Editorial
Livline
Liver is vulnerable to hepatic
damage as it is exposed to both
the parent drug entering from
the gastrointestinal tract and to
the metabolites produced after
biotransformation of the drug. A
high dosage of the drug can result in
the loss of enzyme specificity, which
in turn leads to abnormal drug
metabolism. Drugs can interfere
with bilirubin transport, cause
damage to hepatic parenchyma,
and result in cholestasis, fatty liver,
and liver failure. Drugs account
for 20% to 40% of all instances
of fulminant hepatic failure
and approximately 75% of the
idiosyncratic drug reactions result
in liver transplantation or death.
This issue focuses on “drug-
induced hepatitis.” In line with
this theme, we have featured an
article on hepatotoxicity associated
with statins in the “Research
update” section. The “Clinical
review” section features a clinical
trial report that emphasizes the
protective effect of Liv.52 DS
tablet against statin-induced liver
damage. In “Expert comments,”
Dr Nanda Ganpat Dhavale shares
her experience of treating patients
with drug-induced hepatitis with
Liv.52 DS.
We hope you find the articles
of this issue interesting and
informative. We welcome your
feedback and suggestions. Please
write to us at publications@
himalayahealthcare.com.
Happy reading!
— Editor
Drug-induced
This Issue
Hepatitis
Contents
page
2 • Clinical review
• Drug alert
page
3
• News wise
• Expert comments
• Herb facts
page
4
• Laugh lines
• Liv-wise
A Publication of The Himalaya Drug Company
Research update
Hepatotoxicity Associated With Statins:
Reports of Idiosyncratic Liver Injury Post-marketing
Bjornsson E, et al
J Hepatol. 2012;56(2):374–380.
Abstract
Limited data exist on drug-induced liver injury (DILI) associated with
statins. Reports on adverse reactions suspected to be due to statins received
by the Swedish Adverse Drug Reactions Advisory Committee (SADRAC)
1988–2010 were analyzed.
The most common types of adverse drug reactions (ADRs) suspected
were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had
at least possible relationship, median age 64 years (57–73), 55% males,
whereas 25/124 cases (20%) were excluded due to mild elevations of liver
tests and 26 due to unlikely relationship and/or lack of data. A statin-
related DILI episode was reported in 1.2/100,000 users. Atorvastatin was
implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin in
15%, and others. Two patients died of acute liver failure, one underwent
liver transplantation and 25 (34%) had jaundice. Three patients were
rechallenged with the same statin producing similar patterns of liver injury.
The median duration of therapy was 90 days (30–120), 120 (39–248) for
atorvastatin, and 75 (30–150) for simvastatin (NS). Cholestatic/mixed
injury was more common with atorvastatin, 17/30 (56%) than with
simvastatin, 7/28 (24%) (P = .018).
Idiosyncratic liver injury associated with statins is rare but can be
severe. After recovery, a similar pattern of liver injury can be reproduced
on re-exposure. Most patients experience liver injury 3 to 4 months after
the start of therapy. Atorvastatin is mostly associated with cholestatic liver
injury whereas hepatocellular injury is more common with simvastatin.
Introduction
Although most trials assessing the cardiovascular efficacy of statins
and their safety have included a large number of patients, they have been
underpowered to detect clinically relevant drug-induced liver injury
(DILI). It is well-known that idiosyncratic DILI associated with drugs is
generally detected in the post-marketing phase. It has been convincingly
shown that the risk of developing statin-induced liver injury is not related
to the presence of pre-existing liver abnormalities, mostly nonalcoholic
fatty liver disease (NAFLD). On the contrary, the use of statins has been
shown to be associated with improvement in liver test abnormalities and
histologies in patients with NAFLD. The existence of statin-induced
hepatotoxicity has been put into question and called a “myth”. A systematic
assessment of DILI of these widely used drugs is largely lacking.
Aim
This study was aimed to analyze the proportion of DILI suspected
to be due to statins out of all adverse reactions reported for this type of
drugs, and to characterize the type of liver injury and clinical outcome.
Furthermore, the incidence of liver injury in patients on statins based on
spontaneous reporting and market sales figures of statins during the study
period was calculated.
Materials and Methods
All reports of suspected adverse drug reactions (ADRs) received by
the Swedish Adverse Drug Reactions Advisory Committee (SADRAC)
from 1970 have been computerized and made available for analysis. Full
medical records, including laboratory results and imaging studies are
requested for the majority of serious and all fatal cases. All cases reported
to SADRAC, suspected to be due to statins since these drugs were put
on market, were retrieved. Only cases with DILI reported to SADRAC
were reviewed. Medical records and results of laboratory data, duration of
treatment, exclusion of competing causes, and clinical outcomes such as
potential death from the drug reaction and/or liver transplantation due to
DILI were analyzed. Only cases with > 5 × upper limit of normal (ULN) in
aminotransferases and/or alkaline phosphatase > 2 × ULN were included.
Vol. 9 • No. 1 • Jul–Sep 2014
Only for reference by a registered medical
practitioner, hospital, or laboratory
Liv.52
®
– Unparalleled in liver care
Results and Discussions
The first statin drug was marketed in Sweden in 1988. During the
period from 1988 to November 2010, SADRAC received a total of 239
reports of adverse effects suspected to be due to statins. Twenty-two
of the 239 (9.2%) cases were considered by SADRAC to be of unlikely
relationship whereas 217 had a possible causality according to SADRAC.
The most common types of ADRs suspected were DILI in 124/217 (57%)
reports, rhabdomyolysis/myalgia in 42/217 (19%), pancreatitis (5%),
dermatological (4.3%), gastrointestinal (4.3%), neurological (3.3%),
and urinary (2.9%) side-effects. Out of 124 reports considered to be
potentially related to the statin therapy, 51 (41%) cases were excluded, 26
due to insufficient information making a causality assessment according
to RUCAM impossible, whereas in the remaining cases, elevation of
aminotransferases (AST and/or ALT) was < 5 times ULN as well as ALP
< 2 x ULN. Thus, a total of 73 cases were included in the final analysis.
Two patients died and 1 underwent liver transplantation associated
with statin therapy. Three other patients were rechallenged with the same
statin, which produced a similar pattern of liver injury as experienced
by the patients during the first liver injury associated with the statin
treatment. This occurred approximately 1 month after the start of the re-
exposure. The rechallenge was in these cases inadvertent, as the responsible
physicians were either not certain whether the previous liver injury was due
to the statin (n = 2) or did not take the previous liver reaction seriously. All
these patients had a very thorough diagnostic work up. None had suspicion
of alcoholic liver disease, viral markers for a recent infection with hepatitis
A, B, C, cytomegalovirus, and Epstein-Barr virus were negative, and none
had suffered from hypotension prior to the reaction.
According to the causality assessment, 52 (71%) patients had a possible
relationship, 14 (19%) probable, and 7 (10%) highly probable. In the
total study cohort, a total of 43 (59%) patients were of hepatocellular
type, 22 (30%) were of cholestatic type, and 8 (11%) were of mixed type.
The vast majority of reports of statin-induced hepatotoxicity were due
to atorvastatin (n = 30) and simvastatin (n = 28). Other statin-associated
liver injuries were due to fluvastatin (n = 11), pravastatin (n = 2), and
rosuvastatin (n = 2).
The majority of patients (55%) were males and the median time
from the start of the statin treatment until abnormal liver tests detected
was 3 months. Approximately 35% had jaundice at presentation and the
median ALT elevation was 10 × ULN. In a total of 5 cases, information was
available about a switch to another statin after recovery of liver tests. This
was possible in all cases without elevation of liver tests while on therapy
(with more than 3 months of follow up in all). In 3 patients, atorvastatin
was replaced by pravastatin (n = 2) and in 1 by simvastatin. Two patients
with rosuvastatin-induced liver injury were able to use simvastatin and
atorvastatin, respectively.
Duration of treatment tended to be longer with atorvastatin compared
to simvastatin (approximately 4 vs 3 months) in patients suffering from
liver injury. A significantly higher proportion of patients on atorvastatin
had cholestatic/mixed type of liver injury compared with those treated with
simvastatin. Otherwise, no significant differences were revealed between
the 2 groups.
In 19/73 (26%) cases, another drug was discontinued together with
statin. The other drugs implicated were cefadroxil, celecoxib, ciprofloxacin,
daltaparin, estrogen, isoniazid, losartan, metformin, mexitil, nefazodon,
amlodipine, enalapril (n = 3), rofecoxib, sertraline, ticlopidine, and
lisinopril. Some of these drugs interact with the metabolism of simvastatin
and atorvastatin through the cytochrome P450 isoenzyme CYP3A4. The
interaction is either by inhibition of the isoenzyme or by competition
for the enzyme. However, no clinically relevant interactions were found
Contd on page 4 ...
Livline • Vol. 9 • No. 1 • Jul–Sep 2014

Clinical review

Evaluation of Liv.52®DS Tablet as a Hepatoprotective

Agent in Prophylaxis With Statin Therapy
Das JKL
Med Update. 2007;15(7):31–36.

Background bilirubin from 0.800 ± 0.026 to 1.022 ± 0.077. In the group

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors (statins) are the most commonly prescribed
classes of medications for dyslipidemia. Statins can cause liver
damage in the form of increasing transaminase levels.
Aim
This study was conducted to evaluate Liv.52 DS tablet as a
hepatoprotective agent in prophylaxis with statin therapy.
Methods
This study was an open clinical trial, conducted as per the
ethical guidelines of the Declaration of Helsinki. All patients
on antihyperlipidemic therapy with statins were included in
the study. Pregnant women and patients having evidence of
extensive disease that required hospitalization were excluded
from the study.
A total of 50 patients were enrolled into the trial and all
patients completed the study. Patients were divided into 2
equal groups of 25 each; one group received Liv.52 DS tablet +
atorvastatin tablet, while the second group received atorvastatin
tablet alone. Patients in the former group were advised to take
Liv.52 DS tablet at a dosage of 1 tablet BID and atorvastatin
10 mg, 1 tablet BID for 3 months.
A thorough history, symptomatic evaluation, and clinical
examination were done for all patients before treatment and
during follow-up visits every week for 3 months. Liver function
tests, hemogram, and other biochemical tests were done at
the end of first, second, and third month of treatment. The
predefined primary endpoints were clinical and laboratory
evidence of normal functioning of liver.
Results
In the group that received atorvastatin alone, there was a
significant increase (P < .01) in the mean values of serum
glutamic pyruvic transaminase (SGPT) from 45.87 ± 4.98
to 102.70 ± 12.05, serum glutamic oxaloacetic transaminase
(SGOT) from 42.70 ± 4.74 to 98.87 ± 12.35, and total
receiving Liv.52 DS tablet + atorvastatin, after 3 months,
no such increases in SGPT, SGOT, and total bilirubin were
observed. Figure 1 represents the comparison of SGPT levels
between Liv.52 DS tablet + atorvastatin and atorvastatin-alone
groups.
Figure 1. Comparison of SGPT Levels in Liv.52 DS + Atorvastatin and
Atorvastatin-alone Groups
SGPT, serum glutamic pyruvic transaminase
There were no significant differences between the groups
in terms of physical examination like skin, general state,
temperature, liver size, and weight; and subjective signs like
coating of the tongue, loss of appetite, nausea, vomiting,
and pain and discomfort in the right hypochondrium. No
significant differences were noticed in the other biochemical
and hematological parameters between the groups.
Conclusion
Thus, this clinical study proves that Liv.52 DS tablet has
hepatoprotective effect against statin-induced liver damage.
Drug alert
Liver Enzyme Abnormalities During
Antipsychotic Treatment: A Case
Report of Risperidone-associated
Hepatotoxicity
López-Torres E, et al
Drug Metabol Drug Interact. March 6, 2014 (doi: 10.1515/dmdi-
2013-0064).
Drug-induced liver enzyme abnormalities may indicate
hepatic injury. Antipsychotic drugs also may cause increase
in the liver enzymes and serum bilirubin levels. The present
report evaluates the case of a patient with risperidone-
associated hepatocellular damage. A 19-year-old Caucasian
man was admitted to the Department of Psychiatry with
paranoid schizophrenia and risperidone was administered in
a gradually increasing dose up to 8 mg/day. After 3 weeks
of treatment, he experienced asthenia and weight loss.
The level of aspartate aminotransferase was 283 IU/L
(normal level < 30 IU/L), and the alanine aminotransferase
(ALT) level was 778 IU/L (normal level < 36 IU/L).
Treatment with risperidone was immediately discontinued.
Six days after drug withdrawal, the ALT level fell more than
50%, and a complete return to normalcy was seen within
2 months.
In this case, a possible causal association between
risperidone and hepatocellular damage has been observed
due to the temporal relationship between the administration
of the drug and the onset of hepatic abnormalities, and a
following rapid recovery after stopping the drug. As the
hepatic damage could be related to the plasma concentration
of risperidone, which is highly influenced by the hepatic
enzyme CYP2D6, the patient was genotyped for CYP2D6.
He was classified as homozygous wild type for CYP2D6.
The risk for developing hepatotoxicity during
risperidone therapy cannot be supported by the patient’s
CYP2D6 genotype. In clinical practice, it may be
recommended to obtain baseline liver function tests before
starting risperidone and regular screening for liver enzyme
changes during therapy.

Therapy of Toxemias of Pregnancy

Narone JN, Narone R
Probe. 1972;XI(2):120–122.

Background and Objective
Pregnancy is a natural physiological process, which
involves a strain on all systems of the body as well as on all
the important excretory functions. A drug that would keep
the liver functioning at its optimum in spite of various factors
predisposing toward liver damage like malnutrition, toxemias,
industrial toxins, toxic action of drugs and alcohol would be of
great use.
This study was conducted to evaluate the effect of Liv.52
tablets on various toxemias of pregnancy.
Methods
This study was conducted on 35 pregnant women in the
age range of 21 to 35. The patients belonged to various groups
based on the symptoms shown.
There were 10 cases of preeclampsia, who suffered from appetite and disappearance of vomiting symptoms. Out of 10
albuminuria, headache especially of the frontal variety and anemic patients, 8 showed very good response and 2 showed
flashes before the eyes or disturbance of vision. Their ages fair responses. In preeclamptic toxemia cases, the results of
ranged from 28 to 35 years. Four showed marked edema of feet, therapy were fair in 8 cases and good in 2 cases. Three out of
4 patients with hyperemesis gravidarum responded very well
2 had stomatitis, 2 had generalized fits, and appetite was poor
in most of the cases. All showed typical signs and symptoms to the therapy. In the patient suffering from jaundice with
enlarged tender liver, upon treatment with Liv.52 tablets, the
of preeclampsia. In 6 patients, systolic blood pressure was
appetite improved, liver tenderness disappeared, and the liver
between 160 and 180 mm Hg and in 1 patient, 150 mm Hg.
receded to the costal margin showing a very good response.
The diastolic blood pressure was between 100 and 120 mm Hg
Table 1 shows Liv.52 treatment results in various toxemias of
in all these cases. pregnancy.
There were 4 cases of hyperemesis gravidarum between
the ages of 23 and 28 years. There was marked continuous Table 1. Effect of Liv.52 Treatment in Various Toxemias of Pregnancy
vomiting in all of them, which lasted for some time. Effect of Liv.52 Treatment
Toxemia of Pregnancy
Good Fair Poor Total
In a second-para (P2) woman in the 26th week of
Vomiting in First
pregnancy, the liver was enlarged to 3.5 cm in the midclavicular Trimester
10 Nil Nil 10

There were 10 cases of vomiting in the first trimester, line and was tender with jaundice. Severe Anemia of
8 2 Nil 10
Pregnancy
varying in age range from 21 to 30 years. All the 35 patients were administered Liv.52 tablets at a Preeclamptic Toxemia 8 2 Nil 10
There were 10 cases of severe anemia where toxemia and dosage of 2 tablets TID for at least 3 weeks and the progress Hyperemesis Gravidarum 3 1 Nil 4
disturbed liver function played a role. The percentage of and results were recorded. Jaundice in Enlarged
1 Nil Nil 1
Tender Liver
hemoglobin was between 20% and 30% in 4 cases, between
30% and 40% in 3 cases, and between 30% and 50% in Results Total 30 5 Nil 35

the other 3 cases. The patients had poor appetite, mild Patients showed a positive response toward treatment.
constipation, and occasional heartburn. Their ages ranged from Good response was observed 85.6% and fair in 14.4% cases. Conclusion
20 to 32 years. The period of pregnancy ranged from 28th to In patients with vomiting in the first trimester, continuous From the results it can be concluded that Liv.52 is effective
38th week and most of them were normal in weight. therapy with Liv.52 tablet for 2 weeks lead to improvement of in the management of various toxemias related to pregnancy.

2
Livline • Vol. 9 • No. 1 • Jul–Sep 2014
News wise
Hepatitis C Virus Co-infection Increases
the Risk of Anti-tuberculosis Drug-
induced Hepatotoxicity Among Patients
With Pulmonary Tuberculosis
Lomtadze N, et al
PLoS One. 2013;8(12):e83892.
The country of Georgia has a high prevalence of
tuberculosis (TB) and hepatitis C virus (HCV) infection. This
study was undertaken to determine whether HCV coinfection
increases the risk of incident drug-induced hepatitis among
patients on first-line anti-TB drug therapy.
In this prospective cohort study, HCV serology was
obtained on all study participants at the time of TB diagnosis.
Hepatic enzyme tests (serum alanine aminotransferase [ALT]
activity) were also obtained at baseline and monthly intervals
during the treatment.
Among 326 study patients with culture-confirmed TB, 68
(21%) were HCV coinfected, 14 (4.3%) had chronic hepatitis
B virus (HBV) infection (HBV surface antigen positive
[HBsAg+]), and 6 (1.8%) were HIV coinfected. Overall, 19%
of patients with TB developed mild to moderate incident
hepatotoxicity. In multi-variable analysis, HCV coinfection
(adjusted hazards ratio [aHR] = 3.2; 95% CI = 1.6–6.5) was
found to be an independent risk factor for incident anti-TB
drug-induced hepatotoxicity. Survival analysis showed that
HCV coinfected patients developed hepatitis more quickly
compared to HCV seronegative patients with TB.
A high prevalence of HCV coinfection was found among
patients with TB in Georgia. Drug-induced hepatotoxicity was
significantly associated with HCV coinfection but severe drug-
induced hepatotoxicity (WHO grade III or IV) was rare.
Expert comments
Interview with Dr Nanda Ganpat Dhavale
Drug-induced Hepatitis
Which are the drugs that can lead to drug-induced
hepatitis?
Generally, hepatotoxic drugs like antitubercular (anti-TB)
drugs and statins are responsible for drug-induced hepatitis
(DIH). Both anti-TB drugs and statins can cause varied
degree of hepatotoxicity from a transitory asymptomatic
rise in transaminases to acute liver failure. Patients receiving
anti-TB drugs frequently develop acute or chronic hepatitis.
Recent studies showed that genetic polymorphisms of
N-acetyltransferase 2 and glutathione-S-transferase are the
major susceptibility factors for anti-TB DIH.
The time required for the metabolites to reach hepatotoxic
levels is much earlier with isoniazid + rifampicin treatment
than isoniazid-alone treatment and this has been shown
to be synergistic rather than additive. Drugs containing
acetaminophen such as analgesics, antipyretics, and
nonsteroidal anti-inflammatory drugs such as ibuprofen and
naproxen are also known to cause DIH.
How is DIH diagnosed?
Clinically, DIH can be suspected when a patient presents
with nausea, vomiting, abdominal pain, dark urine, diarrhea,
fatigue, fever, headache, jaundice, loss of appetite, rash,
and white or clay-colored stools. Diagnosis of DIH can be
made by performing different screening methods, such as,
determination of serum bilirubin level, determination of
aminotransferases and alkaline phosphatase enzymes activities,
assessment of antinuclear antibodies, copper and iron levels,
virological screening, abdominal ultrasound, CT or MRI scan,
and liver biopsy.
If DIH is suspected and confirmed, the physician has
to report the findings to the FDA and the pharmaceutical
manufacturer.
How common are the cases of DIH in clinical practice?
Cases of DIH are quite common, especially with the usage
of anti-TB drugs and statins. Doctors can prevent DIH to a
Eating Disorders Symptoms in
Pregnancy and Postpartum:
A Prospective Study in a
Disadvantaged Population in Brazil
Angélica Nunes M, et al
Int J Eat Disord. 2014;47(4):426–430.
This study was conducted to assess eating disorder
symptoms (EDS) from prepregancy through postpartum.
Seven hundred and twelve women with gestational
age ranging from 16th to 36th week completed the
eating disorder examination questionnaire (EDE-Q).
A shortened version of the EDE-Q was used to assess,
retrospectively, EDS during the last 28 days of the
pregestational period. Follow-up assessment occurred at
fourth to fifth month postpartum (n = 427). Generalized
structural equation models were used to estimate risk of
EDS in pregestation, gestation, and postpartum.
Women who did not participate in follow up (n =
285) were not significantly different in sociodemographic
characteristics. In postpartum, a higher number of
women referred shape (RR = 1.65, 95% CI = 1.19–2.30)
and weight concerns (RR = 1.64, 95% CI = 1.16–2.31)
than in pregestation. Binge eating (BE) and self-induced
vomiting diminished during pregnancy (RR  = 
0.70,
95% CI = 0.57–0.85; RR = 0.21, 95% CI = 0.10–0.44,
respectively) and postpartum (RR = 0.62, 95% CI =
0.48–0.80; RR = 0.38, 95% CI = 0.19–0.76, respectively)
compared with pregestation.
Shape and weight concerns are highly prevalent in
postpartum and may confer risk for the development
of inappropriate eating behaviors. Health professionals
should be trained on how to recognize these symptoms.
Dr Nanda Ganpat Dhavale, MD
Medical Superintendent
Aundh Chest Hospital
Pune 411027, Maharashtra
India
great extent by prescribing these drugs judiciously and adding
hepatoprotective drugs to the patient’s treatment regimen.
Besides anti-TB drugs and statin-induced hepatitis, about 10%
acute hepatitis cases are due to over-the-counter drug abuse.
Have you prescribed Liv.52 DS for the treatment of DIH?
Yes, I often prescribe Liv.52 DS as an adjuvant in
DIH, specifically in therapy with anti-TB drugs, statins,
chemotherapeutic agents, and antiretrovirals and have found
satisfactory results. Liv.52 DS exhibits hepatoprotective
properties by reducing alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) levels. When prescribed
along with anti-TB drugs, Liv.52 DS reduces the incidence
of DIH and improves patient compliance, and thus ensures
uninterrupted treatment.
The natural ingredients in Liv.52 DS exhibit potent
hepatoprotective properties against chemically-induced
hepatotoxicity. Liv.52 DS restores the functional efficiency of
the liver by protecting the hepatic parenchyma and promoting
hepatocellular regeneration.
In drug-induced hepatitis…
3
TNF-α Genetic Polymorphism -308G/A
and Antituberculosis Drug-induced
Hepatitis
Kim SH, et al
Liver Int. 2012;32(5):809–814.
While the mechanisms underlying the development of
drug-induced liver injury are not clear, there is evidence
to suggest that tumor necrosis factor-α (TNF-α) plays an
important role in drug-induced or drug metabolite-induced
immune responses. We hypothesized that polymorphisms in
the TNF-α gene are associated with anti-tuberculosis drug
(ATD)-induced hepatitis.
Patients who suffered from ATD-induced hepatitis were
enrolled in the study. ATD-induced hepatitis was defined as
an increase in liver transaminase levels that were more than 3
times the upper limit of normal. ATD-tolerant patients were
used as a control. Patients were treated with first-line ATD
therapies including isoniazid, rifampicin, ethambutol, and
pyrazinamide. We compared the genotype frequencies of the
TNF-α polymorphism -308G/A in 77 patients with ATD-
induced hepatitis and 229 ATD-tolerant patients.
The frequency of carrying the variant allele (AG or AA) was
significantly higher in patients with ATD-induced hepatitis
compared with ATD-tolerant patients (26.0% vs 15.3%, P =
.034, OR (95% CI) = 1.94 (1.04–3.64)) and the frequency of
the A allele was significantly different between the 2 groups
(0.143 vs 0.079, P = .018, OR (95% CI) = 1.95 (1.11–3.44)).
These results reveal that the TNF-α genetic polymorphism
-308G/A is significantly associated with ATD-induced
hepatitis. This genetic variant may be a risk factor for ATD-
induced hepatitis in individuals from Korea.
Herb facts
Inhibitory Effect of Solanum nigrum
on Thioacetamide-induced Liver
Fibrosis in Mice
Hsieh CC, et al
J Ethnopharmacol. 2008;119(1):117–121.
Solanum nigrum (Solanaceae) has been used in
traditional folk medicine
for its hepatoprotective
activity. The purpose
of this study was to
investigate the effects of
S nigrum extract (SNE)
on thioacetamide (TAA)-
induced liver fibrosis in
mice.
Hepatic fibrosis
was produced in mice
by administering them
with TAA (0.2 g/kg, Solanum nigrum
IP) 3 times a week for
12 weeks. Mice in the 3 TAA groups were treated daily
with distilled water and SNE (0.2 or 1.0 g/kg) through a
gastrogavage throughout the experimental period.
SNE reduced the hepatic hydroxyproline and
α-smooth muscle actin protein levels of TAA-treated
mice. SNE inhibited TAA-induced collagene (α1)(I) and
transforming growth factor-β1 (TGF-β1) mRNA levels
in the liver. Histological examination also confirmed
that SNE reduced the degree of fibrosis caused by TAA
treatment.
Oral administration of SNE significantly reduces TAA-
induced hepatic fibrosis in mice, probably through the
reduction of TGF-β1 secretion.
Solanum nigrum is used in Liv.52
®
Livline •Vol. 9 • No. 1 • Jul–Sep 2014

Loss of Appetite in
Children
Appetite is closely related
to children’s growth. Although
occasional loss of appetite is
normal in children, consistently
poor appetites can eventually
affect their health and growth and
development.

Exhibits hepatoprotective properties against drug-induced liver damage If a child is tired during
mealtime or exploring food or
Decreases ALT, AST, and normalizes ALP distracted during mealtime, it
can result in slow eating and poor
Prevents further damage to hepatic parenchyma by membrane stabilization appetite. Most children with
Reduces the incidence of drug-induced hepatitis poor appetite are picky eaters or
fussy eaters. Picky/fussy eaters
Reduces hepatotoxicity due to anti-tubercular drugs consume lesser amounts of foods
Improves patient compliance, and thus ensures uninterrupted containing vitamin E, vitamin C,
folate, and fiber, probably due to
anti-tubercular therapy lower consumption of fruits and
vegetables. Lower levels of these
specific nutrients may lead to cell
Dosage damage, immunological weakness,
Syrup/Tablet: and digestive problems. The
Drug-induced hepatitis: 1 to 2 teaspoonfuls/tablets b.i.d. with digestive problems, in particular,
anti-TB/statin/chemotherapy/antiretroviral treatment. may increase picky/fussy eating
through inappropriate associations
with foods they eat to abdominal
pains resulting from constipation.
Picky eating can be overcome
by inculcating healthy eating habits
early in life. It is observed that food
preferences that children develop
in their early years remain stable.
Research has also shown that food
preferences in children are related
to their mothers’ food choices.
It is also important to schedule
and stick to a specific snack time.
... contd from page 1 (Research update) Parents who get discouraged by
children who are picky eaters often
that could explain the DILI associated with statins. Calculation of the stop trying to give them new foods.
incidence of DILI associated with statins based on the spontaneous Laugh lines Research has shown that parents can
help their children learn to like new
reporting to SADRAC and the sale figure of statins during the study
I found a leaflet in my A young boy asked his father, foods through multiple exposures
period is shown in Table 1. Reactions were more frequent with fluvastatin
newspaper this morning which “Dad, do lawyers ever tell the (between 5 and 10) to new foods.
compared to the total study group (P < .05). Overall, a statin-related DILI
read, “Are you an alcoholic? truth?” Liv.52 drops, a
episode was reported in 1.6/100,000 person-years and in 1.2/100,000
Call now. We can help!” polyherbal
users (Table 1). The father thought for a formulation,
I called up. It was a liquor
Table 1. Statin-associated DILI According to Reports Received by SADRAC During the Study Period moment, “Yes son, sometimes a is effective in the
shop offer, “Buy 3 and get 1
lawyer will do anything to win a management of
Atorvastatin Fluvastatin Pravastatin Rosuvastatin Simvastatin Total free.”
case!” loss of appetite
No. of
••• in children. Liv.52
30 11 2 2 28 73
Reactions ••• drops normalizes the basic appetite-
A husband once complained
DDDs (x 106) 370.7 23.2 131.5 42.9 1097.8 1666.1 After digging to a depth of satiety rhythm. It also increases bile
Dear Google, secretion, restores liver function,
Person-years
10.29 0.64 3.65 1.19 30.49 46.26
100 meters last year, Russian
(x 104) Please stop behaving like my corrects metabolism, improves
scientists found traces of copper
Incidence
0.081 0.474 0.015 0.047 0.026 0.044 wife ... digestion and assimilation, increases
(x 10-6 DDDs) wire dating back 1000 years, and serum protein levels, and helps in
Incidence Will you please allow me to came to the conclusion that their weight gain. Various clinical studies
(x 10-4 2.9 17 0.5 1.6 0.9 1.6
person-years) complete the whole sentence ancestors already had a telephone have supported the benefits of
DDD, defined daily dose; DILI, drug-induced liver injury; SADRAC, Swedish Adverse Drug Reactions Advisory
before you start ...? network one thousand years ago. Liv.52 drops in improving appetite
Committee. in children.
•••
Reactions were significantly more frequent in patients taking fluvastatin (P < .05 compared to the total group).
So, not to be outdone, in the
A young woman had
weeks that followed, American
Conclusion given birth in the elevator of a
scientists dug 200 meters and Edited and Published by
hospital and was embarrassed
It was shown that although idiosyncratic liver injury associated with headlines in the US papers read,
Dr Pralhad S Patki, MD
about it. The Himalaya Drug Company, Bangalore
statins is rare, it can be associated with severe outcome. After recovery, a
“US scientists have found traces Printed at
similar pattern of liver injury can be reproduced on re-exposure. There One of the doctors, in Sri Sudhindra Offset Process
of 2000-year-old optical fibers, Bangalore
seems little doubt that certain individuals for unknown reasons may an effort to console her, said,
“Don’t feel bad. Why, only 2 and have concluded that their EDITORIAL TEAM
develop this rare side-effect.
Editor in chief
years ago a lady delivered in the ancestors already had advanced
Dr Pralhad S Patki
Atorvastatin and simvastatin are the most common statins associated high-tech digital telephone 1000
front yard of the hospital.”
with DILI, which is probably due to the fact that these are the most Managing Editor
With that the new mother years earlier than the Russians.” Dr Jayashree B Keshav
commonly used statins. Atorvastatin is mostly associated with cholestatic
liver injury whereas hepatocellular injury is more common with burst out crying. “I know,” she One week later, the Indian Editorial Assistants
Shruthi VB
simvastatin. Responsible physicians should perform liver tests in patients said, “That was me, too.” newspapers reported the Shruthi V Kumar
Janaki R Guttal
taking statins, who present with newly developed symptoms, such as, ••• following, “After digging as deep Anil Savanur
Sushma M
nausea, severe lethargy, and abdominal pain. Secret formula for married as 500 meters, Indian scientists Dhriti Akhouri

couples have found absolutely nothing. Layout Artists

Dayananda Rao S
“Love one another” They have concluded that 5000 Santosh G

years ago, their ancestors were

And if it doesn’t work, bring E-mail
the last word in the middle! already using wireless technology. publications@himalayahealthcare.com
Liv-wise

“I long to accomplish a great and noble task, but it is my chief duty

to accomplish small tasks as if they were great and noble.”
••• ••• Web Site
— Helen Keller www.himalayahealthcare.com