was obtained in all of the 13 patients for histological evaluation;12 of the 13 patients were reported to have adenocarcinoma while one patient had adenoma.There were no complications from the needle knife papillotomy in any of the patients.CONCLUSION:Needle knife assisted ampullary biopsy appears to be a safe and effective diagnostic modality for periampullary carcinoma.     

Temporal profile of HEV RNA concentration in blood and stool from patients with acute uncomplicated hepatitis E in a region with genotype 1 predominance

Acute hepatitis E virus (HEV) is associated with viremia and faecal excretion of the virus. The information on duration and temporal pattern of viremia and faecal shedding in HEV infection is important, but is not available. Serial serum and stool specimens were collected from patients with acute hepatitis E (typical clinical picture, serum alanine aminotransferase levels > 5‐folds the upper limit of normal and presence of IgM anti‐HEV), beginning from within 7 days of the onset of symptoms. HEV RNA concentrations were measured in sera and 10% stool suspensions, using a real‐time Taqman‐based nucleic acid amplification assay. Seventeen patients (median age 25 [range 19‐61] years; all men) were enrolled within a median of 5 (range 3‐8) days of the onset of the first symptom and provided 113 serum specimens and 71 stool specimens. The median (range) highest levels of serum bilirubin, alanine aminotransferase and aspartate aminotransferase in the patients were 10.3 (5.9‐43.4) mg/dL, 1817 (442‐4642) IU/L and 1016 (88‐4561) IU/L, respectively. All the 17 patients had demonstrable viremia, and 12 of the 13 patients who were tested had faecal excretion at one or more time points. The HEV RNA titres were the highest in the early phase of disease and declined rapidly with time, becoming nondetectable in the serum by day 20 and in the stool by day 21. In most of the patients with acute uncomplicated acute hepatitis E, the degree of viremia and faecal shedding decline quickly after the onset of clinical illness and rapidly disappear in parallel with each other.     

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.     

Case of idiopathic portal hypertension complicated with autoimmune hepatitis

We report a case of idiopathic portal hypertension (IPH) complicated with autoimmune hepatitis. A 60‐year‐old woman was admitted to our hospital with esophageal and gastric varices in February 2010. Abdominal ultrasonography and computed tomography showed splenomegaly and collateral veins without evidence of liver cirrhosis. Laboratory examinations and liver biopsy indicated that the esophageal and gastric varices were caused by IPH. She underwent endoscopic injection sclerotherapy and partial splenic embolization. Two years after these therapies, laboratory examinations showed liver dysfunction with elevated levels of aspartate aminotransferase (180 IU/L), alanine aminotransferase (190 IU/L), γ‐glutamyl transpeptidase (159 IU/L) and immunoglobulin G (2609 mg/dL). The titer of antinuclear antibodies was 1:320 and its pattern was homogeneous and speckled. Histological examination revealed plasma cell/lymphocyte infiltration and interface hepatitis in the portal tract. Based on these findings, a diagnosis of autoimmune hepatitis accompanied by IPH was made. After treatment with prednisolone (20 mg/day), liver functions were normalized immediately. Overlapping of IPH and AIH is extremely rare, but the present case is interesting considering the etiology of IPH because an autoimmune mechanism is thought to be involved in the pathogenesis of IPH.     

Primary Epstein-Barr virus infection with neurological complications

Several case studies have reported on neurological complications caused by a primary Epstein-Barr virus (EBV) infection. We aimed to investigate the viral loads and the clinical and inflammatory characteristics of this disease entity. We evaluated all 84 cases in which the EBV polymerase chain reaction test (PCR) was requested on cerebrospinal fluid (CSF) for the period 2003-2008. Fourteen patients with proven neuroborreliosis served as the control group. Nine patients were diagnosed with a primary EBV infection and neurological symptoms (median age 36 y; 4 male). Viral DNA copies in CSF were detected by PCR in 7 of 9 patients. The presenting symptoms were meningeal signs, epileptic insults, polyradiculomyelitis, polyradiculitis, and/or sudden cognitive disorders. All EBV cases had a pleocytosis with significantly increased mononuclear leukocytes as compared to the neuroborreliosis group (median 99% interquartile range (96-100%) versus 90% (86-97%). In cases with a primary EBV infection, viral loads ranged from 43 to 3202 copies/ml in CSF and from 61 to 15,595 copies/ml in serum. Seventy-eight percent of the cases had a positive PCR on CSF. This study provides criteria for diagnosing neurological disease during primary EBV infection. Primary EBV infections in immune competent persons can cause a broad range of neurological symptoms, with lymphocytic and monocytic inflammation both in blood and CSF.     

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan

Aim: Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH. Methods: We assessed clinical characteristics and therapeutic processes in 67 patients diagnosed with AIH. Results: Twenty patients (29.9%) suffered from relapses during tapering of corticosteroid therapy. The remaining 47 patients sustained their remission. At the onset of disease, risk factors associated with relapse were: age of 50 years or older; total bilirubin of 1.5 mg/dL or more; aspartate aminotransferase levels of 250 IU/L or more; alanine aminotransferase levels of 250 IU/L or more; prothrombin activity of 80% or more; γ‐globulin levels of 3.4 g/dL or more; and International Autoimmune Hepatitis Group (IAIHG) score of 17 or more in univariate analysis. Grading of histological interface hepatitis is not significantly associated with relapse. Multivariate analysis revealed that IAIHG scores of 17 or more were significantly associated with relapse (odds ratio = 6.57, 95% confidence interval = 1.19–36.33). Seven patients who relapsed were treated with AZP and prednisolone (PSL), and all sustained remission (100%). Of the remaining 13 relapse patients who received only PSL, eight (61.5%) suffered additional relapses. Conclusion: Our results demonstrate the risk factors associated with relapse of AIH. We also show that early administration of AZP after the first relapse may help to prevent additional relapses.     

Low serum level of hepatitis B core-related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy

Aim: The clinical significance of hepatitis B virus (HBV) core-related antigen (HBcrAg) in predicting the reactivation of hepatitis after halting lamivudine administration was analyzed. Methods: A total of 34 patients with chronic hepatitis B were enrolled. Lamivudine was administered for at least 6 months before cessation, and reactivation of hepatitis was defined as elevation of alanine aminotransferase levels to more than 80 IU/L within 12 months of cessation. Results: In total, 20 (59%) patients experienced hepatitis reactivation. Although concentrations of HBV DNA and HBcrAg in serum did not differ between the two groups of patients at the onset of lamivudine administration, HBcrAg serum levels were significantly higher (P = 0.009) in the reactivation patients (median 4.9, 25-75% range 4.7- 5.9 log unit/mL) than the non-reactivation patients (median 3.2, 25-75% range <3.0-4.5 log unit/mL) post-lamivudine treatment. The concentration of HBV DNA did not differ between the two groups (median <3.7, 25-75% range <3.7-<3.7 log copy/mL in the reactivation group vs. median <3.7, 25-75% range <3.7-<3.7 log copy/mL in the non- reactivation group). Receiver operating characteristic analysis of HBcrAg concentration showed an area under the curve of 0.764 in predicting patients without reactivation of hepatitis. Conclusion: HBcrAg can be a useful marker to identify patients who are not at risk of reactivation of severe hepatitis after discontinuation of lamivudine administration.     

Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia

BACKGROUND: Unconjugated hyperbilirubinemia results from Gilbert syndrome and from antiretroviral therapy (ART) containing protease inhibitors. An understanding of the interaction between genetic predisposition and ART may help to identify individuals at highest risk for developing jaundice. METHODS: We quantified the contribution of UGT1A1*28 and ART to hyperbilirubinemia by longitudinally modeling 1386 total bilirubin levels in 96 human immunodeficiency virus (HIV)-infected individuals during a median of 6 years. RESULTS: The estimated average bilirubin level was 8.8 micromol/L (0.51 mg/dL). Atazanavir increased bilirubin levels by 15 mu mol/L (0.87 mg/dL), and indinavir increased bilirubin levels by 8 micromol/L (0.46 mg/dL). Ritonavir, lopinavir, saquinavir, and nelfinavir had no or minimal effect on bilirubin levels. Homozygous UGT1A1*28 increased bilirubin levels by 5.2 micromol/L (0.3 mg/dL). As a consequence, 67% of individuals homozygous for UGT1A1*28 and receiving atazanavir or indinavir had > or =2 episodes of hyperbilirubinemia in the jaundice range (>43 micromol/L [>2.5 mg/dL]), versus 7% of those with the common allele and not receiving either of those protease inhibitors (P<.001). Efavirenz resulted in decreased bilirubin levels, which is consistent with the induction of UDP-glucuronosyltransferase 1A1. CONCLUSIONS: Genotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice.     

Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients

PURPOSE: Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. METHODS: We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. RESULTS: Aminotransferase levels were abnormal in 35% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 +/- 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. CONCLUSION: Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea.     

Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels

BACKGROUND: Natural history studies of hepatitis B virus infection have shown relapse of hepatitis in 5% to 15% of patients and progression to cirrhosis in 2% to 6% annually. Follow-up of patients beginning at the early phase of infection might provide data with less referral bias than in previous studies. METHODS: Test of liver biochemistry, assessment of virological markers, and ultrasound examinations were performed at regular intervals during the course of hepatitis B e antigen (HBeAg) to antibody (anti-HBe) seroconversion in 240 HBeAg carriers with normal alanine aminotransferase levels at baseline. Factors predictive of cirrhosis were identified by multivariate analysis. RESULTS: We enrolled 130 men and 110 women. The mean (+/- SD) age at entry was 27.6 +/- 6.2 years. During the HBeAg-positive phase, 29% of patients had alanine aminotransferase levels > or =200 U/L, 3% had bilirubin levels > or =2.0 mg/dL, and 5% had two or more episodes of alanine aminotransferase levels > or =200 U/L. The mean age at anti-HBe seroconversion was 31.3 +/- 7.0 years, with remission of hepatitis in all patients. However, hepatitis recurred in 36 patients (15%), with an annual rate of 2.2%. Thirteen patients (5%) progressed to cirrhosis. The annual incidence of cirrhosis was 0.5%, and the cumulative probability of cirrhosis after 17 years was 12.6%. Age at anti-HBe seroconversion and relapse of hepatitis were independent risk factors for cirrhosis. CONCLUSION: The clinical severity of chronic hepatitis B was milder in this cohort than in previous studies. Delayed HBeAg seroconversion and relapse of hepatitis were associated with increased risk of cirrhosis.     

Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto-antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.     

Clinical characterization of patients developing histologically‐proven fibrosing cholestatic hepatitis C post‐liver transplantation

Aim: Fibrosing cholestatic hepatitis C (FCH) post‐liver transplantation (LT) is an uncommon disorder with extremely poor outcome. Using stringent histological criteria, we sought to identify cases of FCH to better characterize its incidence, clinical features and outcomes. Methods: From January 1991 to December 2007, 973 LT for hepatitis C virus (HCV) were performed at our center. Using the pathology database, 51 cases with a provisional diagnosis of FCH were identified. FCH was diagnosed histologically by cholestasis accompanied by thin periportal fibrous septa, ductular reaction and mild inflammation. Results: FCH was reconfirmed in 24 recipients; seven had concurrent biliary problems. Twenty‐seven cases were excluded; biopsy was unavailable in nine cases, 15 did not meet the histological criteria of FCH and three had missing clinical information. All received deceased donors at a mean age of 64.4 years (15/17 aged >50 years). Mean time from LT to FCH was 7.6 months with 16 of 17 diagnosed within 1 year of LT. At diagnosis, mean viral load was 14.4 million IU/mL, bilirubin 16.2 mg/dL, aspartate aminotransferase 262 IU/mL, alanine aminotransferase 192 IU/mL and alkaline phosphatase 299 IU/mL. All 17 patients died or required re‐LT a mean of 7.8 months after the FCH diagnosis. Conclusion: FCH occurs infrequently and is typified by hyperbilirubinemia, donor age of more than 50 years, extremely high HCV RNA and specific histological changes occurring within the first several months post‐LT with extremely poor patient and graft survival. Histology alone is not reliable for the diagnosis of FCH, especially in the setting of recurrent HCV with concurrent biliary problems.