Ken Flora

Musculoskeletal pain and fatigue are associated with chronic hepatitis C: A report of 239 hepatology clinic patients

Abstract OBJECTIVE: The aim of this study was to identify the frequency of fatigue and musculoskeletal pain in hepatitis C compared with other liver diseases. METHODS: Hepatology outpatients were evaluated by questionnaire for musculoskeletal pain and fatigue. Charts were reviewed for diagnoses, aminotransferases, histology, treatment, and presence of hepatitis C by second generation ELISA and/or polymerase chain reaction. The frequency of symptoms in patients with and without hepatitis C were compared. RESULTS: In 239 patients (mean age 46.7 ± 11.6 yr; 52% male) musculoskeletal pain was present in 70% for 6.7 ± 8.3 yr and fatigue in 56% for 3.3 ± 5.1 yr. Backache was the most common complaint (54%), followed by morning stiffness (45%), arthralgia (42%), myalgia (38%), neck pain (33%), pain “all over” (21%), and subjective joint swelling (20%). Diffuse body pain was present in 23% on a pain diagram and was strongly associated with fatigue. There was a significant association between hepatitis C positivity and the presence of musculoskeletal pain (81% of HCV-positive compared with 56% of HCV-negative patients, respectively; p = 0.0001), and fatigue (67% compared with 44%; p = 0.001). Musculoskeletal pain was more frequent among patients with isolated hepatitis C infection than among patients with isolated hepatitis B or alcoholic liver disease (91%, 59%, and 48%, respectively; p = 0.004). Similarly, fatigue was more frequent among patients with isolated hepatitis C than among those with isolated alcoholic liver disease or hepatitis B (66%, 30%, and 29%, respectively; p = 0.004). There was no relationship between musculoskeletal complaints and possible route of acquiring hepatitis C, levels of aminotransferases, liver disease severity on biopsy, or interferon treatment. CONCLUSIONS: Musculoskeletal pain and fatigue are frequent in hepatology clinic attendees, particularly those with hepatitis C and are unrelated to severity of liver disease, route of infection, or interferon therapy.

Association of fungal infection and increased mortality in liver transplant recipients

BACKGROUNDnInvasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy.nnnOBJECTIVESnThe aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients.nnnMETHODSnMedical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period.nnnRESULTSnThirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation.nnnCONCLUSIONSnFungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.

Biliary tract complications of side-to-side without T tube versus end-to-end with or without T tube choledochocholedochostomy in liver transplant recipients

BACKGROUNDnBiliary anastomotic complications remain a major cause of morbidity in liver transplant recipients, ranging between 10% and 50% in large clinical series. An end-to-end choledochocholedochostomy with or without T tube (CDCD EE with T tube and CDCD EE w/o T tube) and a Roux-en Y choledochojejunostomy have been standard methods for biliary drainage.nnnMETHODSnThe objectives of this retrospective study were to: (1) evaluate the incidence of biliary tract complications using a new method of side-to-side choledochocholedochostomy without T tube (CDCD SS w/o T tube) and (2) compare the results of CDCD SS w/o T tube with those of CDCD EE with T tube and CDCD EE w/o T tube. From September 1991 through June 1996, 279 orthotopic liver transplants were performed in 268 patients and followed through December 1996 (minimum of 6 months follow-up). A total of 227 CDCD anastomoses in 220 patients were studied (7 retransplants > 30 days): CDCD EE with T tube (n=124), CDCD EE w/o T tube (n=44), and CDCD SS w/o T tube (n=59).nnnRESULTSnSixty-nine biliary complications were observed in 220 patients (30%). Anastomotic and/or T-tube leaks were seen in 43 patients (19%), and anastomotic strictures were found in 26 patients (12%). Forty patients (18%) required percutaneous or endoscopic stent placement (6%) or surgical interventions (12%). CDCD EE with T tube had the highest incidence of biliary leak requiring rehospitalization but the lowest anastomotic stricture and intervention rate and the lowest 6-month mortality rate.nnnCONCLUSIONSnCDCD EE with T tube was superior to CDCD EE or CDCD SS w/o T tube despite the increased number of rehospitalizations. CDCD SS w/o T tube did not offer significant advantages over conventional biliary anastomotic techniques.

Vancomycin-resistant Enterococcus in liver transplant patients

BACKGROUNDnVancomycin-resistant Enterococcus (VRE) infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates.nnnMETHODSnFrom October 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation. Data were collected by patient chart review or from a computerized hospital database.nnnRESULTSnThe 1-year mortality rate with VRE infection was 82%, and with VRE colonization, 7%. This mortality rate contrasts with a 14% 1-year mortality for non-VRE transplant patients (P <0.01, infected patients and colonized patients). Characteristics of VRE colonized and infected patients included recent prior vancomycin (87%), coinfection by other microbial pathogens (74%), recent prior susceptible enterococcal infection (72%), concurrent fungal infection (62%), additional post-OLTx laparotomies (47%), and renal failure (Cr >2.5 mg/dL or need for dialysis; 43%). Biliary complications were seen in 52% of post-OLTx VRE-infected or VRE-colonized patients (versus 22% in non-VRE transplant patients, P <0.05).nnnCONCLUSIONnVRE infection is associated with a very high mortality rate after liver transplantation. The incidence of biliary complications prior to VRE isolation is very high in VRE-infected and VRE-colonized patients. The most common characteristics of VRE patients were recent prior vancomycin use, recent prior susceptible enterococcal infection, coinfection with other microbial pathogens, and concurrent fungal infection. With no proven effective antimicrobial therapy for VRE, stringent infection control measures, including strict and limited use of vancomycin, must be practiced.

Musculoskeletal pain and fatigue are associated with chronic hepatitis C

Objective:The aim of this study was to identify the frequency of fatigue and musculoskeletal pain in hepatitis C compared with other liver diseases.Methods:Hepatology outpatients were evaluated by questionnaire for musculoskeletal pain and fatigue. Charts were reviewed for diagnoses, aminotransferases, histology, treatment, and presence of hepatitis C by second generation ELISA and/or polymerase chain reaction. The frequency of symptoms in patients with and without hepatitis C were compared.Results:In 239 patients (mean age 46.7 ± 11.6 yr; 52% male) musculoskeletal pain was present in 70% for 6.7 ± 8.3 yr and fatigue in 56% for 3.3 ± 5.1 yr. Backache was the most common complaint (54%), followed by morning stiffness (45%), arthralgia (42%), myalgia (38%), neck pain (33%), pain “all over” (21%), and subjective joint swelling (20%). Diffuse body pain was present in 23% on a pain diagram and was strongly associated with fatigue. There was a significant association between hepatitis C positivity and the presence of musculoskeletal pain (81% of HCV-positive compared with 56% of HCV-negative patients, respectively; p= 0.0001), and fatigue (67% compared with 44%; p= 0.001). Musculoskeletal pain was more frequent among patients with isolated hepatitis C infection than among patients with isolated hepatitis B or alcoholic liver disease (91%, 59%, and 48%, respectively; p= 0.004). Similarly, fatigue was more frequent among patients with isolated hepatitis C than among those with isolated alcoholic liver disease or hepatitis B (66%, 30%, and 29%, respectively; p= 0.004). There was no relationship between musculoskeletal complaints and possible route of acquiring hepatitis C, levels of aminotransferases, liver disease severity on biopsy, or interferon treatment.Conclusions:Musculoskeletal pain and fatigue are frequent in hepatology clinic attendees, particularly those with hepatitis C and are unrelated to severity of liver disease, route of infection, or interferon therapy.

Liver transplantation for disulfiram-induced hepatic failure

Fulminant hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram. A patient without a known history of liver disease was transplanted for fulminant hepatic failure secondary to disulfiram. A high index of suspicion and aggressive therapeutic approaches are essential for the prompt diagnosis and treatment of disulfiram-induced hepatic failure. The clinical presentation, histopathology, treatment, and all cases of disulfiram-induced hepatic failure reported in the English literature are reviewed. The role of orthotopic liver transplantation in a case of disulfiram-induced hepatic failure is discussed.

A cautionary note regarding glycyrrhiza (licorice root)

To the Editor: As the use of herbal therapy by patients with chronic liver disease increases, and with the recent publication of excellent reviews pertaining to this subject, concern over the potential toxicities of these agents is appropriately being raised (1, 2). We found it necessary to review the literature pertaining to glycyrrhizin (licorice extract), a substance which has been used for hundreds of years as a traditional remedy for inflammatory diseases. Glycyrrhizin is also being used increasingly by patients with all types of chronic liver disease. Its exact mechanism of action is unknown; however, it appears to have some anti-viral activity, perhaps by induction of interferon (3). It also causes vasoconstriction in peripheral tissues (4), and perhaps of the splanchnic vasculature. In addition, it stimulates the cytochrome P450 system (5). The clinical importance of these activities is unknown.

Complementary and Alternative Treatment of Liver Disease

In the broadest sense, complementary and alternative health treatments encompass health care provided outside the domain of conventional medicine. In the past decade, the proportion of Americans who report using alternative or complementary therapies has grown from 34 to 42%. During that interval, the projected number of total visits to alternative practitioners increased by 47%, from 427 million visits/yr in 1991 to 629 million visits/yr in 1997. It is estimated Americans paid, that year,

Endoscopic ultrasound in cirrhosis: Prevalence of findings in comparison with healthy controls

21.2 for alternative health services, most of which was out-of-pocket expenses (

Transjugular intrahepatic portosystemic shunt patency and the importance of stenosis location in the development of recurrent symptoms.

12.2 billion), an amount comparable to out-of-pocket expenses paid for all U.S. physicians (1,2). With the proliferation of non-conventional health care, patients, providers, and payers have increasingly adopted various forms of alternative therapy, thereby expanding the boundaries of “conventional” medicine. In response to these trends, Congress created the Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH) in 1992, to perform research in complementary, alternative, and unconventional practices. NIH funding for research in alternative medicine has steadily grown, from