Abdul Nadir

Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity

Herbal medicines are gaining widespread popularity. Much of the public believes that botanical herbs are both harmless and useful for the treatment of a variety of symptoms. This belief stands in contrast with the fact that many herbal therapies have been shown to be toxic. In the present case report, cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension. CS is a mixture of ingredients, among which is anthracene glycoside—an herbal agent that previously has been associated with chronic hepatitis. The liver injury in the case herein reported is believed to be related to either anthracene glycoside or one of the other constituents of CS.

Hepatic histopathology and clinical characteristics associated with antiretroviral therapy in Hiv patients without viral hepatitis

Background All available ARV (antiretroviral) agents can cause hepatotoxicity. Many case reports of ARV-induced hepatotoxicity have been described in patients with confounding viral hepatitis. This case series is comprised 23 HIV-positive patients with hepatic enzyme abnormalities but without the evidence of viral hepatitis. The data available for these 23 patients were assessed with an effort to establish any correlation between ARV therapy and abnormal liver function tests (LFTs) as well as the histologic findings on liver biopsies. Methods The 23 participants included in this study were referred to a hepatology/gastrointestinal clinic that catered specifically to HIV patients. The patients were referred by their HIV providers for evaluation of elevated LFTs, gastrointestinal symptoms or cirrhosis. The data surveyed included variables associated with hepatotoxicity and HIV infection. Results Liver biopsies were obtained in 21 out of 23 participants. The remaining two participants had evidence of cirrhosis based on imaging studies. The LFT elevations were definitely or possibly attributed to ARV therapy in 17 out of 23 participants. Specifically, the biochemical hepatotoxicity was definitely related to ARV therapy in six and possibly related to ARV medications in 11 participants. Nine out of 17 participants had evidence of nonalcoholic steatohepatitis, whereas four out of 17 had clinical features of lipodystrophy. Six participants had elevated LFTs before starting ARV therapy. The participants with nonalcoholic fatty liver diseases had normal LFTs for many years after which a steep rise was noted. All participants with nonalcoholic fatty liver diseases were exposed to nucleoside reverse transcriptase inhibitors. Conclusion ARV medications, particularly the nucleoside reverse transcriptase inhibitors, can cause a dose-dependent hepatotoxicity that occurs after several months of exposure and possibly result in increasing the adverse effects of alcohol and obesity. Owing to the overlap of ARV medications, the contribution of each class of drugs toward the observed hepatotoxicity is not entirely clear. Liver biopsies should be considered in patients receiving ARV therapy with elevated LFTs and/or evidence of fatty liver.

Prevalence of risk factors for hepatitis C virus in HIV-infected and HIV/hepatitis C virus-coinfected patients.

Methods: A sample of patients with HIV completed a questionnaire identifying their demographic characteristics and risk factors for hepatitis C virus (HCV). A chart review was conducted to confirm the information obtained using the questionnaire. Risk factors associated with coinfection status at α level of 0.1 in univariate analysis were entered into a multivariate Cox regression model. Results: Of the 242 HIV-positive patients analyzed, 168 were HIV-infected and 74 were HIV/HCV-coinfected. Risk factors that were significantly different between HIV-monoinfected and HIV/HCV-coinfected subjects included intravenous drug use, snorting drugs, sharing razors or toothbrushes, being in prison, the presence of one or more tattoos, sex for money or drugs, sex with an intravenous drug user and man who has sex with men. In a multivariate regression model, only intravenous drug use remained as a significant risk factor/predictor of HCV/HIV coinfection. A subanalysis identified risk factors more prevalent among coinfected men who have sex with men, including intravenous drug use, sharing razors/toothbrushes, tattoos, sex for money or drugs, sex with an intravenous drug user, and a history of having 11 or more sexual partners. A history of having had a sexually transmitted disease and 11 or more sex partners was more prevalent among HIV-monoinfected men who have sex with men. Conclusions: HIV/HCV coinfection was associated with intravenous drug use but not with sexual risk factors.

Cryoglobulinemia: a cause for false negative polymerase chain reaction results in patients with hepatitis C virus positive chronic liver disease

With the introduction of interferon therapy for liver disease due to chronic viral hepatitis, it has become important to test individuals thought to have hepatitis C virus disease for the presence of the virus. Moreover, the current goal of therapy for hepatitis C virus-positive liver disease is to render the individual patient HCV-RNA negative. Recently, it has been reported that as many as one-third of the patients with hepatitis C virus liver disease test positive for the presence of mixed cryoglobulins. Few of these cryoglobulin-positive patients have overt disease manifestations of cryoglobulinemia, such as nephropathy, peripheral neuropathy and vasculitis. Because the cryoglobulins in patients with hepatitis C virus-positive disease are directed at hepatitis C virus epitopes, the precipitation of cryoglobulins from serum samples also effectively removes virus. When the viral carriage rate is low in terms of the number of genomes/unit serum, as occurs in cases that are partially treated, the serum can test negative for hepatitis C virus even by polymerase chain reaction, despite the presence of persistent viremia, if precautions preventing the precipitation of cryoglobulins prior to the removal of the sample for polymerase chain reaction testing are taken. From a group of 75 patients with hepatitis C virus-positive hepatitis seen at our institution in the last year (all HCV-RNA positive), 35% were found to test positive for the presence of cryoglobulins. Importantly, in all cases, the cryoglobulins collected tested strongly positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver transplantation for fulminant hepatic failure.

The etiology and prognosis of individuals with various forms of fulminant hepatic failure are reviewed. Special techniques of clinical management and decision making as to when and to whom to transplant in cases of fulminant hepatic failure are reviewed.

A Comparison of Risk Factors for HCV-mono-infection, HIV-mono-infection, and HCV/HIV-co-infection in a Community Setting

The prevalence of HIV infection in HCV patients is much lower than the prevalence of HCV infection in HIV patients. Whereas the higher prevalence of HCV infection in HIV is clearly related to drug abuse, the reasons for the lower prevalence of HIV infection in HCV patients has not been reported. The prevalence of non-sexual and sexual risk factors associated with acquisition of hepatitis C and HIV were studied in HIV-mono-infected, HCV-mono-infected, and HCV/HIV-co-infected individuals. None of the 114 HCV-mono-infected patients tested positive for HIV and this finding was associated with a significantly lower number of men who have sex with men (MSM) among the HCV-mono-infected subjects than among either the HIV-mono-infected or HCV/HIV-co-infected individuals. Unprotected anal intercourse and sex for money or drugs were reported less often by HCV-mono-infected individuals than by HIV-mono-infected and HCV/HIV-co-infected subjects. Having sex with an intravenous-drug user (IVDU) was reported more frequently by both HCV-mono-infected and HCV/HIV-co-infected individuals than by HIV-mono-infected individuals. Sub-analysis of the group of MSM revealed that IVDU differentiated between HIV-mono-infected and HCV/HIV-co-infected subjects. These results reveal that the lower prevalence of HIV in HCV patients is related to a lower number of MSM in this group and that sex with an IVDU is a surrogate marker for drug abuse related to acquiring HCV but not HIV. The guidelines should include strategies for testing for HCV and HIV in patients with these infections.

Celiac disease in patients with HCV Genotype 1A

TO THE EDITOR: A 70-yr-old man treated with interferon 2b (INF 2b) for chronic hepatitis C presented with acute rhabdomyolysis. Hepatitis C was diagnosed 6 months previously (confirmed by results of polymerase chain reaction), and liver biopsy showed moderate chronic hepatitis (histological activity index (HAI) 15, fibrosis 2) (1). Treatment with INF 2b (3 MIU three times wk) was started. Two weeks later, he was referred to our unit of Internal Medicine for sudden appearance of fever (38°C), weakness, and acute generalized myalgia. On admission, he denied any antecedent signs of infection, any trauma, and assumption of any other drugs except for INF. General physical examination resulted normal. Laboratory findings showed a marked increase in the concentrations of creatine kinase at 3.641 U/L (normal range 5–70 U/L) with normal concentrations of the isoform creatine kinase-MB (CK-MB), lactate dehydrogenase at 717 U/L (normal range 80–240 U/L). Myoglobinuria was present (88 mg/L). There were no pathological alterations in concentrations of creatinine, urea nitrogen, C-reactive protein, blood cell counts, or glucose. No electrolyte abnormalities were detectable. With the diagnosis of rhabdomyolysis, INF 2b treatment was discontinued. The patient was treated with i.v. fluids and bicarbonate to maintain an alkaline urine output. Within 4 days, fever and myalgia disappeared, and weakness significantly improved; the creatine kinase declined to normal values (101 U/L). At the follow-up visit at 2 and 4 months, the patient was in good condition, and creatine kinase was within the normal range. Rhabdomyolysis has been reported as an unusual adverse reaction to several drugs, in particular in patients treated with statin (2). A few cases of acute rhabdomyolysis associated with INF 2b have been reported. Greenfield et al. described a patient 10 wk after initiation of INF 2b treatment starting with 5 MU three times/wk for chronic active hepatitis C (3). Reinhold et al. recently described a fatal outcome of fulminant rhabdomyolysis with multiple organ failure in a 56-yr-old man receiving adjuvant high-dose INF 2b (20 Mio. 1E m 2 daily) (4). The authors revealed that the manufacturers of INF 2b have received only 11 reports worldwide. Remarkably, the manifestation of muscle injury occurred when the dose of INF 2b was being increased in both patients described, suggesting that rhabdomyolysis represents at least a dose-dependent side effect of this drug. With respect to the previous reports, in our patient, the dosage of INF 2b was unaltered and significantly lower; moreover, the clinical and laboratory alterations were milder, and the recovery of the patient was quite quicker. These findings seem to confirm that muscle injury could be (if rare) a side effect of INF 2b, and to suggest that it may occur also at low doses. INF 2b discontinuation leads to a complete recovery of the disease. Measurement of creatine kinase activity could be recommended after initiation of INF 2b treatment and after every increasing of its dosage to precociously individualize and prevent irreversible rhabdomyolysis.

First Report of Telaprevir-Induced Pancreatitis

We present the first case of telaprevir-induced pancreatitis which is summarized below. A 67-year-old Cambodian male with HTN, HCV genotype 1a/1b and viral load of 130,019 IU moved to the United States in May 2011. He had no history of drug/alcohol abuse or pancreatitis. Lisinopril 10 mg and hydrochlorthiazide (HCTZ) 25 mg daily were initiated. Alkaline phosphatase (AP), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), bilirubin, and platelets were 256 (56–119) IU, 147 (21–72) IU, 125 (27–59) IU, 1.1 (0.2–1.3) mg/day, and 52,000 (140–440) mm, respectively. An abdominal CT scan with contrast showed nodular liver, normal gallbladder and pancreas. No esophageal or gastric varices were seen on endoscopy. Four days after treatment for hepatitis C with subcutaneous peginterferon a2 a 180 mcg weekly, oral ribavirin 1,000 mg daily and oral telaprevir 750 mg three times daily was begun; he developed upper abdominal pain and was admitted with a lipase level of 18,066 (23–300) IU. An abdominal CT scan showed mild peri-pancreatic fat stranding. His AP, ALT, AST and bilirubin were 327, 145, 161 IU and 2 g/dl, respectively. All medications were held, and abdominal pain improved with daily reduction of lipase (Fig. 1). An MRCP showed normal pancreaticobiliary anatomy. A triglyceride level was normal. One day after admission, ribavirin 800 mg was started followed by peginterferon a2 90 mcg 3 days later (8th day after his first injection) without development of abdominal pain. Telaprevir 750 mg TID was started 1 day after peginterferon a2a injection. He received two doses of telapevir on day 1 at 16:14 and 21:06; the following day lipase drawn at 05:43 increased from 3,310 to 3,467 IU, although he reported no abdominal pain. Three more doses at 08:24, 12:35 and 20:45 were given on day 2 and he complained of mild abdominal pain at night which became less in the morning, and the lipase trended down to 2,532 at 05:15. On day 3 he received telaprevir doses at 08:50 and 17:44, but experienced more abdominal pain, and lipase drawn at 16:00 increased to 3,057 IU. Telaprevir was discontinued, abdominal pain improved and lipase trended down to 2,327 IU the next morning. Nine days later, when he was seen in clinic, he reported no abdominal pain and his lipase was 2,177 IU while he was on HCTZ, lisiniopril, peginterferon a2a 180 mcg and ribavirin. Although, erroneously, he was placed on TID dosing of telaprevir, his pancreatitis clearly was exacerbated with telaprevir re-administration. Moreover, his lipase trended down further over 9 days, without development of abdominal pain, while using all other medications he was on before. The patient was lost to follow up and we could not document further decline of lipase. Interferon, HCTZ, lisinopril, and ribavirin have been reported to cause pancreatitis [1–5]. This is likely an idiosyncratic reaction of telaprevir, and pancreatitis should be considered in a patient presenting with abdominal symptoms. C. Ventura R. Urich S. Skinner R. Bina K.-Y. Chuang D. H. Van Thiel A. Nadir (&) Maricopa Medical Center, 2601 E Roosevelt Street, Phoenix, AZ 85008, USA e-mail: anadir786@aol.com

Occurrence of Jaundice Following Simultaneous Ursodeoxycholic Acid Cessation and Obeticholic Acid Initiation

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease for which ursodeoxycholic acid (UDCA) has been the mainstay of treatment. Obeticholic acid (OCA) emerged in 2016 as a second agent for PBC treatment. It is indicated for use in combination with UDCA in patients who have had an inadequate response to UDCA, or as sole treatment in adults unable to tolerate UDCA. Intriguingly, OCA has been reported to induce dose-dependent jaundice, despite the fact that it reduces bile acid synthesis and improves bile flow [1]. Herein we report a case of severe jaundice that occurred in a PBC patient 8 weeks after abrupt cessation of UDCA and simultaneous initiation of OCA therapy.

Are Endoclips Best Approach to Cannulate an Ampulla Hidden in the Duodenal Diverticulum

Dear Editor, Recently, we performed an ERCP on a patient with the ampullary opening located within a large diverticulum and would like to comment on a similar case reported by Cappell et al. [1] in your journal. A 57-year-old Caucasian male presented with upper abdominal pain and elevated liver enzymes (ALT 58 IU, AST 55 IU, Alkaline phosphatase 162 IU and total bilirubin of 2.0 mg/dl. Abdominal CT scan revealed a 2.5 cm common bile duct (CBD) with a calcified filling defect suggestive of a stone. During the ERCP, we noted an inverted ampulla located in the lateral, superior rim of a large duodenal diverticulum (Fig. 1). As our initial attempts to bring the ampulla en face using a sphincterotome (44 Fr, Boston Scientific) were not successful, an endoclip (Boston Scientific) was placed laterally to the ampulla to evert the ampulla out of the diverticulum (Fig. 2). As the ampullary opening was still not in a good position for cannulation, a second clip was deployed over the duodenal fold superior to the ampulla to stabilize the everted ampulla. This resulted in the instability of the ampulla and the downward rotation of the ampullary opening into the diverticulum (Fig. 3). Fortunately, we were able to evert the ampullary opening out again using the sphincterotome, and during a moment of ampullary stability, the biliary opening was cannulated. The ampulla then was stabilized with a guidewire advanced into the CBD (Fig. 4). A biliary sphincterotomy was performed over the guidewire, followed by the placement of a 7 Fr 9 10 cm plastic biliary stent (Boston Scientific). The CBD stone removal was deferred for the future, considering the length of the procedure. In contrast to the favorable experience reported by Cappell et al., our case highlights that endoclip placement to facilitate biliary cannulation within a duodenal diverticulum might make the ampullary opening more unstable